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Introduction
Welcome to OAN3155 Biochemistry!
Biochemistry is one of the most important basic disciplines in the formation of health care professionals, including for nursing. Both biochemistry and nursing enjoy a mutually cooperative relationship. It has illuminated aspects of health and disease.
Course Guide
Welcome to the Biochemistry Universe!
This course is designed to introduce nursing students to biochemistry via reviewing general and organic chemistry, covering the basic concepts of structures and functions of macromolecules, describing major metabolic pathways, discussing basic information of enzymes including their mechanism of actions and regulation, the cofactor essential for enzyme function and their use in clinical settings.
It is essential for nursing students to have solid knowledge of basic sciences like Biochemistry in order to understand better the biochemical processes taking place in human bodies. Nursing interventions are based on this understanding. For instance, in critical care, nurses learn how to preserve patients' energy by spreading cares throughout the day and night. Blood gasses are performed to ensure that patients’ acid- base balance and oxygenation levels are maintained to promote aerobic metabolism, aiming for short recovery period and wellbeing of the clients.
In this course guide, I will share the course learning outcomes, the overview of the plan of the course and the assessments. I will also share the expectations of being a student in this course. It is our intent to make this learning experience both convenient and fun while achieving the intended outcomes.
Course Learning Outcomes
A course learning outcome (CLO) is the expectation of what you should be able to do by the end of the course. It provides a guide to both the educator as well as the student to focus on achieving the intend outcomes. For this course, we have two course learning outcomes (CLO) that can be categorized in 1 domain; cognitive. The CLOs are as follows:
CLO 1 Explain the structure of macromolecules, their building blocks and metabolism (C2, PLO1). CLO 2 Explain the functions and mechanism involved in maintenance of water, electrolyte and acid-base balance. (C2, PLO1). Overview of Teaching and Learning Plan
As an online course, we will use the Learning Management System (LMS) for all our communication, materials and assessments. We will have synchronous meeting via the LMS as well as Self Instructional Materials (SIM) to facilitate your learning and progress through the course. As an ODL learner, you are expected to be self directed. The SIM will provide you with a complete guide of the course materials and resources. Each topic will have topic learning outcomes followed by the lesson notes. Links to videos and other resources will be provided to support your learning process. You will also be given reading materials out of the SIM. At the end of each topic, there will be self check questions. Here you can test yourself. Review the notes and resources should you need to. We will also have scheduled online meetings. Here we will have discussions and tutorials. Number of meetings: 4 two-hours online sessions.
Assessment
The assessments are planned as coursework and final examination. The breakdown of the weightage is as below:
a. Continuous Assessment
Quiz 1 10% Quiz 2 10% Test 20% b. Final Assessment
Final Examination 60%
Topic 1: Elements
1.1 Matter and element
Teaching Learning Outcome (TLO): Identify the main chemical elements of the human body.
Have you ever heard the quotes “You are what you eat?”. But do you recall eating some iodine or snacking on selenium? All forms of matter- both living and non-living are made up of a limited number of building blocks called chemical elements. Each of these elements is a substance that cannot be split into simpler substance by ordinary chemical medium. About 60 chemical elements can be found in the body, but what all of them are doing there is still unknown. Scientists believe that about 25 of the known elements are essential to life. The human body functions as a result of a large number of chemical reactions involving compounds of all these elements. In this topic we are going to discuss the chemical elements found in human body.
Matter exists in three states either liquid, solid and gas. Example of solid structure in our body is teeth, cartilage and bones. For liquid- blood and sweats, and oxygen and carbon dioxide in the lungs are the gases that can be found in our body. Let’s see which elements are use to build our body!
Human have 26 chemical elements present in our body. Among the twenty-six elements, 96% of our body mass are built on by only four elements known as the major elements. These elements are; oxygen, hydrogen, nitrogen and carbon. Eight elements known as the lesser elements contribute about 3.6% of building up the body mass that includes calcium (Ca), phosphorus (P), potassium (K), sulfur (S), sodium (Na), chlorine (Cl), magnesium (Mg) and iron (Fe). The remaining 0.4% of body mass are built by another 14 elements that is present in tiny amount known as the trace element. One example of trace element is iodine needed to make thyroid hormones.
Figure 1 Chemical Elements in the Body
1.2 Atom
TLO: Describe the structure of atoms, ions, molecules, free radicals and compounds
Now, we are diving into a deeper level. For each element, it is made up of atoms. Atom is the smallest unit of matter. Each individual atom is composed of subatomic particle. Only three types of subatomic particle are important for understanding the chemical reactions in the human body; neutron, proton and electrons.
Figure 2 Subatomic Particles. (Source: https://chem.libretexts.org/)
The nucleus of an atom is made up of positively-charged proton (p+) and uncharged neutron (n0). While the tiny, negatively-charged electron (e-) surround the nucleus. A region known as the electron shells may be depicted as simple circles around the nucleus. Each shell can hold specific number of electrons.
The first electron shell (nearest to the nucleus) only can hold two electrons. The second shell holds a maximum of eight electrons while the third one holds can hold up to 18 electrons. This diagram below will help you to understand better the electron shell model.
Figure 3 Electron Shell Model (Source: https://physics.stackexchange.com/)
The number of electrons in an atom of an element always equals the number of protons. They balanced each other charges since proton carries the positive charge while electron carries the negative charge. Hence, each atom is electrically neutral; its total charge is zero.
1.2.1 Atomic Number and Mass
The number of protons in the nucleus of an atom is an atom’s atomic number. Atoms of different elements have different atomic numbers because they have different number of protons. For example, sodium has an atomic number of 11 because its nucleus has 11 protons.
The mass number of an atom is the sum of its protons and neutrons. Since sodium has 11 protons and 12 neutrons, its mass number is 23.
Although all atoms of one element have the same number of protons, they may have different numbers of neutrons and thus different mass numbers. Atoms with the same number of protons but different numbers of neutrons are called isotopes. Therefore, isotopes have different mass numbers.
Example like carbon isotopes, some might have six neutrons, and a few have seven or eight, but all have 6 protons and 6 electrons. The isotopes commonly share the same chemical properties, but differ in physical properties. Most isotopes are stable and do not emit radiation, but some of the isotopes are unstable and emit radiation. Example of unstable isotope is the carbon-14 (C-14) that is use in determining the age of an object containing organic material (carbon-14 dating).
Figure 4 Isotopes share the same number of protons but different numbers of neutrons. (Source: https://terpconnect.umd.edu/)
Watch this video to learn more about the benefits of radioisotopes in medicine.
1.2.2 Ions, molecules, and compounds
From what we have discussed, atoms of the same elements have the same number of protons. Each atoms of the elements have a characteristic way of losing, gaining, or sharing their electrons when interacting with other atoms to achieve stability. The way the electrons behave enable atoms in the body to exist in electrically charged forms called ions, or to combine with each other and form a complex combination called molecules.
Figure 5 Illustration showing how two atoms of hydrogen and one oxygen atom forms water molecule.
An atom either loses or gains electrons in order to become an ion. An ion can either be positive or negative charge because it has unequal number of protons and electrons. Ionization is the process of losing or gaining electrons. An ion of atom is symbolized by writing its chemical symbol followed by the number of its positive (+) or negative (-) charges. For example, Na+ stands for sodium ion that has 1 positive charge because it has lost 1 electron.
Figure 6 Process of sodium ion and chloride ion forming sodium chloride (NaCl).Source: https://hugotlope.blogspot.com/
When two or more atom shares their electron, they will form a molecule. A molecular formula is a chemical formula indicating the numbers and types of atoms in a molecule. The molecular formula for a molecule of oxygen is O2. The subscript 2 indicates that the molecule contains two atoms of oxygen. Two or more different kinds of atoms may also form a molecule like in water molecule which is form by two hydrogen atoms and one atom of oxygen (H2O).
