NEET MDS Lessons
Biochemistry
Acids and bases can be classified as proton donors and proton acceptors, respectively. This means that the conjugate base of a given acid will carry a net charge that is more negative than the corresponding acid. In biologically relavent compounds various weak acids and bases are encountered, e.g. the acidic and basic amino acids, nucleotides, phospholipids etc.
Weak acids and bases in solution do not fully dissociate and, therefore, there is an equilibrium between the acid and its conjugate base. This equilibrium can be calculated and is termed the equilibrium constant = Ka. This is also referred to as the dissociation constant as it pertains to the dissociation of protons from acids and bases.
In the reaction of a weak acid:
HA <-----> A- + H+
the equlibrium constant can be calculated from the following equation:
Ka = [H+][A-]/[HA]
As in the case of the ion product:
pKa = -logKa
Therefore, in obtaining the -log of both sides of the equation describing the dissociation of a weak acid we arrive at the following equation:
-logKa = -log[H+][A-]/[HA]
Since as indicated above -logKa = pKa and taking into account the laws of logrithms:
pKa = -log[H+] -log[A-]/[HA]
pKa = pH -log[A-]/[HA]
From this equation it can be seen that the smaller the pKa value the stronger is the acid. This is due to the fact that the stronger an acid the more readily it will give up H+ and, therefore, the value of [HA] in the above equation will be relatively small.
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.
Parathyroid Hormone
Parathyroid hormone (PTH), parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands.
It acts to increase the concentration of calcium (Ca2+) in the blood, whereas calcitonin (a hormone produced by the parafollicular cells of the thyroid gland) acts to decrease calcium concentration.
PTH acts to increase the concentration of calcium in the blood by acting upon the parathyroid hormone 1 receptor (high levels in bone and kidney) and the parathyroid hormone 2 receptor (high levels in the central nervous system, pancreas, testis, and placenta).
Effect of parathyroid hormone in regulation of serum calcium.
Bone -> PTH enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH forming new osteoclasts, which ultimately enhances bone resorption.
Kidney -> PTH enhances active reabsorption of calcium and magnesium from distal tubules of kidney. As bone is degraded, both calcium and phosphate are released. It also decreases the reabsorption of phosphate, with a net loss in plasma phosphate concentration. When the calcium:phosphate ratio increases, more calcium is free in the circulation.
Intestine -> PTH enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. PTH converts vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin.
Applications of the Henderson-Hasselbalch equation
• Calculate the ratio of CB to WA, if pH is given
• Calculate the pH, if ratio of CB to WA is known
• Calculate the pH of a weak acid solution of known concentration
• Determine the pKa of a WA-CB pair
• Calculate change in pH when strong base is added to a solution of weak acid. This is represented in a titration curve
• Calculate the pI
LIPOPROTIENS
Lipoproteins Consist of a Nonpolar Core & a Single Surface Layer of Amphipathic Lipids
The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules .These are oriented so that their polar groups face outward to the aqueous medium. The protein moiety of a lipoprotein is known as an apolipoprotein or apoprotein,constituting nearly 70% of some HDL and as little as 1% of Chylomicons. Some apolipoproteins are integral and cannot be removed, whereas others can be freely transferred to other lipoproteins.
There re five types of lipoproteins, namely chylomicrons, very low density lipoproteins(VLDL) low density lipoproteins (LDL), high density Lipoproteins (HDL) and free fatty acid-albumin complexes.
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.
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.