৪৯তম বিসিএস ⎯ প্রাণ রসায়ন [৬০১]

Explanation: (b) The inner mitochondrial membrane is impermeable to fatty acyl-CoA. The carnitine shuttle (involving CPT-I, translocase, and CPT-II) facilitates the transport of the acyl group from cytosolic CoA to mitochondrial CoA. Activation (a) happens before the shuttle. The shuttle is primarily for long-chain fatty acids; short/medium-chain (d) can diffuse in freely.

Explanation: (a) The four core steps of beta-oxidation (dehydrogenation, hydration, dehydrogenation, thiolysis) directly yield 1 FADH₂ (from the first dehydrogenase), 1 NADH (from the second dehydrogenase), and 1 acetyl-CoA (from the thiolysis step).

Explanation: (b) When beta-oxidation is high (e.g., during starvation/diabetes), large amounts of acetyl-CoA are produced. If oxaloacetate is depleted (for gluconeogenesis), acetyl-CoA cannot enter the TCA cycle and is diverted into the pathway of ketogenesis.

Explanation: (c) The brain normally relies on glucose. During prolonged fasting, it can adapt to derive up to 2/3 of its energy from ketone bodies, which helps conserve body protein by reducing the need for glucose. The liver (a) produces but cannot significantly use ketone bodies. Red blood cells (d) lack mitochondria and cannot use any fatty fuels.

Explanation: (d) Acetyl-CoA is the precursor for ketone body synthesis, not a ketone body itself. The three ketone bodies are acetoacetate, beta-hydroxybutyrate (a reduced derivative), and acetone (a spontaneous decarboxylation product of acetoacetate).

Explanation: (a) Acetyl-CoA carboxylase catalyzes the irreversible carboxylation of acetyl-CoA to form malonyl-CoA. This is the first and key regulated step that commits acetyl-CoA to fatty acid synthesis. FAS (b) then uses malonyl-CoA to build the fatty acid chain.

Explanation: (c) NADPH provides the reducing power for the synthesis steps. It is used by the beta-ketoacyl reductase and enoyl reductase enzymes of the Fatty Acid Synthase complex. The pentose phosphate pathway is a major source of NADPH.

Explanation: (c) Fatty Acid Synthase is a large multi-enzyme complex that catalyzes all the reactions to convert acetyl-CoA and malonyl-CoA into palmitate. ACC (d) produces the malonyl-CoA substrate for FAS.

Explanation: (b) Each two-carbon unit added from malonyl-CoA requires 2 NADPH (one for the reduction of the beta-keto group and one for the reduction of the enoyl group). To make a C16 fatty acid, 7 cycles are needed (the primer is an acetyl-CoA), so 7 cycles * 2 NADPH/cycle = 14 NADPH.

Explanation: (b) Malonyl-CoA, the first intermediate in fatty acid synthesis, is a potent inhibitor of CPT-I. This is a crucial regulatory mechanism to prevent simultaneous fatty acid synthesis and oxidation ("futile cycle") in the cell. When synthesis is active (high malonyl-CoA), oxidation is inhibited.

Explanation: (b) All carbon atoms in a newly synthesized fatty acid are derived from acetyl-CoA. Acetyl-CoA is carboxylated to malonyl-CoA, which serves as the actual two-carbon donor in the elongation process.

Explanation: (c) Insulin is the "fed state" hormone. It stimulates processes that store energy, like lipogenesis (fatty acid synthesis), and inhibits processes that release energy, like beta-oxidation and lipolysis.

Explanation: (c) Desaturase enzymes, such as Delta-9 desaturase, are located in the endoplasmic reticulum. They introduce double bonds using O₂ and NADH or NADPH as cofactors.

Explanation: (c) Linoleic acid (omega-6) and alpha-linolenic acid (omega-3) have double bonds at positions beyond carbon 9 (e.g., at carbon 12 and 15). Mammals lack the desaturase enzymes to create these and must obtain them from the diet, making them essential fatty acids.

Explanation: (b) All 27 carbon atoms of cholesterol are derived from acetyl-CoA. The pathway involves condensation of acetyl-CoA units to form mevalonate and then isoprenoid units.

Explanation: (a) HMG-CoA reductase converts HMG-CoA to mevalonate. This is the major point of regulation for the entire cholesterol synthesis pathway and is the target of statin drugs.

Explanation: (a) The enzymes for cholesterol synthesis are located primarily in the cytosol and the endoplasmic reticulum of the cell.

Explanation: (d) HMG-CoA reductase is regulated at multiple levels: 1) Transcriptional control: High cholesterol levels downregulate the gene. 2) Covalent modification: An AMP-activated kinase phosphorylates and inactivates it (glucagon/energy depletion signal), while an insulin-activated phosphatase dephosphorylates and activates it. Cholesterol itself does not allosterically inhibit HMG-CoA reductase (a); it regulates its expression and degradation.

Explanation: (c) HMG-CoA is a common intermediate. In the cytosol, it is used for cholesterol synthesis. In the mitochondrial matrix (from mitochondrial HMG-CoA synthase), it is used for ketone body synthesis. This compartmentalization prevents conflict between the two pathways.

Explanation: (d) Prostaglandins are eicosanoids derived from the polyunsaturated fatty acid arachidonic acid. Bile salts, steroid hormones (cortisol, estrogen, testosterone), and vitamin D are all synthesized from cholesterol.