Table 1 showing the chemical formula of the compound found in everyday life.
When a substance contains atoms of two or more different elements they are called a compound. Most of the atoms in the body are joined into compounds. Any molecular species that contain an unpaired electron in their outermost shell and can exist independently is known as free radicals. Having an unpaired electron makes the free radical unstable, highly reactive, and destructive to the nearby molecules. In order to achieve stability, free radical either give up their unpaired electron or take electrons from another molecules. In doing so, free radicals might break apart or cause damage to important body molecules.
Figure 7 Illustration showing unstable free radical trying to forcefully take electrons from a healthy cell. (Source: https://clarityhorizons.wordpress.com/)
Free radicals derived from normal essential metabolic processes in the human body or from external sources such as exposure to x-rays, ozone, cigarette smoking, air pollutants and industrial chemicals. There are several diseases are linked to oxygen-derived free radicals are cancer, atherosclerosis, Alzheimer’s disease, emphysema, diabetes mellitus, cataracts and rheumatoid arthritis.
Figure 8 Illustration of how antioxidants donate its electron to the unstable free radical.
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Topic 2: Organic Compounds
TLO: Identify four types of organic molecules essential to human functioning
Organic compounds typically consist of groups of carbon atoms covalently bonded to hydrogen, usually oxygen, and often other elements as well. They are found throughout the world, in soils and seas, commercial products, and every cell of the human body. The four types most important to human structure and function are carbohydrates, lipids, proteins, and nucleic acids. Before exploring these compounds, you need to first understand the chemistry of carbon.
2.1 The chemistry of carbon
What makes organic compounds unique is the chemistry of their carbon core. Recall that carbon atoms have four electrons in their valence shell, and that the octet rule dictates that atoms tend to react in such a way as to complete their valence shell with eight electrons. Carbon atoms do not complete their valence shells by donating or accepting four electrons. Instead, they readily share electrons via covalent bonds.
Commonly, carbon atoms share with other carbon atoms, often forming a long carbon chain referred to as a carbon skeleton. When they do share, however, they do not share all their electrons exclusively with each other. Rather, carbon atoms tend to share electrons with a variety of other elements, one of which is always hydrogen. Carbon and hydrogen groupings are called hydrocarbons.
Also attached to the carbon skeleton are distinctive functional groups. A functional group is a group of atoms linked by strong covalent bonds that determine the chemical behavior of any particular compounds.
Figure 1 Major functional group of organic materials.
Small organic molecules can combine into very large molecules that are called macromolecules. Macromolecules are usually polymers. A polymer is a large molecule formed by the covalent bond of either identical or similar small building-block molecules called monomers.
Molecules that have the same molecular formula but different structures are called isomers. For instance, the molecular formulas for the sugars glucose and fructose are both C6H12O6. Due to certain individual atoms positioned differently along the carbon skeleton giving them sugars different chemical properties.
Figure 2 Glucose and fructose are considered to be isomers because they share the same molecular formula but certain individual atoms are positioned differently. (source: https://www.vedantu.com/)
Topic 3: Inorganic Compounds
3.1 Organic versus Inorganic Compound
TLO 1: Compare and contrast inorganic and organic compounds.
Most of the chemicals in your body exist in the form of compounds. Biologists and chemists divide these compounds into two principal classes: inorganic compounds and organic compounds.
- An inorganic compound is a substance that does not contain both carbon and hydrogen. A great many inorganic compounds do contain hydrogen atoms, such as water (H2O) and the hydrochloric acid (HCl) produced by your stomach. In contrast, only a handful of inorganic compounds contain carbon atoms. Carbon dioxide (CO2) is one of the few examples.
- An organic compound, then, is a
substance that contains both carbon and hydrogen. Organic compounds are
synthesized via covalent bonds within living organisms, including the
human body. Recall that carbon and hydrogen are the second and third most
abundant elements in your body. You will soon discover how these two
elements combine in the foods you eat, in the compounds that make up your
body structure, and in the chemicals that fuel your functioning.
Figure 1 Examples of organic and inorganic compounds. (source: https://sciencenotes.org/)
3.2 Properties of water
TLO 2: Identify the characteristic of water that makes it essential for life
The adult’s body are composed as much as 70% of water. Water is the most important and abundant inorganic compound in all living systems. We might be able to survive without food for a week, but without water we would die in matter of days. Nearly all the body’s chemical reactions occur in a watery medium.
3.2.1 Water as solvent
A mixture is a combination of two or more substances, each of which maintains its own chemical identity. In other words, the constituent substances are not chemically bonded into a new, larger chemical compound. The concept is easy to imagine if you think of powdery substances such as flour and sugar; when you stir them together in a bowl, they obviously do not bond to form a new compound. The room air you breathe is a gaseous mixture, containing three discrete elements—nitrogen, oxygen, and argon—and one compound, carbon dioxide. There are three types of liquid mixtures, all of which contain water as a key component. These are solutions, colloids, and suspensions.
For cells in the body to survive, they must be kept moist in a water-based liquid called a solution. In chemistry, a liquid solution consists of a solvent that dissolves a substance called a solute. An important characteristic of solutions is that they are homogeneous; that is, the solute molecules are distributed evenly throughout the solution. If you were to stir a teaspoon of salt into a glass of water, the salt would dissolve into salt molecules separated by water molecules. The ratio of salt to water in the left side of the glass would be the same as the ratio of salt to water in the right side of the glass. If you were to add more salt, the ratio of salt to water would change, but the distribution—provided you had stirred well—would still be even.
Figure 2 Solute, solvent and solution (source: https://thechemistrynotes.com/)
Water is considered the “universal solvent” and it is believed that life cannot exist without water because of this. Water is certainly the most abundant solvent in the body; essentially all of the body’s chemical reactions occur among compounds dissolved in water.
Because water molecules are polar, with regions of positive and negative electrical charge, water readily dissolves ionic compounds and polar covalent compounds. Such compounds are referred to as hydrophilic, or “water-loving.” As mentioned above, salt dissolves well in water. This is because salt molecules contain regions of hydrogen-oxygen polar bonds, making it hydrophilic. Nonpolar molecules, which do not readily dissolve in water, are called hydrophobic, or “water-fearing.”
The ability of water to form solutions is essential to health and survival. Because water can dissolve so many different substances, it is an ideal medium for metabolic reactions. Water enables dissolved reactants to collide and form products. Water also dissolves waste products, which allows them to be flushed out of the body in the urine.
3.2.2 Water in chemical reactions
Water serves as the medium for most chemical reactions in the body and participates as a reactant or product in certain reactions. During digestion, for example, decomposition reactions break down large nutrient molecules into smaller molecules by the addition of water molecules. This process is known as the hydrolysis.
Hydrolysis reactions enable dietary nutrients to be absorbed into the body. By contrast, when two smaller molecules join to form a larger molecule in a dehydration synthesis reaction (de- = from, down, or out; hydra- = water), a water molecule is one of the products formed.
Figure 3 Dehydration and hydrolysis process that either use or produce water. (source: https://openstax.org/)
Topic 4: Carbohydrates-Structure & Functions
TLO: Identify the building blocks of carbohydrates.
Carbon, hydrogen and oxygen are the elements found in carbohydrates. The ratio of hydrogen to oxygen atoms is usually 2:1, the same as in water. Although there are exceptions, carbohydrates generally contain one water molecule for each carbon atom. This is the reason why they are called carbohydrates which means “watered carbon”. Carbohydrates include sugar, glycogen, starches and cellulose. They only represent about 2-3% of body mass. In human and animal, carbohydrate functions mainly as a source of chemical energy for generating ATP needed for metabolic reactions.
