NEET MDS Lessons
Biochemistry
Erythrocytes and the Pentose Phosphate Pathway
The predominant pathways of carbohydrate metabolism in the red blood cell (RBC) are glycolysis, the PPP and 2,3-bisphosphoglycerate (2,3-BPG) metabolism (refer to discussion of hemoglobin for review of the synthesis and role role of 2,3-BPG).
Glycolysis provides ATP for membrane ion pumps and NADH for re-oxidation of methemoglobin. The PPP supplies the RBC with NADPH to maintain the reduced state of glutathione.
The inability to maintain reduced glutathione in RBCs leads to increased accumulation of peroxides, predominantly H2O2, that in turn results in a weakening of the cell wall and concomitant hemolysis.
Accumulation of H2O2 also leads to increased rates of oxidation of hemoglobin to methemoglobin that also weakens the cell wall.
Glutathione removes peroxides via the action of glutathione peroxidase.
The PPP in erythrocytes is essentially the only pathway for these cells to produce NADPH.
Any defect in the production of NADPH could, therefore, have profound effects on erythrocyte survival.
Vitamin B6: Pyridoxine, Pyridoxal, Pyridoxamine
Aids in protein metabolism and red blood cell formation. It is also involved in the body’s production of chemicals such as insulin and hemoglobin.
Vitamin B6 Deficiency Deficiency symptoms include skin disorders, dermatitis, cracks at corners of mouth, anemia, kidney stones, and nausea. A vitamin B6 deficiency in infants can cause mental confusion.
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.
VITAMIN C: ASCORBIC ACID, ASCORBATE
Vitamin C benefits the body by holding cells together through collagen synthesis; collagen is a connective tissue that holds muscles, bones, and other tissues together. Vitamin C also aids in wound healing, bone and tooth formation, strengthening blood vessel walls, improving immune system function, increasing absorption and utilization of iron, and acting as an antioxidant.
RDA The Recommended Dietary Allowance (RDA) for Vitamin C is 90 mg/day for adult males and 75 mg/day for adult females
Vitamin C Deficiency
Severe vitamin C deficiency result in the disease known as scurvy, causing a loss of collagen strength throughout the body. Loss of collagen results in loose teeth, bleeding and swollen gums, and improper wound healing.
VITAMINS
Based on solubility Vitamins are classified as either fat-soluble (lipid soluble) or water-soluble. Vitamins A, D, E and K are fat-soluble
Vitamin C and B is water soluble.
B-COMPLEX VITAMINS
Eight of the water-soluble vitamins are known as the vitamin B-complex group: thiamin (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), vitamin B6 (pyridoxine), folate (folic acid), vitamin B12, biotin and pantothenic acid.
Buffers
• Biological systems use buffers to maintain pH.
• Definition: A buffer is a solution that resists a significant change in pH upon addition of an acid or a base.
• Chemically: A buffer is a mixture of a weak acid and its conjugate base
• Example: Bicarbonate buffer is a mixture of carbonic acid (the weak acid) and the bicarbonate ion (the conjugate base): H2CO3 + HCO3 –
• All OH- or H+ ions added to a buffer are consumed and the overall [H+ ] or pH is not altered
H2CO3 + HCO3 - + H+ <- -> 2H2CO3
H2CO3 + HCO3 - + OH- <- -> 2HCO3 - + H2O
• For any weak acid / conjugate base pair, the buffering range is its pKa +1.
It should be noted that around the pKa the pH of a solution does not change appreciably even when large amounts of acid or base are added. This phenomenon is known as buffering. In most biochemical studies it is important to perform experiments, that will consume H+ or OH- equivalents, in a solution of a buffering agent that has a pKa near the pH optimum for the experiment.
Most biologic fluids are buffered near neutrality. A buffer resist a pH change and consists of a conjugate acid/base pair.
Important Physiological Buffers include carbonate (H2CO3/HCO3-),
Phosphate (H2PO-4 /HPO2-4) and various protiens
Role of Coenzymes
The functional role of coenzymes is to act as transporters of chemical groups from one reactant to another.
Ex. The hydride ion (H+ + 2e-) carried by NAD or the mole of hydrogen carried by FAD;
The amine (-NH2) carried by pyridoxal phosphate