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.
Anaerobic organisms lack a respiratory chain. They must reoxidize NADH produced in Glycolysis through some other reaction, because NAD+ is needed for the Glyceraldehyde-3-phosphate Dehydrogenase reaction (see above). Usually NADH is reoxidized as pyruvate is converted to a more reduced compound, that may be excreted.
The complete pathway, including Glycolysis and the re-oxidation of NADH, is called fermentation.
For example, Lactate Dehydrogenase catalyzes reduction of the keto group in pyruvate to a hydroxyl, yielding lactate, as NADH is oxidized to NAD+.
Skeletal muscles ferment glucose to lactate during exercise, when aerobic metabolism cannot keep up with energy needs. Lactate released to the blood may be taken up by other tissues, or by muscle after exercise, and converted via the reversible Lactate Dehydrogenase back to pyruvate
Fermentation Pathway, from glucose to lactate (omitting H+):
glucose + 2 ADP + 2 Pi → 2 lactate + 2 ATP
Anaerobic catabolism of glucose yields only 2 “high energy” bonds of ATP.
Thiamin: Vitamin B1
Thiamin, or vitamin B1, helps to release energy from foods, promotes normal appetite, and is important in maintaining proper nervous system function.
RDA (Required Daily allowance) Males: 1.2 mg/day; Females: 1.1 mg/day
Thiamin Deficiency
Symptoms of thiamin deficiency include: mental confusion, muscle weakness, wasting, water retention (edema), impaired growth, and the disease known as beriberi.
Factors regulating blood calcium level
(i) Vitamin D
(a) Vitamin D and absorption of calcium: Active form of calcium is calcitriol. Calcitriol enters intestinal wall and binds to cytoplasmic receptor and then binds with DNA causes depression and consequent transcription of gene code for calbindin. Due to increased availability of calbindin, absorption of calcium increases leading to increased blood calcium level.
(b) Vitamin D and Bone: Vitamin D activates osteoblast, bone forming cells & also stimulates secretion of alkaline phosphatase. Due to this enzyme, calcium and phosphorus increase.
(c) Vitamin D and Kidney: Calcitriol increase reabsorption of calcium and phosphorus by renal tubules.
(ii) Parathyroid hormone (PTH)
Normal PTH level in serum is 10-60ng/l.
(a) PTH and bones: In bone, PTH causes demineralization. It also causes recreation of collagenase from osteoclast leads to loss of matrix and bone resorption. As a result, mucopolysacharides and hydroxyproline are excreted in urine.
(b) PTH and Kidney: In kidney, PTH causes increased reabsorption of calcium but decreases reabsorption of phosphorus from kidney tubules.
(iii) Calcitonin Calcitonin decreases serum calcium level. It inhibits resorption of bone. It decreases the activity of osteoclasts and increases osteoblasts.
Hyper Calcemia When plasma Ca2+ level is more than 11mg/dl is called Hypercalcemia. It is due to parathyroid adenoma or ectopic PTH secreting tumor. calcium excreted in urine decreases excretion of chloride causing hyperchloremic acidosis.
Hypocalcemia Plasma calcium level less than 8mg/dl is called hypocalcemia. Tetany due to accidental surgical removal of parathyroid glands or by autoimmune disease. In tetany, neuromuscular irritability is increased. Increased Q-7 internal in ECG is seen. Main manifestation is carpopedal spasm. Laryngismus and stridor are also observed.
Titration of a weak acid with a strong base
• A weak acid is mostly in its conjugate acid form
• When strong base is added, it removes protons from the solution, more and more acid is in the conjugate base form, and the pH increases
• When the moles of base added equals half the total moles of acid, the weak acid and its conjugate base are in equal amounts. The ratio of CB / WA = 1 and according to the HH equation, pH = pKa + log(1) or pH = pKa.
• If more base is added, the conjugate base form becomes greater till the equivalance point when all of the acid is in the conjugate base form.
The basic characteristics of enzymes includes
(i) Almost all the enzymes are proteins and they follow the physical and chemical reactions of proteins (ii) Enzymes are sensitive and labile to heat
(iii) Enzymes are water soluble
(iv) Enzymes could be precipitated by protein precipitating agents such as ammonium sulfate and trichloroacetic acid.
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.