There are three major groups of carbohydrates, based on their sizes including monosaccharides, disaccharides and polysaccharides.
4.1 Monosaccharides and disaccharides
Monosaccharides and disaccharides are known as simple sugars. Monosaccharides, the monomers of carbohydrates contain from three to seven carbon atoms. They are designated by suffices “-ose” at the end and prefix that indicates the number of the carbon atoms. For example, monosaccharides with three carbons are called trioses (three-carbon sugar). There are also tetroses (four-carbon sugar), pentoses (five-carbon sugar), hexoses (six-carbon sugar) and heptoses (seven-carbon sugar). Cells throughout our body utilize hexose glucose to produce ATP. Example of triose, pentose and hexoses sugar are shown in the following diagram.
Figure 1 Sugar are varied in structures even they have same numbers of carbon. Yet another difference can come in their reactive group on the end, being either ketone (ketoses) or aldehyde group (aldoses).
A disaccharide is a molecule formed from the combination of two monosaccharides by dehydration synthesis. For example, molecules of the monosaccharides glucose and galactose combine to form a molecule of the disaccharide lactose.
Figure 2 Molecules of monosaccharide galactose and glucose forms the disaccharide lactose.
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Topic 5: Carbohydrate Metabolism
TLO: Define metabolism.
Metabolism (me-TAB-oˉ-lizm; metabol- = change) refers to all of the chemical reactions that occur in the body. There are two types of metabolism: catabolism and anabolism. Those chemical reactions that break down complex organic molecules into simpler ones are collectively known as catabolism (ka-TAB-oˉ-lizm; cata- = downward). Overall, catabolic (decomposition) reactions are exergonic; they produce more energy than they consume, releasing the chemical energy stored in organic molecules. Important sets of catabolic reactions occur in glycolysis, the Krebs cycle, and the electron transport chain, each of which will be discussed later in the chapter.
Chemical reactions that combine simple molecules and monomers to form the body’s complex structural and functional components are collectively known as anabolism (a-NAB-oˉ-lizm; ana- = upward). Examples of anabolic reactions are the formation of peptide bonds between amino acids during protein synthesis, the building of fatty acids into phospholipids that form the plasma membrane bilayer, and the linkage of glucose monomers to form glycogen. Anabolic reactions are endergonic; they consume more energy than they produce.
Metabolism is an energy-balancing act between catabolic (decomposition) reactions and anabolic (synthesis) reactions. The molecule that participates most oft en in energy exchanges in living cells is ATP (adenosine triphosphate), which couples energy-releasing catabolic reactions to energy-requiring anabolic reactions.
Watch this video about carbohydrate metabolism.
Topic 6: Lipid-Structure and Function
TLO: Identify the different types of lipids.
Do you still remember about the cell membrane structure that you have learned from Anatomy and Physiology? Do recall, the main structure of our cellular membrane is made of phospholipid—which is made of lipid or also known as fat. Due to its water-insolubility properties, this give them the ability to control what comes in and out of the cell—thus, achieving homeostasis.
Let’s get to know more about lipid. Lipids are fatty, waxy, or oily compounds that are soluble in organic solvents and insoluble in polar solvents such as water. Lipid is the second most important group of organic compounds in the body. It makes up 18-25% of body mass in lean adults. Similar like carbohydrate, lipids also contain carbon, hydrogen, nitrogen and oxygen. The difference between these two organic compounds is the lipid do not have a 2:1 ratio of hydrogen to oxygen.
Most lipids are hydrophobic which means they are insoluble in polar solvent like water. They are non-polar—meaning that the charge distribution is evenly distributed and the molecules does not have positive or negative charge ends. As a result of their hydrophobic nature, only the smallest lipids (some fatty acids) can dissolve in watery blood plasma. In order to become more soluble in plasma, other lipid molecules join with hydrophilic protein molecules resulting in a formation of lipid-protein complexes known as lipoprotein. Lipoproteins are soluble because the lipid is coated by protein from outside.
Figure 1 Lipoprotein is soluble in plasma because inner hydrophobic core is coated by protein.
Topic 7: Lipid Metabolism
TLO: Discuss the fate, metabolism, and functions of lipids.
The Fate of Lipids
Lipids, like carbohydrates, may be oxidized to produce ATP. If the body has no immediate need to use lipids in this way, they are stored in adipose tissue (fat depots) throughout the body and in the liver. A few lipids are used as structural molecules or to synthesize other essential substances. Some examples include phospholipids, which are constituents of plasma membranes; lipoproteins, which are used to transport cholesterol throughout the body; thromboplastin, which is needed for blood clotting; and myelin sheaths, which speed up nerve impulse conduction. Two essential fatty acids that the body cannot synthesize are linoleic acid and linolenic acid. Dietary sources include vegetable oils and leafy vegetables. The various functions of lipids in the body may be reviewed in table below.
Triglyceride storage
A major function of adipose tissue is to remove triglycerides from chylomicrons and VLDLs and store them until they are needed for ATP production in other parts of the body. Triglycerides stored in adipose tissue constitute 98% of all body energy reserves. They are stored more readily than glycogen, in part because triglycerides are hydrophobic and do not exert osmotic pressure on cell membranes. Adipose tissue also insulates and protects various parts of the body.
Adipocytes in the subcutaneous layer contain about 50% of the stored triglycerides. Other adipose tissues account for the other half: about 12% around the kidneys, 10–15% in the omentum, 15% in genital areas, 5–8% between muscles, and 5% behind the eyes, in the sulci of the heart, and attached to the outside of the large intestine. Triglycerides in adipose tissue are continually broken down and resynthesized. Thus, the triglycerides stored in adipose tissue today are not the same molecules that were present last month because they are continually released from storage, transported in the blood, and redeposited in other adipose tissue cells.
Lipid catabolism: Lipolysis
In order for muscle, liver, and adipose tissue to oxidize the fatty acids derived from triglycerides to produce ATP, the triglycerides must first be split into glycerol and fatty acids, a process called lipolysis. Lipolysis is catalysed by enzymes called lipases. Epinephrine and norepinephrine enhance triglyceride breakdown into fatty acids and glycerol. These hormones are released when sympathetic tone increases, as occurs, for example, during exercise.
Other lipolytic hormones include cortisol, thyroid hormones, and insulin-like growth factors. By contrast, insulin inhibits lipolysis. The glycerol and fatty acids that result from lipolysis are catabolized via different pathways. Glycerol is converted by many cells of the body to glyceraldehyde 3-phosphate, one of the compounds also formed during the catabolism of glucose. If ATP supply in a cell is high, glyceraldehyde 3-phosphate is converted into glucose, an example of gluconeogenesis. If ATP supply in a cell is low, glyceraldehyde 3-phosphate enters the catabolic pathway to pyruvic acid.
Fatty acids are catabolized differently than glycerol and yield more ATP. The first stage in fatty acid catabolism is a series of reactions, collectively called beta oxidation, that occurs in the matrix of mitochondria. Enzymes remove two carbon atoms at a time from the long chain of carbon atoms composing a fatty acid and attach the resulting two-carbon fragment to coenzyme A, forming acetyl CoA. Then, acetyl CoA enters the Krebs cycle. A 16-carbon fatty acid such as palmitic acid can yield as many as 129 ATPs on its complete oxidation via beta oxidation, the Krebs cycle, and the electron transport chain.
As part of normal fatty acid catabolism, hepatocytes can take two acetyl CoA molecules at a time and condense them to form acetoacetic acid. This reaction liberates the bulky CoA portion, which cannot diff use out of cells. Some acetoacetic acid is converted into beta-hydroxybutyric acid and acetone. The formation of these three substances, collectively known as ketone bodies, is called ketogenesis. Because ketone bodies freely diff use through plasma membranes, they leave hepatocytes and enter the bloodstream.
