USMLE Step 1 Biochemistry Practice Questions

A 4-month-old infant presents with failure to thrive, hepatomegaly, hypoglycemia, lactic acidosis, and hyperuricemia. Muscle biopsy reveals glycogen accumulation with normal structure. Deficiency of which enzyme is the most likely cause of this condition (Von Gierke disease, Glycogen Storage Disease Type I)?

• (A) Glucose-6-phosphatase
• (B) Muscle glycogen phosphorylase
• (C) Debranching enzyme (alpha-1,6-glucosidase)
• (D) Lysosomal alpha-1,4-glucosidase (acid maltase)

Which metabolic pathway is the primary source of NADPH, essential for reductive biosynthesis (e.g., fatty acid and steroid synthesis) and protecting against oxidative stress (via glutathione reductase)?

• (A) Pentose Phosphate Pathway (PPP)
• (B) Glycolysis
• (C) Citric Acid Cycle (TCA Cycle)
• (D) Beta-oxidation

A patient with chronic alcoholism presents with confusion, ataxia, and ophthalmoplegia (Wernicke encephalopathy). This condition is caused by a deficiency of thiamine (Vitamin B1). Thiamine pyrophosphate (TPP) is an essential cofactor for which of the following enzymes?

• (A) Pyruvate dehydrogenase complex
• (B) Lactate dehydrogenase
• (C) Succinate dehydrogenase
• (D) Glucose-6-phosphate dehydrogenase

During prolonged fasting (greater than 12-18 hours), which process becomes the primary source of blood glucose maintenance?

• (A) Gluconeogenesis
• (B) Glycogenolysis
• (C) Beta-oxidation
• (D) Ketogenesis

Which lipoprotein particle is primarily responsible for transporting dietary triglycerides from the intestines to peripheral tissues and the liver?

• (A) Chylomicrons
• (B) Very-low-density lipoprotein (VLDL)
• (C) Low-density lipoprotein (LDL)
• (D) High-density lipoprotein (HDL)

Maple Syrup Urine Disease (MSUD) is an autosomal recessive disorder characterized by the accumulation of branched-chain amino acids (leucine, isoleucine, valine) and their corresponding alpha-ketoacids in the body. This disease results from a deficiency in which enzyme complex?

• (A) Branched-chain alpha-ketoacid dehydrogenase complex
• (B) Alanine aminotransferase (ALT)
• (C) Phenylalanine hydroxylase
• (D) Homogentisate oxidase

Which vitamin is essential for the carboxylation of glutamate residues in certain proteins (e.g., clotting factors II, VII, IX, X, protein C, protein S), enabling them to bind calcium and function properly?

• (A) Vitamin K
• (B) Vitamin D
• (C) Vitamin A
• (D) Vitamin E

A defect in the enzyme Phenylalanine Hydroxylase (PAH), or its cofactor tetrahydrobiopterin (BH4), leads to the accumulation of phenylalanine in the body. This condition is known as:

• (A) Phenylketonuria (PKU)
• (B) Alkaptonuria
• (C) Tyrosinemia Type 1
• (D) Homocystinuria

Which molecule serves as the direct precursor for the synthesis of steroid hormones (e.g., cortisol, aldosterone, testosterone, estrogen)?

• (A) Cholesterol
• (B) Acetyl-CoA
• (C) Malonyl-CoA
• (D) Pyruvate

The process of beta-oxidation, which breaks down fatty acids to generate acetyl-CoA, occurs primarily in which cellular compartment?

• (A) Mitochondria
• (B) Cytosol
• (C) Peroxisome
• (D) Endoplasmic Reticulum

Which of the following enzymes catalyzes the rate-limiting step in cholesterol synthesis?

• (A) HMG-CoA reductase
• (B) Mevalonate kinase
• (C) Acetyl-CoA carboxylase
• (D) Fatty acid synthase

Urea cycle disorders result from defects in enzymes involved in converting ammonia, a toxic byproduct of amino acid metabolism, into urea for excretion. Accumulation of ammonia leads to hyperammonemia. Which molecule directly incorporates the first nitrogen atom into the urea cycle?

