NEET MDS Lessons
Biochemistry
CLINICAL SIGNIFICANCE OF ENZYMES
The measurement of enzymes level in serum is applied in diagnostic application
Pancreatic Enzymes
Acute pancreatitis is an inflammatory process where auto digestion of gland was noticed with activation of the certain pancreatic enzymes. Enzymes which involves in pancreatic destruction includes α-amylase, lipase etc.,
1. α-amylase (AMYs) are calcium dependent hydrolyase class of metaloenzyme that catalyzes the hydrolysis of 1, 4- α-glycosidic linkages in polysaccharides. The normal values of amylase is in range of 28-100 U/L. Marked increase of 5 to 10 times the upper reference limit (URL) in AMYs activity indicates acute pancreatitis and severe glomerular impairment.
2. Lipase is single chain glycoprotein. Bile salts and a cofactor called colipase are required for full catalytic activity of lipase. Colipase is secreted by pancreas. Increase in plasma lipase activity indicates acute pancreatitis and carcinoma of the pancreas.
Liver Enzymes
Markers of Hepatocellular Damage
1. Aspartate transaminase (AST) Aspartate transaminase is present in high concentrations in cells of cardiac and skeletal muscle, liver, kidney and erythrocytes. Damage to any of these tissues may increase plasma AST levels.
The normal value of AST for male is <35 U/ L and for female it is <31 U/L.
2. Alanine transaminase (ALT) Alanine transaminase is present at high concentrations in liver and to a lesser extent, in skeletal muscle, kidney and heart. Thus in case of liver damage increase in both AST and ALT were noticed. While in myocardial infarction AST is increased with little or no increase in ALT.
The normal value of ALT is <45 U/L and <34 U/L for male and female respectively
Markers of cholestasis
1. Alkaline phosphatases
Alkaline phosphatases are a group of enzymes that hydrolyse organic phosphates at high pH. They are present in osteoblasts of bone, the cells of the hepatobiliary tract, intestinal wall, renal tubules and placenta.
Gamma-glutamyl-transferase (GGT) Gamma-glutamyl-transferase catalyzes the transfere of the γ–glutamyl group from peptides. The activity of GGT is higher in men than in women. In male the normal value of GGT activity is <55 U/L and for female it is <38 U/L.
2. Glutamate dehydrogenase (GLD) Glutamate dehydrogenase is a mitochondrial enzyme found in liver, heart muscle and kidneys.
Muscle Enzymes
1. Creatine Kinase Creatine kinase (CK) is most abundant in cells of brain, cardiac and skeletal.
2. Lactate Dehydrogenase
Lactate dehydrogenase (LD) catalyses the reversible interconversion of lactate and pyruvate.
LIPOPROTIENS
Lipoproteins Consist of a Nonpolar Core & a Single Surface Layer of Amphipathic Lipids
The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules .These are oriented so that their polar groups face outward to the aqueous medium. The protein moiety of a lipoprotein is known as an apolipoprotein or apoprotein,constituting nearly 70% of some HDL and as little as 1% of Chylomicons. Some apolipoproteins are integral and cannot be removed, whereas others can be freely transferred to other lipoproteins.
There re five types of lipoproteins, namely chylomicrons, very low density lipoproteins(VLDL) low density lipoproteins (LDL), high density Lipoproteins (HDL) and free fatty acid-albumin complexes.
Function of Calcium
The major functions of calcium are
(a) Excitation and contraction of muscle fibres needs calcium. The active transport system utilizing calcium binding protein is called Calsequestrin. Calcium decreases neuromuscular irritability.
(b) Calcium is necessary for transmission of nerve impulse from presynaptic to postsynaptic region.
(c) Calcium is used as second messenger in system involving protein and inositol triphosphate.
(d) Secretion of insulin, parathyroid hormone, calcium etc, from the cells requires calcium.
(e) Calcium decrease the passage of serum through capillaries thus, calcium is clinically used to reduce allergic exudates.
(f) Calcium is also required for coagulation factors such as prothrombin.
(g) Calcium prolongs systole.
(h) Bone and teeth contains bulk quantity of calcium.
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b Oxidation Pathway |
Fatty Acid Synthesis |
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pathway location |
mitochondrial matrix |
cytosol |
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acyl carriers (thiols) |
Coenzyme-A |
phosphopantetheine (ACP) & cysteine |
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electron acceptors/donor |
FAD & NAD+ |
NADPH |
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hydroxyl intermediate |
L |
D |
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2-C product/donor |
acetyl-CoA |
malonyl-CoA (& acetyl-CoA) |
SELENIUM
normal serum level is 50-100 mg/day
Selenium dependent enzymes include glutathione Peroxidase and 5-de-iodinase. Selenium concentration in testis is the highest in adult. It is very necessary for normal development and maturation of sperm.