Other cells take up acetoacetic acid and attach its four carbons to two coenzyme A molecules to form two acetyl CoA molecules, which can then enter the Krebs cycle for oxidation. Heart muscle and the cortex (outer part) of the kidneys use acetoacetic acid in preference to glucose for generating ATP. Hepatocytes, which make acetoacetic acid, cannot use it for ATP production because they lack the enzyme that transfers acetoacetic acid back to coenzyme A.
Lipid anabolism: Lipogenesis
Liver cells and adipose cells can synthesize lipids from glucose or amino acids through lipogenesis, which is stimulated by insulin. Lipogenesis occurs when individuals consume more calories than are needed to satisfy their ATP needs. Excess dietary carbohydrates and fats all have the same fate—they are converted into triglycerides. Certain amino acids can undergo the following reactions: amino acids → acetyl CoA → fatty acids → triglycerides. The use of glucose to form lipids takes place via two pathways: (1) glucose → glyceraldehyde 3-phosphate → glycerol and (2) glucose → glyceraldehyde 3-phosphate→ acetyl CoA → fatty acids. The resulting glycerol and fatty acids can undergo anabolic reactions to become stored triglycerides, or they can go through a series of anabolic reactions to produce other lipids such as lipoproteins, phospholipids, and cholesterol.
Watch this video to help you understand better about lipid metabolism.
Topic 8: Amino Acids- Structure and Functions
TLO 1: Identify the building blocks of proteins.
Proteins are large molecules that contain carbon, hydrogen, oxygen, and nitrogen. Some proteins also contain sulphur. A normal, lean adult body is 12–18% protein. Much more complex in structure than carbohydrates or lipids, proteins have many roles in the body and are largely responsible for the structure of body tissues. Enzymes are proteins that speed up most biochemical reactions. Other proteins work as “motors” to drive muscle contraction. Antibodies are proteins that defend against invading microbes. Some hormones that regulate homeostasis also are proteins.
The monomers of proteins are amino acids. Each of the 20 different amino acids has a hydrogen (H) atom and three important functional groups attached to a central carbon atom: (1) an amino group (-NH2), (2) an acidic carboxyl group (-COOH), and (3) a side chain (R group). At the normal pH of body fluids, both the amino group and the carboxyl group are ionized. The different side chains give each amino acid its distinctive chemical identity.
A protein is synthesized in stepwise fashion—one amino acid is joined to a second, a third is then added to the first two, and so on. The covalent bond joining each pair of amino acids is a peptide bond. It always forms between the carbon of the carboxyl group (-COOH) of one amino acid and the nitrogen of the amino group (-NH2) of another. As the peptide bond is formed, a molecule of water is removed, making this a dehydration synthesis reaction. Breaking a peptide bond, as occurs during digestion of dietary proteins, is a hydrolysis reaction.
When two amino acids combine, a dipeptide form. Adding another amino acid to a dipeptide produces a tripeptide. Further additions of amino acids result in the formation of a chainlike peptide (4–9 amino acids) or polypeptide (10–2000 or more amino acids). Small proteins may consist of a single polypeptide chain with as few as 50 amino acids. Larger proteins have hundreds or thousands of amino acids and may consist of two or more polypeptide chains folded together. Because each variation in the number or sequence of amino acids can produce a different protein, a great variety of proteins is possible. The situation is similar to using an alphabet of 20 letters to form words. Each different amino acid is like a letter, and their various combinations give rise to a seemingly endless diversity of words (peptides, polypeptides, and proteins).
TLO 2: Describe the different classification of proteins structurally and morphologically.
Structural level of protein
Proteins exhibit four levels of structural organization. The primary structure is the unique sequence of amino acids that are linked by covalent peptide bonds to form a polypeptide chain. A protein’s primary structure is genetically determined, and any changes in a protein’s amino acid sequence can have serious consequences for body cells. In sickle cell disease, for example, a nonpolar amino acid (valine) replaces a polar amino acid (glutamate) through two mutations in the oxygen-carrying protein haemoglobin. This change of amino acids diminishes haemoglobin’s water solubility. As a result, the altered haemoglobin tends to form crystals inside red blood cells, producing deformed, sickle-shaped cells that cannot properly squeeze through narrow blood vessels.
The secondary structure of a protein is the repeated twisting or folding of neighbouring amino acids in the polypeptide chain. Two common secondary structures are alpha helixes (clockwise spirals) and beta pleated sheets. The secondary structure of a protein is stabilized by hydrogen bonds, which form at regular intervals along the polypeptide backbone.
The tertiary structure refers to the three-dimensional shape of a polypeptide chain. Each protein has a unique tertiary structure that determines how it will function. The tertiary folding pattern may allow amino acids at opposite ends of the chain to be close neighbours. Several types of bonds can contribute to a protein’s tertiary structure. The strongest but least common bonds, S⏤S covalent bonds called disulfide bridges, form between the sulfhydryl groups of two monomers of the amino acid cysteine. Many weak bonds—hydrogen bonds, ionic bonds, and hydrophobic interactions— also help determine the folding pattern.
In those proteins that contain more than one polypeptide chain (not all of them do), the arrangement of the individual polypeptide chains relative to one another is the quaternary structure. Proteins vary tremendously in structure. Different proteins have different architectures and different three-dimensional shapes. This variation in structure and shape is directly related to their diverse functions.
Figure 1 Structural level of protein (source: https://www.onlinebiologynotes.com/level-of-structural-organization-of-protein/)
Morphological classification of protein
On the basis of overall shape, proteins are classified as fibrous or globular.
Fibrous proteins are insoluble in water and their polypeptide chains form long strands that are parallel to each other. Fibrous proteins have many structural functions. Examples include collagen (strengthens bones, ligaments, and tendons), elastin (provides stretch in skin, blood vessels, and lung tissue), keratin (forms structure of hair and nails and waterproofs the skin), dystrophin (reinforces parts of muscle cells), fibrin (forms blood clots), and actin and myosin (are involved in contraction of muscle cells, division in all cells, and transport of substances within cells).
Globular proteins are more or less soluble in water and their polypeptide chains are spherical (globular) in shape. Globular proteins have metabolic functions. Examples include enzymes, which function as catalysts; antibodies and complement proteins, which help protect us against disease; haemoglobin, which transports oxygen; lipoproteins, which transport lipids and cholesterol; albumins, which help regulate blood pH; membrane proteins, which transport substances into and out of cells; and some hormones such as insulin, which helps regulate blood sugar level.
Figure 2 Fibrous protein forms long strands that are parallel to each other while globular protein is spherical in shape. (source: https://ib.bioninja.com.au/standard-level/topic-2-molecular-biology/24-proteins/fibrous-vs-globular-protein.html)
TLO 3: Describe the functional roles of proteins.
This table below describes the functional roles of proteins.
Topic 9:Amino Acids Metabolism
TLO: Describe the metabolism of proteins
During digestion, proteins are broken down into amino acids. Unlike carbohydrates and triglycerides, which are stored, proteins are not warehoused for future use. Instead, amino acids are either oxidized to produce ATP or used to synthesize new proteins for body growth and repair. Excess dietary amino acids are not excreted in the urine or faeces but instead are converted into glucose (gluconeogenesis) or triglycerides (lipogenesis).
Protein Catabolism
A certain amount of protein catabolism occurs in the body each day, stimulated mainly by cortisol from the adrenal cortex. Proteins from worn-out cells (such as red blood cells) are broken down into amino acids. Some amino acids are converted into other amino acids, peptide bonds are re-formed, and new proteins are synthesized as part of the recycling process. Hepatocytes convert some amino acids to fatty acids, ketone bodies, or glucose. Cells throughout the body oxidize a small amount of amino acids to generate ATP via the Krebs cycle and the electron transport chain. However, before amino acids can be oxidized, they must first be converted to molecules that are part of the Krebs cycle or can enter the Krebs cycle, such as acetyl CoA.
