NEET MDS Lessons
Biochemistry
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
ISO-ENZYMES
Iso-enzymes are physically distinct forms of the same enzyme activity. Higher organisms have several physically distinct versions of a given enzyme, each of which catalyzes the same reaction. Isozymes arise through gene duplication and exhibit differences in properties such as sensitivity to particular regulatory factors or substrate affinity that adapts them to specific tissues or circumstances.
Isoforms of Lactate dehydrogenase is useful in diagnosis of myocardial infarction. While study of alkaline phosphatase isoforms are helpful in diagnosis of various bone disorder and obstructive liver diseases.
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.
Clinical significance
Primary hyperparathyroidism is due to autonomous, abnormal hypersecretion of PTH in the parathyroid gland
Secondary hyperparathyroidism is an appropriately high PTH level seen as a physiological response to hypocalcemia.
A low level of PTH in the blood is known as hypoparathyroidism and is most commonly due to damage to or removal of parathyroid glands during thyroid surgery.
CLASSIFICATION OF LIPIDS
Lipids are classified as follows:
1. Simple lipids: Esters of fatty acids with various alcohols.
(a) Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state. A long-chain carboxylic acid; those in animal fats and vegetable oils often have 12–22 carbon atoms.
(b) Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols. Waxes are carboxylic acid esters, RCOOR’ ,with long, straight hydrocarbon chains in both R groups
2. Complex lipids: Esters of fatty acids containing groups in addition to an alcohol and a fatty acid.
(a) Phospholipids: Lipids containing, in addition to fatty acids and an alcohol, a phosphoric acid residue. They frequently have nitrogen containing bases and other substituents,
Eg glycerophospholipids the alcohol is glycerol
sphingophospholipids the alcohol is sphingosine.
(b) Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine, and carbohydrate. These lipids contain a fatty acid, carbohydrate and nitrogenous base. The alcohol is sphingosine, hence they are also called as glycosphingolipids. Clycerol and phosphate are absent
e.g., cerebrosides, gangliosides.
(c) Other complex lipids: Lipids such as sulfolipids and aminolipids. Lipoproteins may also be placed in this category.
3. Precursor and derived lipids: These include fatty acids, glycerol, steroids, other alcohols, fatty aldehydes, and ketone bodies, hydrocarbons, lipid soluble vitamins, and hormones. Because they are uncharged, acylglycerols (glycerides), cholesterol, and cholesteryl esters are termed neutral lipids
4. Miscellaneous lipids: These include a large number of compounds possessing the characteristics of lipids e.g., carotenoids, squalene, hydrocarbons such as pentacosane (in bees wax), terpenes etc.
NEUTRAL LIPIDS: The lipids which are uncharged are referred to as neutral lipids. These are mono-, di-, and triacylglycerols, cholesterol and cholesteryl esters.
Glycolysis enzymes are located in the cytosol of cells. Pyruvate enters the mitochondrion to be metabolized further
Mitochondrial compartments: The mitochondrial matrix contains Pyruvate Dehydrogenase and enzymes of Krebs Cycle, plus other pathways such as fatty acid oxidation.
Pyruvate Dehydrogenase catalyzes oxidative decarboxylation of pyruvate, to form acetyl-CoA
FAD (Flavin Adenine Dinucleotide) is a derivative of the B-vitamin riboflavin (dimethylisoalloxazine-ribitol). The flavin ring system undergoes oxidation/reduction as shown below. Whereas NAD+ is a coenzyme that reversibly binds to enzymes, FAD is a prosthetic group, that is permanently part of the complex.
FAD accepts and donates 2 electrons with 2 protons (2 H):
Thiamine pyrophosphate (TPP) is a derivative of thiamine (vitamin B1). Nutritional deficiency of thiamine leads to the disease beriberi. Beriberi affects especially the brain, because TPP is required for carbohydrate metabolism, and the brain depends on glucose metabolism for energy
Acetyl CoA, a product of the Pyruvate Dehydrogenase reaction, is a central compound in metabolism. The "high energy" thioester linkage makes it an excellent donor of the acetate moiety
For example, acetyl CoA functions as:
- input to the Krebs Cycle, where the acetate moiety is further degraded to CO2.
- donor of acetate for synthesis of fatty acids, ketone bodies, and cholesterol.
ATPs formed in TCA cycle from one molecule of Pyruvate
1. 3ATP 7. 3ATP 5. 3 ATP
8. 1 ATP 9. 2 ATP 11.3 ATP Total =15 ATP.
ATPS formed from one molecule of Acetyl CoA =12ATP
ATPs formed from one molecule of glucose after complete oxidation
One molecule of glucose -->2 molecules of pyruvate
['By glycolysis] ->8 ATP
2 molecules of pyruvate [By TCA cycle] -> 30 ATP
Total = 38 ATP
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.