NEET MDS Lessons
Biochemistry
The amino acids buffer system
Amino acids contain in their molecule both an acidic (− COOH) and a basic (− NH2) group. They can be visualized as existing in the form of a neutral zwitterion in which a hydrogen atom can pass between the carboxyl and amino groups.
By the addition or subtraction of a hydrogen ion to or from the zwitterion, either the cation or anion form will be produced
Thus, when OH− ions are added to the solution of amino acid, they take up H+ from it to form water, and the anion is produced. If H+ ions are added, they are taken up by the zwitterion to produce the cation form. In practice, if NaOH is added, the salt H2N - CH2 - COONa would be formed. and the addition of HCl would result in the formation of amino acid hydrochloride.
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.
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
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)
BIOLOGICAL BUFFER SYSTEMS
Cells and organisms maintain a specific and constant cytosolic pH, keeping biomolecules in their optimal ionic state, usually near pH 7. In multicelled organisms, the pH of the extracellular fluids (blood, for example) is also tightly regulated. Constancy of pH is achieved primarily by biological buffers : mixtures of weak acids and their conjugate bases
Body fluids and their principal buffers
Body fluids Principal buffers
Extracellular fluids {Biocarbonate buffer Protein buffer }
Intracellular fluids {Phosphate buffer, Protein }
Erythrocytes {Hemoglobin buffer}
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.
HORMONES
A hormone is a chemical that acts as a messenger transmitting a signal from one cell to another. When it binds to another cell which is the target of the message, the hormone can alter several aspects of cell function, including cell growth, metabolism, or other function.
Hormones can be classified on three primary ways as following:
1. Autocrine: An autocrine hormone is one that acts on the same cell that released it.
2. Paracrine: A paracrine hormone is one that acts on cells which are nearby relative to the cell which released it. An example of paracrine hormones includes growth factors, which are proteins that stimulate cellular proliferation and differentiation.
3. Endocrine: An endocrine hormone is one that is released into the bloodstream by endocrine glands. The receptor cells are distant from the source. An example of an endocrine hormone is insulin, which is released by the pancreas into the bloodstream where it regulates glucose uptake by liver and muscle cells.