Before amino acids can enter the Krebs cycle, their amino group (NH2) must first be removed—a process called deamination. Deamination occurs in hepatocytes and produces ammonia (NH3). The liver cells then convert the highly toxic ammonia to urea, a relatively harmless substance that is excreted in the urine.
Figure 1 Deamination process refers to the process of removing the amine group of the amino acid
The conversion of amino acids into glucose (gluconeogenesis) and into fatty acids (lipogenesis) or ketone bodies (ketogenesis) may be reviewed in the figure below. Gluconeogenesis is the formation of glucose from non-carbohydrate sources that usually happens during fasting, low-carb diets, intense exercise and starvation which utilize amino acids (mainly alanine and glutamine), lactate or glycerol and converts it into glucose molecule. The gluconeogenesis pathway mainly is reversal of the steps in glycolysis (the process to breakdown glucose).
Figure 2 The process of gluconeogenesis is the reversal with the glycolysis process. (source: https://step1.medbullets.com/biochemistry/102052/gluconeogenesis)
Watch this video to understand amino acids metabolism
Topic 10: Enzymes- Part I
TLO 1: Define enzymes, proenzymes and cofactors.
Enzymes play an essential role in each living cell of our body—whether they are organs, muscles, bones, nerves etc. Without enzymes our body would not function at all. Try to recall back all the processes that we have discussed so far—carbohydrate metabolism, lipid metabolism and protein metabolism. All of these metabolism (either anabolic or catabolic) uses enzymes to produce products.
Enzymes are biological catalyst produced by living tissues. A catalyst is a substance that help to speed up chemical reactions in our body without itself undergoing any permanent chemical changes. They speed up chemical reactions by lowering the activation energy needed to start the process.
Figure 1 Enzyme work as a catalyst that speeds up chemical reaction by lowering the activation energy (source: https://wou.edu/chemistry/courses/online-chemistry-textbooks/ch450-and-ch451-biochemistry-defining-life-at-the-molecular-level/chapter-7-catalytic-mechanisms-of-enzymes/)
Some enzymes consist of two parts—a protein portion known as the apoenzyme and a non-protein portion known as the cofactors. Cofactor is an additional component that helps to optimize the enzyme’s activity. It may be organic compounds called coenzymes or it may be inorganic ions called activators. There are many vitamins that function as coenzymes. The list of coenzymes and activators are given in the table below.
Table 1 List of coenzymes with its function.
Table 2 List of activators and the enzymes they activating
A number of enzymes found in the blood or digestive tract are present in precursor or inactivated enzyme known as the proenzymes. Precursor proteins or inactive enzyme names have the prefix “pro-” like prothrombin, proelastase etc. or suffix “-ogen” like trypsinogen, chymotrypsinogen, pepsinogen etc.
TLO 2: Describe the general properties of enzymes
Enzymes catalyze specific reactions. They do so with great efficiency and with many built-in controls. There are three important properties of enzymes that includes:
Enzymes are highly specific
Each particular enzyme binds only to specific substrates (the reactant molecules on which the enzyme acts). There are more than 1,000 known enzymes in our body, each has a characteristic three-dimensional shape with specific surface configuration allowing it to recognize and bind to certain substrates. In certain cases, the part of the enzyme that catalyzes the reactions known as active site is thought to fit the substrate like a key fit in a lock (Lock and Key Model suggested by Emil Fisher). On the other hand, the active sites change its shape to fit adequately around the substrates once the substrates enter the active site. This change is known as the induced fit (Induced-fit model suggested by Daniel E. Koshland).
Figure 2 Diagram showing lock and key model of enzyme action suggested by Fisher (source://saylordotorg.github.io/)
Figure 3 Induced-fit model of enzyme action suggested by Koshland (source: //thebiologynotes.com/)
Enzymes are very efficient
Under optimal conditions, enzymes are able to catalyze reactions that are ranging from 100 million to 10 billion times more rapid than those of similar reactions without enzymes. The number of substrate molecules that a single enzyme can convert into product molecules in one second is generally between 1 and 10,000 and can be as high as 600,000.
Enzymes are subject to a variety of cellular controls
Their rate of synthesis and their concentration at any given time are under the control of a cell’s genes. Substances within the cell may either enhance or inhibit the activity of a given enzyme. Many enzymes have both active and inactive forms in cells. The rate at which the inactive form becomes active or vice versa is determined by the chemical environment inside the cell.
Figure 4 Multiple factors that can enhance or inhibit enzyme activity
TLO 3: List the different classification of enzymes
According to the International Union of Biochemistry (IUB), enzymes are classified into six major classifications as follows:
1. Oxireductases
2. Transferases
3. Hydrolases
4. Lyases
5. Isomerases
6. Ligases
Oxireductases
Group of enzymes that catalyze oxidation-reduction reactions are included in this class which can be illustrated as follows:
Oxidation is the process of electron loss during a reaction by molecule, atom or ion. The opposite process is called as reduction which means the molecule, atom or ion gains electron during a reaction.
Enzymes in this category include:
- Dehydrogenases
- Reductases
- Oxidases
- Peroxidases
Specific example:
This reaction is the conversion of lactate to pyruvate. Lactate or lactic acid is the result of anaerobic (absence of oxygen) respiration. Once the oxygen supply replenish, lactate will convert back to pyruvate by lactate dehydrogenase enzyme.
Transferases
Group of enzymes that catalyze the transfer of a functional group like amino, carboxyl, methyl or phosphoryl etc. from one molecule to another. The reactions can be illustrated as below:
Some common enzymes grouped under this category includes:
- Amino transferase or transaminase
- Kinase
- Transcarboxylase
Specific example:
Alanine aminotransferase (ALT) also formerly known as glutamate pyruvate transaminase (GPT) is an enzyme catalyzing the conversion process of alanine into pyruvate for cellular energy production. During this conversion process, amino group from alanine transfers to α-ketoglutarate molecules, forming pyruvate and glutamate. The process is illustrated as below:
Topic 11: Enzymes-Part II
TLO 1: Describes how an enzyme works.
Enzymes lower the activation energy of a chemical reaction by decreasing the “randomness” of the collisions between molecules. They also help bring the substrates together in the proper orientation so that the reaction can occur. The process includes:
- The substrates contact the active site on the surface of the enzyme molecule, forming a temporary intermediate compound called the enzyme–substrate complex. In this reaction the two substrate molecules are sucrose (a disaccharide) and water.
- The substrate molecules are transformed by the rearrangement of existing atoms, the breakdown of the substrate molecule, or the combination of several substrate molecules into the products of the reaction. Here the products are two monosaccharides: glucose and fructose.
- After the reaction is completed and the reaction products move away from the enzyme, the unchanged enzyme is free to attach to other substrate molecules.
Figure 1 Illustration showing enzyme action (source: Tortora Textbook)
TLO 2: Describe the factors regulating enzyme activity
As we have concluded before, there are several factors that can enhance or inhibit the enzyme action.
Effect of substrate concentration
For a given quantity of enzyme, the velocity of the reaction increases as the concentration of the substrate is increased. Increasing substrate concentration cause increase rate of reaction until the active site of enzymes are used.
Figure 2 The effect of substrate concentration on enzyme action (source: //www.geeksforgeeks.org)
Effect of Enzyme Concentration
The velocity of a reaction is directly proportional to the amount of enzyme present as long as the amount of substrate is not limiting. The substrate must be present at a concentration sufficient to ensure that all of the enzyme molecules have substrate bound to their active site.
