NEET MDS Lessons
Biochemistry
PHOSPHORUS
Serum level of phosphate is 3-4 mg/dl for adults and 5-6 mg/dl in children. Consumption of calcitriol increases phosphate absorption.
Functions of phosphorus
(a) Plays key role in formation of tooth and bone
(b) Production of high energy phosphate compounds such as ATP, CTP, GTP etc.,
(c) Synthesis of nucleotide co-enzymes such as NAD and NADP
(d) Formation of phosphodiester backbone structure for DNA and RNA synthesis
Hypophosphatemia is the condition which leads to decrease in absorption of phosphorus. it leads to hypercalcamia
Hyperphosphatemia, increase in absorption of phosphate was noticed. Hyperphosphatemia leads to cell lysis, hypocalcemia and thyrotoxicosis.
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
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.
Polyprotic Acids
• Some acids are polyprotic acids; they can lose more than one proton.
• In this case, the conjugate base is also a weak acid.
• For example: Carbonic acid (H2CO3 ) can lose two protons sequentially.
• Each dissociation has a unique Ka and pKa value.
Ka1 = [H+ ][HCO3 - ] / [H2CO3]
Ka2 = [H+ ][CO3 -2 ] / [HCO3- ]
Note: (The difference between a weak acid and its conjugate base differ is one hydrogen)
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.
Glycogenolysis
Breakdown of glycogen to glucose is called glycogenolysis. The Breakdown of glycogen takes place in liver and muscle. In Liver , the end product of glycodgen breakdown is glucose where as in muscles the end product is Lactic acid Under the combined action of Phosphorylase (breaks only –α-(1,4) linkage )and Debranching enzymes (breaks only α-(1,6) linkage )glycogen is broken down to glucose.
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.