Explanation: (b) Phospholipases are specific enzymes that hydrolyze the ester bonds in phospholipids. Different phospholipases (A1, A2, C, D) target specific bonds in the phospholipid structure.

Explanation: (b) Phospholipase A2 specifically hydrolyzes the ester bond at the *sn-2* position of a glycerophospholipid, releasing a free fatty acid (often unsaturated, like arachidonic acid) and a lysophospholipid.

Explanation: (b) Succinyl-CoA is an intermediate of the TCA cycle and can be used for gluconeogenesis. Therefore, odd-chain fatty acids are glucogenic, in contrast to even-chain fatty acids which are purely ketogenic.

Explanation: (c) The enzyme methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA, requires vitamin B₁₂ (cobalamin) as a coenzyme. A deficiency in B₁₂ leads to the buildup of methylmalonic acid.

Explanation: (b) Bile salts are amphipathic molecules that act as biological detergents. They emulsify dietary fats, breaking large lipid droplets into smaller ones, which greatly increases the surface area for enzymes like pancreatic lipase to act upon. They do not perform hydrolysis (a) but do help activate lipase (d) indirectly.

Explanation: (b) Chylomicrons are the largest lipoproteins. They are assembled in the intestinal cells to transport dietary (exogenous) triglycerides and cholesterol to peripheral tissues.

Explanation: (b) Lipoprotein Lipase, which is anchored to the capillary walls of tissues, is activated by apolipoprotein C-II, which is present on chylomicrons and VLDL. Insulin (c) promotes the synthesis of LPL.

Explanation: (b) VLDL is produced by the liver to transport endogenous triglycerides (and cholesterol) synthesized in the liver to peripheral tissues.

Explanation: (b) HDL is known as "good cholesterol" because it mediates reverse cholesterol transport—it picks up excess cholesterol from peripheral tissues and arterial plaques and returns it to the liver for excretion.

Explanation: Cystinuria is an inherited disorder of the renal tubules that prevents the reabsorption of specific amino acids from the urine. The primary defect is in the transport of cystine, which then forms insoluble crystals in the urinary tract. The transporter also handles ornithine, lysine, and arginine.

Explanation: Von Gierke's disease, or GSD I, is a disorder of carbohydrate metabolism caused by a deficiency in the enzyme glucose-6-phosphatase. This enzyme is essential for the final step of gluconeogenesis and glycogenolysis, allowing the release of free glucose into the blood. Its absence leads to hypoglycemia and a buildup of glycogen in the liver and kidneys.

Explanation: GM1 gangliosidosis is a lysosomal storage disorder caused by a genetic deficiency of the enzyme β-galactosidase. This leads to the buildup of gangliosides, primarily GM1, in the brain and other tissues.

Explanation: MSUD is a metabolic disorder caused by a defect in the branched-chain α-keto acid dehydrogenase complex, which breaks down the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine. The name "maple syrup urine disease" comes from the distinct sweet odor of the urine, sweat, and earwax of affected individuals due to the buildup of these keto acids.

Explanation: Gaucher's disease is a lysosomal storage disease caused by a genetic deficiency in the enzyme glucocerebrosidase. This leads to the accumulation of glucocerebroside, a fatty substance, in macrophages.

Explanation: Hypercholesterolemia is a condition characterized by high levels of cholesterol in the blood. While other lipids may also be elevated, the primary diagnostic marker is high cholesterol.

Explanation: Type 2 diabetes is a chronic condition characterized by insulin resistance, where the body's cells don't respond effectively to insulin. This is often accompanied by a relative insulin deficiency, as the pancreas struggles to produce enough insulin to overcome the resistance.

Explanation: Tay-Sachs disease is a lysosomal storage disorder caused by a deficiency in the enzyme hexosaminidase A. This enzyme is required to break down gangliosides, specifically GM2 ganglioside, which then accumulates in the brain and nervous system, leading to progressive neurological deterioration.

Explanation: Hereditary fructose intolerance is an autosomal recessive disorder caused by a deficiency in the enzyme aldolase B, which is essential for the breakdown of fructose. This leads to the accumulation of fructose-1-phosphate, which can cause severe hypoglycemia and liver damage.

Explanation: Classic galactosemia is an autosomal recessive disorder caused by a deficiency in the enzyme galactose-1-phosphate uridyltransferase (GALT). This enzyme is crucial for the metabolism of galactose, and its deficiency leads to a toxic buildup of galactose-1-phosphate.

Explanation: Familial hypercholesterolemia (FH) is a genetic disorder caused by a mutation in the LDL receptor gene (or, less commonly, other genes involved in LDL metabolism). This defect results in a reduced ability to remove low-density lipoprotein (LDL), or "bad" cholesterol, from the blood.

Explanation: Niemann-Pick disease is a group of inherited metabolic disorders characterized by a deficiency in the enzyme sphingomyelinase. This leads to the accumulation of sphingomyelin, a type of fatty substance, in the cells of the body, particularly the spleen, liver, and brain.

Explanation: (a) The mitochondrial membrane is impermeable to acetyl-CoA. Acetyl-CoA is condensed with oxaloacetate to form citrate, which can exit via the tricarboxylate transporter. In the cytosol, ATP-citrate lyase cleaves citrate back into acetyl-CoA (for synthesis) and oxaloacetate. This is the primary source of cytosolic acetyl-CoA. The malic enzyme reaction (converting malate to pyruvate) associated with this shuttle does generate NADPH (c), but the primary function of the shuttle itself is acetyl-CoA transport.