Figure 3 The relationship between enzyme concentration and rate of reaction
Effect of pH (concentration of hydrogen ions)
Each enzyme has an optimum pH, i.e. a pH at which the enzyme activity is maximum. Below or above this pH, enzyme activity is decreased. The optimum pH differs from enzyme to enzyme, for example optimum pH for pepsin is 1.2 (acidic) while for trypsin is 8.0 (alkaline).
Figure 4 Effects of pH on enzyme action
Effects of temperature
Enzyme catalysed reactions show an increase in rate with increasing temperature only within a relatively small and low temperature range. Each enzyme shows the highest activity at a particular temperature called optimum temperature. The activity progressively declines both above and below this temperature. Increase in velocity is due to the increase in the kinetic energy. Further elevation of the temperature results in a decrease in reaction velocity due to denaturation of the enzyme protein.
Figure 5 Effects of temperature on enzyme action
Effect of end-products
Accumulation of products of the reaction causes the inhibition of enzyme activity for some enzymatic reactions, this form of control will limit the rate of formation of the product when the product is under used. In biological systems, however, the product is usually removed as it becomes a substrate for a succeeding enzyme in a metabolic pathway.
Effect of activators and co-enzymes
The activity of many enzymes is dependent on the activators (metallic ions) like Mg2+, Mn2+, Zn2+, Ca2+, Co2+, Cu2+, etc. and coenzymes for their optimum activity. In absence of these activators and coenzymes, enzymes become functionally inactive.
Effect of time
Under optimum conditions of pH and temperature, time required for an enzyme reaction is less. The time required for the completion of an enzyme reaction increases with changes in temperature and pH from its optimum.
Effect of physical agent
Physical agent like light rays can inhibit or accelerate certain enzyme reactions. For example, the activity of salivary amylase is increased by red and blue light. On the other hand, it is inhibited by ultraviolet rays.
Effect of inhibitors
The substances which stop the enzymatic reaction are called inhibitors. Presence of these substances in reaction medium decreases the rate of enzyme reaction. Any substance that can diminish the velocity of an enzyme catalysed reaction is called inhibitor. Two general classes of inhibitors are recognized according to whether the inhibitor action is reversible or irreversible:
- Reversible inhibitor
- Irreversible inhibitor
Figure 6 Classification of enzyme inhibitors
Reversible inhibitor
Reversible inhibitors bind to enzymes through noncovalent bonds and the activity of the enzyme is restored fully when the inhibitor is removed from the system.
Figure 7 Mechanism of enzyme inhibitors
Different types of reversible inhibitors are:
- Competitive inhibitor
A competitive inhibitor is usually a structurally similar of the substrate. But because it is not identical with the substrate, breakdown into products does not take place. When both the substrate and this type of inhibitor are present, they compete for the same binding site on the enzyme.One of the examples of drug that inhibit enzymes as their mechanism of action is sulphonamide. Sulphonamide is an analogue of P-aminobenzoic acid (PABA) and inhibits pteroid synthetase enzyme required for the synthesis of folic acid in microorganisms. Many drugs which act as competitive inhibitors are given below:
2. Non-competitive inhibitorAs the name implies, in this type of inhibition no competition occurs between substrate and inhibitor. Inhibitor is usually structurally different from the substrate. It binds at a site on the enzyme molecule other than the substrate-binding site and thus there is no competition between inhibitor and substrate. Examples of non-competitive inhibitors are:
- Ethanol or certain narcotic drugs are non-competitive inhibitor of acid phosphatase.
- Trypsin inhibitors occur in soybean and raw egg white, inhibit activity of trypsin noncompetitively.
- As well as Ascaris parasites (worm) contain pepsin and trypsin inhibitors, which inhibit noncompetitively action of pepsin and trypsin, that is why ascaris worm is not digested in human intestine.
Irreversible inhibitors
An irreversible inhibitor binds with an enzyme tightly covalently and forms a stable complex. An irreversible inhibitor cannot be released by dilution or dialysis or simply by increasing the concentration of substrate. Irreversible inhibitors can be further subdividing into three:
- Group Specific Inhibitor
These inhibitors react with specific R-groups (side chain) of amino acid residues in the active site of enzyme. Examples of medication that works through this mechanism is:
Di-isopropylphosphofluoride (DIPF): DIPF can inhibit an enzyme acetylcholine esterase by covalently reacting with hydroxyl group of a serine residue present at the active site of the enzyme. DIPF is a parasympathomimetic drug, irreversibleanti-cholinesterase inhibitors and has been used locally in the oily eye drops in glaucoma treatment.
2. Substrates Analogue Irreversible Inhibitor
Substrate analogues or affinity labels are molecules that are structurally similar to the substrate. These substrate analogues possess a highly reactive group which is not present in the natural substrate. The reactive group of substrate analogues covalently reacts with amino acid residues of the active site of the enzyme and permanently block the active site of the enzyme.
3. Suicide Inhibitor
These compounds are relatively unreactive until they bind to the active site of a specific enzyme. On binding to the active site of the enzyme they carry out the first few catalytic activities of the normal enzyme reaction. Instead of being transformed into a normal product, however, the inhibitor is converted to a very reactive compound that combines irreversibly with the enzyme leading to its irreversible inhibition. The enzyme literally commits suicide. Some drugs that works through this mechanism are:
Penicillin: Penicillin irreversibly inactivates an essential bacterial enzyme glycopeptidyl transpeptidase involved in the formation of bacterial cell wall.
Aspirin: Aspirin inactivates an enzyme cyclo-oxygenase which catalyzes the first reaction in the biosynthesis of prostaglandins from arachidonic acid.
Topic 12: Vitamins
TLO: List the common vitamins and their sources and the problems associated with a deficit or excess
Introduction
Vitamins are organic nutrients that are required in small quantities (in micrograms to milligram quantities per day) for a variety of biochemical functions and which generally cannot be synthesized by the body and must, therefore, be supplied by the diet. Some of the vitamin can be synthesized by the intestinal microorganisms, but in quantities that does not meet our need sufficiently. Do recall the lesson from previous chapter about enzymes, many vitamins act as coenzymes whereby the combination of these vitamins with certain enzymes optimizes the enzyme activity for example formation of clotting proteins requires the presence of vitamin K.
Figure 1 Vitamin acts as coenzyme to either activate or optimize the enzyme reaction. (source: www.pharmaguideline.com)
The vitamins are grouped into two categories based on their solubility:
Water soluble vitamins: absorbed with water along digestive tract, cannot be stored, any excess will be excreted in urine. Example of water-soluble vitamins are thiamine, riboflavin, biotin, niacin, folic acid, cyanocobalamin and ascorbic acid.
Fat soluble vitamins: combine with lipids and can be stored in the body (except for vitamin K). Since they can be stored in our adipose tissue, they have high risk of forming vitamin toxicity when accumulated. Example of fat-soluble vitamins are retinol (vitamin A), cholecalciferol (vitamin D), tocopherol (vitamin E) and phylloquinone (vitamin K).
Table 1 showing the common properties of fat-soluble and water-soluble vitamins
FAT-SOLUBLE VITAMINS
Vitamin A
Chemistry
Vitamin A consists of three biologically active molecules which are collectively known as retinoids. Common form of vitamin A is retinol, retinal and retinoic acid. Each of these compounds are derived from the plant precursor molecule, β-carotene (also known as carotenoids).
Sources
The richest dietary sources of vitamin A are fish liver oils (cod liver oil). Animal’s liver are also rich sources but meat is rather low in vitamin A. Other good sources are milk and dairy products, dark green leaves, such as spinach and yellow and red fruits and vegetables, such as carrots, tomatoes, and peaches. The table below summarise the sources of vitamin A
Functions
Different forms of the vitamin have different functions.
