Biochemistry - MCQ Practice Questions

Familial hypercholesterolemia results from defective LDL receptors, leading to severely elevated LDL cholesterol (200-1000 mg/dL). This causes premature atherosclerosis, xanthomas, and corneal arcus. The defect prevents normal clearance of LDL from circulation.

Palmitate (16 carbons) undergoes 7 cycles of beta-oxidation (n/2 - 1), each producing one acetyl-CoA. The final cycle releases 2 acetyl-CoA molecules, totaling 8 acetyl-CoA. Each 2-carbon unit is released as acetyl-CoA.

Niemann-Pick disease Type A is caused by deficiency of acid sphingomyelinase, leading to accumulation of sphingomyelin and cholesterol in lysosomes of various tissues, particularly the CNS, liver, and spleen. It presents with hepatosplenomegaly and neurological deterioration.

The E4/E4 genotype carries the highest genetic risk for late-onset Alzheimer's disease. ApoE4 is less efficient at clearing amyloid-beta and is associated with increased neuroinflammation. E4 carriers show earlier cognitive decline compared to E2 and E3 carriers.

Linoleic acid (omega-6 PUFA) is essential because humans lack the enzyme delta-12 desaturase needed to introduce double bonds beyond carbon-9. Only plant-based sources provide linoleic and alpha-linolenic acids. Other fatty acids can be synthesized de novo.

Sterol 27-hydroxylase catalyzes the side-chain oxidation of cholesterol to form bile acid precursors. Its deficiency or dysfunction leads to cholestanol accumulation and neuropathy. Elevated cholestanol is a characteristic finding in sterol 27-hydroxylase deficiency.

In the fed state, high citrate levels allosterically activate ACC, and insulin signaling causes PKB/Akt to phosphorylate and activate ACC. This promotes fatty acid synthesis. Conversely, AMPK phosphorylation inactivates ACC during energy deprivation.

VLDL triglyceride content increases during increased hepatic triglyceride synthesis (fed state, fatty liver). HDL is the smallest and most dense; chylomicrons have the lowest protein percentage; LDL particle size varies (pattern A = large, pattern B = small and dense).

Severe hypertriglyceridemia with eruptive xanthomas and lipemia retinalis indicates predominantly elevated chylomicrons and/or VLDL. This is seen in Type I (lipoprotein lipase deficiency), Type IV (VLDL overproduction), or Type V hyperlipoproteinemia.

Unsaturated fatty acids with cis double bonds introduce kinks in the carbon chain, preventing tight packing and increasing membrane fluidity. Cholesterol and saturated fatty acids decrease fluidity. Temperature and cholesterol content can be modulated to maintain optimal fluidity.

Sterol 7-alpha-hydroxylase catalyzes the first committed step of bile acid synthesis, forming 7-alpha-hydroxycholesterol from cholesterol. This is the rate-limiting step and is regulated by feedback inhibition by bile acids and activation by cholesterol.

ApoB-48 is the truncated form of apoB synthesized in intestinal enterocytes and is essential for chylomicron assembly and secretion. Its deficiency causes abetalipoproteinemia, characterized by fat malabsorption and severe deficiency of fat-soluble vitamins.

Cholesterol is the universal precursor for steroid hormone synthesis (cortisol, testosterone, estrogen) and bile acid synthesis. The side-chain cleavage enzyme (P450scc) catalyzes the first committed step of hormone synthesis, while 7-alpha-hydroxylase initiates bile acid synthesis.

Lipoprotein(a) levels are predominantly determined by genetic variations in the LPA gene, which encodes apolipoprotein(a). Smaller isoforms are associated with higher plasma Lp(a) levels and increased cardiovascular risk, independent of LDL cholesterol levels.

Dietary cholesterol intake inversely affects endogenous cholesterol synthesis through feedback inhibition of HMG-CoA reductase. However, saturated and trans fats have a greater impact on LDL cholesterol than dietary cholesterol itself. Genetic factors are the primary determinant of serum cholesterol.

Gaucher disease is caused by deficiency of glucocerebrosidase (beta-glucosidase), leading to accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Type 1 is the non-neuronopathic form with hepatosplenomegaly; Type 2 and 3 involve CNS involvement.

HDL mediates reverse cholesterol transport, removing cholesterol from peripheral tissues and arterial walls via ABCA1 and SR-BI pathways, then transferring it to the liver via CETP-mediated exchange with apoB-containing lipoproteins. Higher HDL is associated with reduced cardiovascular risk.

CYP27A1 mutations cause cerebrotendinous xanthomatosis (CTX), characterized by elevated cholestanol and cholestane triol precursors due to impaired side-chain oxidation of cholesterol. This leads to progressive neurological deterioration, cataracts, and diarrhea. Chenodeoxycholic acid therapy is beneficial.

Triglycerides are the primary storage form of lipids in adipose tissue, accounting for >95% of stored lipids. They are mobilized during energy deficit states.

HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate and is the rate-limiting step in cholesterol biosynthesis. It is inhibited by statins.