Sugar derivatives
Sugar alcohol - lacks an aldehyde or ketone. An example is ribitol.
Sugar acid - the aldehyde at C1, or the hydroxyl on the terminal carbon, is oxidized to a carboxylic acid. Examples are gluconic acid and glucuronic acid
Amino sugar - an amino group substitutes for one of the hydroxyls. An example is glucosamine. The amino group may be acetylated.
N-acetylneuraminate, (N-acetylneuraminic acid, also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Sialic acid imparts negative charge to glycoproteins, because its carboxyl group tends to dissociate a proton at physiological pH.
Glycosidic bonds: The anomeric hydroxyl group and a hydroxyl group of another sugar or some other compound can join together, splitting out water to form a glycosidic bond.
R-OH + HO-R' → R-O-R' + H2O
Disaccharides: Maltose, a cleavage product of starch, is a disaccharide with an α (1→4) glycosidic linkage between the C1 hydroxyl of one glucose and the C4 hydroxyl of a second glucose. Maltose is the α anomer, because the O at C1 points down from the ring.
Cellobiose, a product of cellulose breakdown, is the otherwise equivalent β anomer. The configuration at the anomeric C1 is β (O points up from the ring). The β(1→4) glycosidic linkage is represented as a "zig-zag" line, but one glucose residue is actually flipped over relative to the other.
Other disaccharides
- Sucrose, common table sugar, has a glycosidic bond linking the anomeric hydroxyls of glucose and fructose. Because the configuration at the anomeric carbon of glucose is α (O points down from the ring), the linkage is designated α (1→2). The full name is α -D-glucopyranosyl-(1→2) β -D- fructopyranose.
- Lactose, milk sugar, is composed of glucose and galactose with β (→4) linkage → the anomeric hydroxyl of galactose. Its full name is β -D-galactopyranosyl-(1→)- α -D-glucopyranose
Polysaccharides:
Plants store glucose as amylose or amylopectin, glucose polymers collectively called starch. Glucose storage in polymeric form minimizes osmotic effects
Amylose is a glucose polymer with α (1→4) glycosidic linkages, as represented above. The end of the polysaccharide with an anomeric carbon (C1) that is not involved in a glycosidic bond is called the reducing end
Amylopectin is a glucose polymer with mainly α (1→4) linkages, but it also has branches formed by α (1→6) linkages. The branches are generally longer than shown above. The branches produce a compact structure, and provide multiple chain ends at which enzymatic cleavage of the polymer can occur.
Glycogen, the glucose storage polymer in animals, is similar in structure to amylopectin. But glycogen has more α (1→6) branches. The highly branched structure permits rapid release of glucose from glycogen stores, e.g., in muscle cells during exercise. The ability to rapidly mobilize glucose is more essential to animals than to plants.
Cellulose, a major constituent of plant cell walls, consists of long linear chains of glucose, with β (1→4) linkages. Every other glucose in cellulose is flipped over, due to the β linkages. This promotes intrachain and interchain hydrogen bonds, as well as van der Waals interactions, that cause cellulose chains to be straight and rigid, and pack with a crystalline arrangement in thick bundles called microfibrils.
Glycosaminoglycans (mucopolysaccharides) are polymers of repeating disaccharides. Within the disaccharides, the sugars tend to be modified, with acidic groups, amino groups, sulfated hydroxyl and amino groups, etc. Glycosaminoglycans tend to be negatively charged, because of the prevalence of acidic groups.
Hyaluronate is a glycosaminoglycan with a repeating disaccharide consisting of two glucose derivatives, glucuronate (glucuronic acid) and N-acetylglucosamine. The glycosidic linkages are β(1→3) and β(1→4).
When covalently linked to specific core proteins, glycosaminoglycans form complexes called proteoglycans. Some proteoglycans of the extracellular matrix in turn link non-covalently to hyaluronate via protein domains called link modules. For example, in cartilage multiple copies of the aggrecan proteoglycan bind to an extended hyaluronate backbone to form a large complex Versican, another proteoglycan that binds to hyaluronate, is in the extracellular matrix of loose connective tissues.