– Retinal and retinol are involved in vision.
– Retinoic acid is involved in cellular differentiation and metabolic processes.
– β-carotene is involved in antioxidant function.
The recommended daily allowance (RDA) of vitamin A for adults is 800–1000 retinol equivalents. (1 retinol equivalent = 1 µg retinol = 6 µg β-carotene).
Deficiency manifestations
Effect on vision: night blindness also known as nyctalopia. Night blindness is one of the earliest symptoms of vitamin A deficiency. This is characterized by loss of vision in night (in dim or poor light) since dark adaptation time is increased. Prolonged deficiency of vitamin A leads to an irreversible loss of visual cells. Severe vitamin A deficiency causes dryness of cornea and conjuctiva, a clinical condition termed as xerophthalmia (dry eyes). If this situation prolongs, keratinization and ulceration of cornea takes place. This results in destruction of cornea. The cornea becomes totally opaque resulting in permanent loss of vision (blindness), a clinical condition termed as keratomalacia. Xerophthalmia and keratomalacia are commonly observed in children. White opaque spots develop on either side of cornea in vitamin A deficiency are known as Bitot’s spot.
Figure 2 The difference between normal night vision and night blindness
Figure 3 Bitot’s spot can be seen on the sclera. (source: https://www.cmaj.ca/content/189/40/E1264)
Effect on skin: Vitamin A deficiency causes keratinization of epithelial cells of skin which leads to keratosis of hair follicles, and dry, rough and scaly skin. Keratinization of epithelial cells of respiratory, urinary tract makes them susceptible to infections.
Other symptoms of vitamin A deficiency: Failure of growth in children, faulty bone modelling producing thick cancellous (spongy) bones instead of thinner and more compact ones, abnormalities of reproduction, including degeneration of the testes, abortion or the production of malformed offspring.
Toxicity manifestation (hypervitaminosis A)
The symptoms of hypervitaminosis A include nausea, vomiting, diarrhoea, loss of hair (alopecia), scaly and rough skin, bone and joint pain, enlargement of liver, loss of weight, etc. In pregnant women, the hypervitaminosis A may cause congenital malformation in growing foetus (teratogenic effect). The excess intake of carotenoids is not toxic like vitamin A.
VITAMIN D
Vitamin D is also known as calciferol because of its role in calcium metabolism and anti-rachitic factor because it prevents rickets.
Chemistry
Vitamin D is a steroid compound. There are two forms of vitamin D.
1. The naturally produced D3 or cholecalciferol, is the form obtained from animal sources in the diet, or made in the skin by the action of ultraviolet light from sunlight on 7-dehydrocholesterol.
2. Artificially produced form D2 or ergocalciferol, is the form made in the laboratory by irradiating the plant sterol, ergosterol.
Sources
Best sources are cod liver oil and often fish oils and sunlight induced synthesis of vitamin D3 in skin. Egg yolk and liver are good sources. The table below summarises the sources of food that are rich in vitamin D.
Functions
Vitamin D (Calcitriol) plays an essential role as a hormone in the regulation of calcium and phosphorus metabolism. It maintains the normal plasma level of calcium and phosphorus by acting on intestine, kidneys and bones.
The daily requirements of vitamin D is 200-400IU.
Deficiency manifestations
Rickets: Rickets is characterized by formation of soft and pliable bones due to poor mineralization and calcium deficiency. Due to softness, the weight bearing bones are bent and deformed. The main features of the rickets are, a large head with protruding forehead, pigeon chest, bow legs, (curved legs), knock knees and abnormal curvature of the spine (kyphosis). Rachitic children are usually anaemic or prone to infections. Rickets can be fatal when severe. Rickets is characterized by low plasma levels of calcium and phosphorus and high alkaline phosphatase activity.
Osteomalacias (adult rickets): The deficiency of vitamin D in adults causes osteomalacia. This is a condition similar to that of rickets. Osteomalacia characterized by demineralization of previously formed bones, Demineralization of bones makes them soft and susceptible to fractures.
Vitamin D toxicity (hypervitaminosis D)
High doses of vitamin D over a long period are toxic. The early symptoms of hypervitaminosis D include nausea, vomiting, anorexia, increased thirst, loss of weight, etc. Hypercalcemia is seen due to increased bone resorption and intestinal absorption of calcium. The prolonged hypercalcemia causes calcification of soft tissues and organs such as kidney and may lead to formation of stones in the kidneys.
Vitamin E
Chemistry
Vitamin E consists of eight naturally occurring tocopherols that includes alpha-tocopherol, beta-tocopherol, delta-tocopherol and gamma-tocopherol, of which α-tocopherol is the most active form.
Sources
The major dietary sources of vitamin E are fats and oils. The richest sources are germ oil, corn oil, fish oil, eggs, lettuce and alfalfa. The table below summarize the food that contains high amount of vitamin E.
The daily recommended consumption for vitamin E is about 10 mg (15 IU) of α-tocopherol for a man and 8 mg (12 IU) for a woman.
Functions
Vitamin E acts as a natural antioxidant by scavenging free radicals and molecular oxygen. Vitamin E is also important for preventing peroxidation of polyunsaturated fatty acids in cell membranes. Other than that, protection of erythrocyte membrane from oxidant is the major role of vitamin E in humans by protecting the red blood cell (RBCs) from haemolysis. Vitamin E also helps to prevent oxidation of LDL. Oxidized LDL may be more atherogenic than native LDL and thus vitamin E may protect against atheromatous coronary heart disease.
Deficiency manifestations
Vitamin E deficiency in humans is rare. The major symptom of vitamin E deficiency in human is hemolytic anemia due to an increased red blood cell fragility. Another symptom of vitamin E deficiency is retrolental fibroplasia (RLF) observed in some premature infants of low birth weight. Children with this defect show neuropathy.Toxicity vitamin E (hypervitaminosis E)
Unlike other fat-soluble vitamins such as A and D, vitamin E does not seem to have toxic effects.Vitamin K
Chemistry
This vitamin is called an anti-haemorrhagic factor as its deficiency produced uncontrolled haemorrhages due to defect in blood coagulation. There are two naturally occurring forms of vitamin K that includes Vitamin K1 or phylloquinone derived from plant and vitamin K2 or menaquinones, produced by microorganisms. Both these natural types have the same general activity. Vitamin K3 or menadione is a synthetic product, which is an alkylated form of vitamin K2.
Sources
Excellent sources are cabbage, cauliflower, spinach and other green vegetables. Good sources include tomatoes, cheese, dairy products, meat, egg yolk, etc. The vitamin is also synthesized by microorganisms in the intestinal tract. The table below summarise the foods that contain rich amount of vitamin K.
The suggested intake for adults is 70–140 μg/day.
Functions
Vitamin K plays an important role in blood coagulation. Vitamin K is required for the activation of blood clotting factors, prothrombin (II), factor VII, IX and X. These blood clotting proteins are synthesized in liver in inactive form, and are converted to active form by vitamin K dependent carboxylation reaction. In this, vitamin K dependent carboxylase enzyme adds the extra carboxy group at χ-carbon of glutamic acid residues of inactive blood clotting factors. Vitamin K is also required for the carboxylation of glutamic acid residues of osteocalcin, a Ca2+ binding protein present in bone.
Deficiency manifestations
Vitamin K deficiency is associated with haemorrhagic disease. In vitamin K deficiency, clotting time of blood is increased. Uncontrolled haemorrhages occur on minor injuries as a result of reduction in prothrombin and other clotting factors. Vitamin K is widely distributed in nature and its production by the intestinal microflora ensures that dietary deficiency does not occur. Vitamin K deficiency, however, is found in:
Patients with liver disease and biliary obstruction. Biliary obstruction inhibits the entry of bile salts to the intestine.
