NEET MDS Lessons
Biochemistry
Enzymes are protein catalyst produced by a cell and responsible ‘for the high rate’ and specificity of one or more intracellular or extracellular biochemical reactions.
Enzymes are biological catalysts responsible for supporting almost all of the chemical reactions that maintain animal homeostasis. Enzyme reactions are always reversible.
The substance, upon which an enzyme acts, is called as substrate. Enzymes are involved in conversion of substrate into product.
Almost all enzymes are globular proteins consisting either of a single polypeptide or of two or more polypeptides held together (in quaternary structure) by non-covalent bonds. Enzymes do nothing but speed up the rates at which the equilibrium positions of reversible reactions are attained.
In terms of thermodynamics, enzymes reduce the activation energies of reactions, enabling them to occur much more readily at low temperatures - essential for biological systems.
Glycogen Metabolism
The formation of glycogen from glucose is called Glycogenesis
Glycogen is a polymer of glucose residues linked mainly by a(1→ 4) glycosidic linkages. There are a(1→6) linkages at branch points. The chains and branches are longer than shown. Glucose is stored as glycogen predominantly in liver and muscle cells
Glycogen Synthesis
Uridine diphosphate glucose (UDP-glucose) is the immediate precursor for glycogen synthesis. As glucose residues are added to glycogen, UDP-glucose is the substrate and UDP is released as a reaction product. Nucleotide diphosphate sugars are precursors also for synthesis of other complex carbohydrates, including oligosaccharide chains of glycoproteins, etc.
UDP-glucose is formed from glucose-1-phosphate and uridine triphosphate (UTP)
glucose-1-phosphate + UTP → UDP-glucose + 2 Pi
Cleavage of PPi is the only energy cost for glycogen synthesis (1P bond per glucose residue)
Glycogenin initiates glycogen synthesis. Glycogenin is an enzyme that catalyzes glycosylation of one of its own tyrosine residues.
Physiological regulation of glycogen metabolism
Both synthesis and breakdown of glycogen are spontaneous. If glycogen synthesis and phosphorolysis were active simultaneously in a cell, there would be a futile cycle with cleavage of 1 P bond per cycle
To prevent such a futile cycle, Glycogen Synthase and Glycogen Phosphorylase are reciprocally regulated, both by allosteric effectors and by covalent modification (phosphorylation)
Glycogen catabolism (breakdown)
Glycogen Phosphorylase catalyzes phosphorolytic cleavage of the →(1→4) glycosidic linkages of glycogen, releasing glucose-1-phosphate as the reaction product.
Glycogen (n residues) + Pi → glycogen (n-1 residues) + glucose-1-phosphate
The Major product of glycogen breakdown is glucose -1-phosphate
Fate of glucose-1-phosphate in relation to other pathways:
Phosphoglucomutase catalyzes the reversible reaction:
Glucose-1-phosphate → Glucose-6-phosphate
Folate: Folic Acid, Folacin Folate, also known as folic acid or folacin, aids in protein metabolism, promoting red blood cell formation, and lowering the risk for neural tube birth defects. Folate may also play a role in controlling homocysteine levels, thus reducing the risk for coronary heart disease.
RDA for folate is 400 mcg/day for adult males and females. Pregnancy will increase the RDA for folate to 600 mcg/day.
Folate Deficiency
Folate deficiency affects cell growth and protein production, which can lead to overall impaired growth. Deficiency symptoms also include anemia and diarrhea.
A folate deficiency in women who are pregnant or of child bearing age may result in the delivery of a baby with neural tube defects such as spina bifida.
Classification of Fatty Acids and Triglycerides
Short-chain: 2-4 carbon atoms
Medium-chain: 6-12 carbon atoms
Long-chain: 14-20 carbon atoms
Very long-chain: >20 carbon atoms
• are usually in esterified form as major components of other lipids
A16-carbon fatty acid, with one cis double bond between carbon atoms 9 and 10 may be represented as 16:1 cisD9.
Double bonds in fatty acids usually have the cis configuration. Most naturally occurring fatty acids have an even number of carbon atoms
Examples of fatty acids
|
18:0 |
stearic acid |
|
18:1 cisD9 |
oleic acid |
|
18:2 cisD9,12 |
linoleic acid |
|
18:3 cisD9,12,15 |
linonenic acid |
|
20:4 cisD5,8,11,14 |
arachidonic acid |
There is free rotation about C-C bonds in the fatty acid hydrocarbon, except where there is a double bond. Each cis double bond causes a kink in the chain,
Ampholytes, Polyampholytes, pI and Zwitterion
Many substances in nature contain both acidic and basic groups as well as many different types of these groups in the same molecule. (e.g. proteins). These are called ampholytes (one acidic and one basic group) or polyampholytes (many acidic and basic groups). Proteins contains many different amino acids some of which contain ionizable side groups, both acidic and basic. Therefore, a useful term for dealing with the titration of ampholytes and polyampholytes (e.g. proteins) is the isoelectric point, pI. This is described as the pH at which the effective net charge on a molecule is zero.
For the case of a simple ampholyte like the amino acid glycine the pI, when calculated from the Henderson-Hasselbalch equation, is shown to be the average of the pK for the a-COOH group and the pK for the a-NH2 group:
pI = [pKa-(COOH) + pKa-(NH3+)]/2
For more complex molecules such as polyampholytes the pI is the average of the pKa values that represent the boundaries of the zwitterionic form of the molecule. The pI value, like that of pK, is very informative as to the nature of different molecules. A molecule with a low pI would contain a predominance of acidic groups, whereas a high pI indicates predominance of basic groups.
Regulation of PTH secretion
Secretion of parathyroid hormone is controlled chiefly by serum [Ca2+] through negative feedback. Calcium-sensing receptors located on parathyroid cells are activated when [Ca2+] is low.
Hypomagnesemia inhibits PTH secretion and also causes resistance to PTH, leading to a form of hypoparathyroidism that is reversible.
Hypermagnesemia also results in inhibition of PTH secretion.
Stimulators of PTH includes decreased serum [Ca2+], mild decreases in serum [Mg2+], and an increase in serum phosphate.
Inhibitors include increased serum [Ca2+], severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism (such as hypocalcemia), and calcitriol.
COPPER
The normal serum level of copper is 25 to 50 mg/dl.
Functions of copper
(a) Copper is necessary for iron absorption and incorporation of iron into hemoglobin.
(b) It is very essential for tyrosinase activity
(c) It is the co-factor for vitamin C requiring hydroxylation
(d) Copper increases the level of high density lipo protein and protects the heart.
Wilson’s disease
In case of Wilson’s disease ceruloplasmin level in blood is drastically reduced.
Wilson’s disease leads to
(i) Accumulation of copper in liver leads to hepatocellular degeneration and cirrhosis
(ii) Deposition of copper in brain basal ganglia leads to leticular degeneration
(iii) Copper deposits as green pigmented ring around cornea and the condition is called as Kayser-Kleischer ring
Over accumulation of copper can be treated by consumption of diet containg low copper and injection of D-penicillamine, which excretes copper through urine.
Menke’s kidney hair syndrome
It is X-linked defect. In this condition copper is absorbed by GI tract, but cannot be transported to blood. The defect in transport of copper to blood is due to absence of an intracellular copper binding ATPase.