Heparan sulfate is initially synthesized on a membrane-embedded core protein as a polymer of alternating glucuronate and N-acetylglucosamine residues. Later, in segments of the polymer, glucuronate residues may be converted to a sulfated sugar called iduronic acid, while N-acetylglucosamine residues may be deacetylated and/or sulfated
Heparin, a glycosaminoglycan found in granules of mast cells, has a structure similar to that of heparan sulfates, but is relatively highly sulfated.
Some cell surface heparan sulfate glycosaminoglycans remain covalently linked to core proteins embedded in the plasma membrane. Proteins involved in signaling and adhesion at the cell surface have been identified that recognize and bind segments of heparan sulfate chains having particular patterns of sulfation
Lectins are glycoproteins that recognize and bind to specific oligosaccharides.
- Concanavalin A and wheat germ agglutinin are plant lectins that have been useful research tools
- Mannan-binding lectin (MBL) is a glycoprotein found in blood plasma. It associates with cell surface carbohydrates of disease-causing microorganisms, promoting phagocytosis of these organisms as part of the immune response.
- Selectins are integral proteins of the plasma membrane with lectin-like domains that protrude on the outer surface of mammalian cells. Selectins participate in cell-cell recognition and binding.
FAT-SOLUBLE VITAMINS
The fat-soluble vitamins, A, D, E, and K, are stored in the body for long periods of time and generally pose a greater risk for toxicity when consumed in excess than water-soluble vitamins.
VITAMIN A: RETINOL
Vitamin A, also called retinol, has many functions in the body. In addition to helping the eyes adjust to light changes, vitamin A plays an important role in bone growth, tooth development, reproduction, cell division, gene expression, and regulation of the immune system.
The skin, eyes, and mucous membranes of the mouth, nose, throat and lungs depend on vitamin A to remain moist. Vitamin A is also an important antioxidant that may play a role in the prevention of certain cancers.
One RAE equals 1 mcg of retinol or 12 mcg of beta-carotene. The Recommended Dietary Allowance (RDA) for vitamin A is 900 mcg/ day for adult males and 700 mcg/ day for adult females.
Vitamin A Deficiency
Vitamin A deficiency is rare, but the disease that results is known as xerophthalmia.
Other signs of possible vitamin A deficiency include decreased resistance to infections, faulty tooth development, and slower bone growth.
Vitamin A toxicity The Tolerable Upper Intake Level (UL) for adults is 3,000 mcg RAE.
VITAMIN D
Vitamin D plays a critical role in the body’s use of calcium and phosphorous. It works by increasing the amount of calcium absorbed from the small intestine, helping to form and maintain bones.
Vitamin D benefits the body by playing a role in immunity and controlling cell growth. Children especially need adequate amounts of vitamin D to develop strong bones and healthy teeth.
RDA From 12 months to age fifty, the RDA is set at 15 mcg.
20 mcg of cholecalciferol equals 800 International Units (IU), which is the recommendation for maintenance of healthy bone for adults over fifty.
Vitamin D Deficiency
Symptoms of vitamin D deficiency in growing children include rickets (long, soft bowed legs) and flattening of the back of the skull. Vitamin D deficiency in adults may result in osteomalacia (muscle and bone weakness), and osteoporosis (loss of bone mass).
Vitamin D toxicity
The Tolerable Upper Intake Level (UL) for vitamin D is set at 100 mcg for people 9 years of age and older. High doses of vitamin D supplements coupled with large amounts of fortified foods may cause accumulations in the liver and produce signs of poisoning.
VITAMIN E: TOCOPHEROL
Vitamin E benefits the body by acting as an antioxidant, and protecting vitamins A and C, red blood cells, and essential fatty acids from destruction.
RDA One milligram of alpha-tocopherol equals to 1.5 International Units (IU). RDA guidelines state that males and females over the age of 14 should receive 15 mcg of alpha-tocopherol per day.
Vitamin E Deficiency Vitamin E deficiency is rare. Cases of vitamin E deficiency usually only occur in premature infants and in those unable to absorb fats.
VITAMIN K
Vitamin K is naturally produced by the bacteria in the intestines, and plays an essential role in normal blood clotting, promoting bone health, and helping to produce proteins for blood, bones, and kidneys.
RDA
Males and females age 14 - 18: 75 mcg/day; Males and females age 19 and older: 90 mcg/day
Vitamin K Deficiency
Hemorrhage can occur due to sufficient amounts of vitamin K.
Vitamin K deficiency may appear in infants or in people who take anticoagulants, such as Coumadin (warfarin), or antibiotic drugs.
Newborn babies lack the intestinal bacteria to produce vitamin K and need a supplement for the first week.