In newborn infants, because the placenta does not pass the vitamin to the fetus efficiently, and the gut is sterile immediately after birth.
Following antibiotic therapy that sterilizes the gut.
In fat malabsorption, that impairs absorption of vitamin K.
Toxicity of vitamin K (hypervitaminosis K)
Excessive doses of vitamin K produce a haemolytic anaemia (due to increased breakdown of RBCs) and jaundice (in infants).
Topic 13: Generation of Biochemical Energy
TLO: Describe the importance of ATP as a source of energy.
Adenosine triphosphate (ATP) is a macromolecule made of adenine, ribose and three phosphate group.
Figure 1 Structure of adenosine triphosphate (ATP). [Source: LibreTexts Chemistry]
The structural feature important in ATP is the phosphoric acid anhydride or pyrophosphate linkage. In the hydrolysis reaction, the pyrophosphate bond is hydrolysed when ATP is converted to adenosine diphosphate (ADP) that cause release of energy. Another reason for releasing energy is because hydrolysis process relieves the electron-electron repulsions experienced by the negatively charged phosphate group when they are bonded together.
Figure 2 ATP cycle and reaction coupling [Source: Khan Academy]
If hydrolysis of ATP releases energy, synthesis of ATP requires energy. Check out the hydrolysis and synthesis process of ATP down here:
Figure 3 Hydrolysis and synthesis of ATP.
Organisms use three mechanisms of phosphorylation to generate ATP:
1. Substrate-level phosphorylation generates ATP by transferring a high-energy phosphate group from an intermediate phosphorylated metabolic compound—a substrate—directly to ADP (Tortora & Derrickson, 2017). In human cells, this process occurs in the cytosol during glycolysis and Krebs cycle (refer to Figure 4). The substrate-level phosphorylation takes place both in the presence and absence of oxygen during glycolysis. However, in the Krebs cycle, it happens strictly in an aerobic environment.
Figure 4 The difference between substrate-level phosphorylation and oxidative phosphorylation. [Source: respirationresource.weebly.com]
2. Oxidative phosphorylation removes electrons from organic compounds and passes them through a series of electron acceptors, called the electron transport chain, to molecules of oxygen (O2) (Figure 4). This process occurs in the inner mitochondrial membrane of cells (Tortora & Derrickson, 2017). Checkout the cool process of electron transfer throughout the inner membrane of a mitochondrion!
Figure 5 Electron transport chain [Source: faculty.ccbmd.edu]
3. Photophosphorylation occurs only in chlorophyll-containing plant cells or in certain bacteria that contain other light-absorbing pigments.
Learn more about ATP by clicking this video below:
Topic 14: Acids and Bases
TLO: Compare the role of buffers, exhalation of carbon dioxide, and kidney excretion of H+ in maintaining pH of body fluids
To achieve acid-base balance, there must be a balance between the intake or production of hydrogen ions and net removal of hydrogen ions from the body. The various mechanisms that contribute to the regulation of hydrogen ion concentration are discussed in this chapter.
ACIDS, BASES AND BUFFERS
An acid is defined as a substance that releases protons or hydrogen ions (H+), e.g. hydrochloric acid (HCI), carbonic acid (H2CO3). While a base is a substance that accepts protons or hydrogen ions, e.g. bicarbonate ion (HCO3 –), and HPO42- Proteins in the body also function as bases, because some of the amino acids accept hydrogen ions, e.g. haemoglobin in red blood cells and plasma protein especially albumin is the most important of the body’s bases.
Buffer is a solution of weak acid and the salt of that acid (which functions as weak base) which resists a change in pH when a small amount of acid or base is added to it. By buffering mechanism, a strong acid (or base) is replaced by a weaker one.
NORMAL pH OF THE BODY FLUIDS
The normal pH of arterial blood is 7.4, whereas the pH of venous blood and interstitial fluids is about 7.35 because of the extra amounts of carbon dioxide (CO2), released from the tissues to form H2CO3 in these fluids. Thus, the pH of blood is maintained within a remarkable constant level of 7.35–7.45.
The maintenance of a constant pH is important because, the activities of almost all enzyme systems in the body are influenced by hydrogen ion concentration. Therefore, changes in hydrogen ion concentration alter virtually all cell and body functions, the conformation of biological structural components and uptake and release of oxygen.
REGULATION OF BLOOD pH
To maintain the blood pH at 7.35 –7.45, there are three primary systems that regulate the hydrogen ion concentration in the body fluids. These are:
- Buffer mechanism: First line of defence.
- The respiratory mechanism: Second line of defence.
- Renal mechanism: Third line of defence.
The first two lines of defence keep the hydrogen ion concentration from changing too much until the more slowly responding third line of defence, the kidneys, can eliminate the excess acid or base from the body.
Buffer systems and their role in acid-base balance
The buffer systems of the blood, tissue fluids and cells; immediately combine with acid or base to prevent excessive changes in hydrogen ion concentration. Buffer systems do not eliminate hydrogen ions from the body or add them to the body but only keep them tied up until balance can be re-established.
Various buffer systems are present within the body as stated in the diagram below:
The buffer systems can also be classified according to the location; either extracellularly or intracellularly. The systems are mentioned in the table below:
- The bicarbonate buffer system (HCO3-/ H2CO3)
The bicarbonate buffer system is the most important extracellular buffer. The mechanism of action for the bicarbonate buffer system includes:
When a strong acid, such as HCI, is added to the bicarbonate buffer solution, the increased hydrogen ions are buffered by HCO3–.
This step is formulated as so; HCO3- + H+ à H2CO3.
Thus, hydrogen ions from strong acid (HCI) react with HCO3 to form very weak acid H2CO3.
The opposite reactions take place when a strong base such as sodium hydroxide (NaOH), is added to the bicarbonate buffer solution.
This step is formulated likewise; NaOH +H2CO3 à NaHCO3 +H2O.
In this case, the hydroxyl ion (OH–) from NaOH combines with H2CO3 to form weak base HCO3–. Thus, strong base NaOH is replaced by a weak base NaHCO3.
2. The phosphate buffer system (HPO42- / H2PO4-)
The phosphate buffer system is not important as a blood buffer, it plays a major role in buffering renal tubular fluid and intracellular fluids. Its concentration in both plasma and erythrocytes is low, i.e. only 8% of the concentration of the bicarbonate buffer. Therefore, the total buffering power of the phosphate system in the blood is much less than that of the bicarbonate buffering system.
The mechanism of action for phosphate buffer are:
When a strong acid like HCl is added to the phosphate buffer system, the H+ is accepted by the base HPO42- and converted to H2PO4- which then minimize the pH reduction. The step is formulated likewise;
HCl + Na2HPO4 à H2PO4- + NaCl
When a strong base like NaOH is added to the phosphate buffer system, the OH- is buffered by the H2PO4- to form HPO42- and water. Thus, strong base NaOH is replaced by weak base HPO42- leading to increase of pH. The step is formulated as so;
NaOH + NaH2PO4- à Na2HPO4 +H2O
3. Protein buffer
i. Plasma protein buffer: In the blood, plasma proteins especially albumin act as buffer because proteins contain a large number of dissociable acidic (COOH) and basic (NH2) groups in their structure. In acid solution they act as a buffer in that, the basic amino group (NH2) takes up excess H+ ions forming (NH3+). Whereas in basic solutions the acidic COOH groups give up hydrogen ion forming OH– of alkali to water.
ii. Haemoglobin buffer: Haemoglobin is the major intracellular buffer of blood which is present in erythrocytes. It buffers carbonic acid (H2CO3) and its anhydride CO2 from the tissues.
Exam
- Opened: Monday, 25 September 2023, 5:12 PMClosed: Wednesday, 27 September 2023, 5:12 PM