NEET MDS Lessons
Biochemistry
During fasting or carbohydrate starvation, oxaloacetate is depleted in liver because it is used for gluconeogenesis. This impedes entry of acetyl-CoA into Krebs cycle. Acetyl-CoA then is converted in liver mitochondria to ketone bodies, acetoacetate and b-hydroxybutyrate.
Three enzymes are involved in synthesis of ketone bodies:
b-Ketothiolase. The final step of the b-oxidation pathway runs backwards, condensing 2 acetyl-CoA to produce acetoacetyl-CoA, with release of one CoA.
HMG-CoA Synthase catalyzes condensation of a third acetate moiety (from acetyl-CoA) with acetoacetyl-CoA to form hydroxymethylglutaryl-CoA (HMG-CoA).
HMG-CoA Lyase cleaves HMG-CoA to yield acetoacetate plus acetyl-CoA.
b-Hydroxybutyrate Dehydrogenase catalyzes inter-conversion of the ketone bodies acetoacetate and b-hydroxybutyrate.
Ketone bodies are transported in the blood to other tissue cells, where they are converted back to acetyl-CoA for catabolism in Krebs cycle
FACTORS AFFECTING ENZYME ACTIVITY
Velocity or rate of enzymatic reaction is assessed by the rate of change in concentration of substrate or product at a given time duration. Various factors which affect the activity of enzymes include:
1. Substrate concentration
2. Enzyme concentration
3. Product concentration
4. Temperature 5. Hydrogen ion concentration (pH)
6. Presence of activators
7. Presence of inhibitor
Effect of substrate Concentration : Reaction velocity of an enzymatic process increases with constant enzyme concentration and increase in substrate concentration.
Effect of enzyme Concentration: As there is optimal substrate concentration, rate of an enzymatic reaction or velocity (V) is directly proportional to the enzyme concentration.
Effect of product concentration In case of a reversible reaction catalyzed by a enzyme, as per the law of mass action the rate of reaction is slowed down with equilibrium. So, rate of reaction is slowed, stopped or even reversed with increase in product concentration
Effect of temperature: Velocity of enzymatic reaction increases with temperature of the medium which they are most efficient and the same is termed as optimum temperature.
Effect of pH: Many enzymes are most efficient in the region of pH 6-7, which is the pH of the cell. Outside this range, enzyme activity drops off very rapidly. Reduction in efficiency caused by changes in the pH is due to changes in the degree of ionization of the substrate and enzyme.
Highly acidic or alkaline conditions bring about a denaturation and subsequent loss of enzymatic activity
Exceptions such as pepsin (with optimum pH 1-2), alkaline phosphatase (with optimum pH 9-10) and acid phosphatase (with optimum pH 4-5)
Presence of activators Presence of certain inorganic ions increases the activity of enzymes. The best examples are chloride ions activated salivary amylase and calcium activated lipases.
Effect of Inhibitors The catalytic enzymatic reaction may be inhibited by substances which prevent the formation of a normal enzyme-substrate complex. The level of inhibition then depends entirely upon the relative concentrations of the true substrate and the inhibitor
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.
Glucagon
Glucagon, a peptide hormone synthesized and secreted from the α-cells of the islets of Langerhans of pancreas, raises blood glucose levels. The pancreas releases glucagon when blood sugar (glucose) levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream. Glucagon and insulin are part of a feedback system that keeps blood glucose levels at a stable level.
Regulation and function
Secretion of glucagon is stimulated by hypoglycemia, epinephrine, arginine, alanine, acetylcholine, and cholecystokinin.
Secretion of glucagon is inhibited by somatostatin, insulin, increased free fatty acids and keto acids into the blood, and increased urea production.
FLUORIDE
The safe limit of fluorine is about 1PPM in water. But excess of fluoride causes Flourosis
Flourosis is more dangerous than caries. When Fluoride content is more than 2 PPM, it will cause chronic intestinal upset, gastroenteritis, loss of weight, osteosclerosis, stratification and discoloration of teeth
Cholesterol synthesis:
Hydroxymethylglutaryl-coenzyme A (HMG-CoA) is the precursor for cholesterol synthesis.
HMG-CoA is also an intermediate on the pathway for synthesis of ketone bodies from acetyl-CoA. The enzymes for ketone body production are located in the mitochondrial matrix. HMG-CoA destined for cholesterol synthesis is made by equivalent, but different, enzymes in the cytosol.
HMG-CoA is formed by condensation of acetyl-CoA and acetoacetyl-CoA, catalyzed by HMG-CoA Synthase.
HMG-CoA Reductase, the rate-determining step on the pathway for synthesis of cholesterol.
The Phosphate Buffer System
This system, which acts in the cytoplasm of all cells, consists of H2PO4– as proton donor and HPO4 2– as proton acceptor :
H2PO4– = H+ + H2PO4–
The phosphate buffer system works exactly like the acetate buffer system, except for the pH range in which it functions. The phosphate buffer system is maximally effective at a pH close to its pKa of 6.86 and thus tends to resist pH changes in the range between 6.4 and 7.4. It is, therefore, effective in providing buffering power in intracellular fluids.