• (A) Ammonia (as carbamoyl phosphate)
• (B) Aspartate
• (C) Glutamine
• (D) Alanine

Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by hyperuricemia, gout, self-mutilation, and neurological dysfunction. It is caused by a deficiency in which enzyme of purine metabolism?

• (A) Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
• (B) Adenosine deaminase (ADA)
• (C) Xanthine oxidase
• (D) PRPP synthetase

Which of the following is an essential fatty acid, meaning it cannot be synthesized by humans and must be obtained from the diet?

• (A) Linoleic acid (an omega-6 fatty acid)
• (B) Oleic acid (an omega-9 fatty acid)
• (C) Palmitic acid (a saturated fatty acid)
• (D) Stearic acid (a saturated fatty acid)

Glycolysis, the breakdown of glucose to pyruvate, occurs in the cytoplasm. Which enzyme catalyzes the first irreversible, committed step unique to glycolysis?

• (A) Phosphofructokinase-1 (PFK-1)
• (B) Hexokinase/Glucokinase
• (C) Pyruvate kinase
• (D) Glyceraldehyde-3-phosphate dehydrogenase

Collagen, the most abundant protein in the human body, requires extensive post-translational modification for proper structure and function. Hydroxylation of proline and lysine residues within procollagen chains is essential for stable triple helix formation and cross-linking. This hydroxylation requires which vitamin as a cofactor?

• (A) Vitamin C (Ascorbic acid)
• (B) Vitamin B6 (Pyridoxine)
• (C) Vitamin B12 (Cobalamin)
• (D) Vitamin A (Retinol)

Which metabolic process is directly stimulated by insulin?

• (A) Glycogen synthesis
• (B) Gluconeogenesis
• (C) Ketogenesis
• (D) Lipolysis

Fructose intolerance (Hereditary Fructose Intolerance, HFI) is caused by a deficiency in which enzyme, leading to the accumulation of fructose-1-phosphate after fructose ingestion?

• (A) Aldolase B
• (B) Fructokinase
• (C) Hexokinase
• (D) Phosphofructokinase-1 (PFK-1)

The conversion of pyruvate to acetyl-CoA, linking glycolysis to the citric acid cycle, is catalyzed by the pyruvate dehydrogenase complex. Which of the following molecules acts as an allosteric inhibitor of this complex?

• (A) Acetyl-CoA
• (B) AMP
• (C) NAD+
• (D) Pyruvate

Which type of RNA molecule carries amino acids to the ribosome and matches them to the corresponding codons on the messenger RNA (mRNA) during protein synthesis?

• (A) Transfer RNA (tRNA)
• (B) Ribosomal RNA (rRNA)
• (C) Messenger RNA (mRNA)
• (D) Small nuclear RNA (snRNA)

DNA replication is semi-conservative, meaning each new DNA molecule consists of one parental strand and one newly synthesized strand. Which enzyme is primarily responsible for synthesizing the new DNA strands during replication in prokaryotes?

• (A) DNA Polymerase III
• (B) DNA Polymerase I
• (C) Helicase
• (D) Primase

Xeroderma pigmentosum is a genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation and a high predisposition to skin cancer. This condition is caused by defects in which DNA repair mechanism?

• (A) Nucleotide Excision Repair (NER)
• (B) Base Excision Repair (BER)
• (C) Mismatch Repair (MMR)
• (D) Homologous Recombination

Which of the following amino acids is purely ketogenic, meaning its carbon skeleton can only be degraded to acetyl-CoA or acetoacetyl-CoA?

• (A) Leucine
• (B) Alanine
• (C) Glycine
• (D) Aspartate

The synthesis of fatty acids occurs in the cytosol. Which molecule provides the two-carbon units (acetyl groups) for elongation of the fatty acid chain?

• (A) Malonyl-CoA
• (B) Acetyl-CoA
• (C) Propionyl-CoA
• (D) Succinyl-CoA

Which enzyme is deficient in McArdle disease (Glycogen Storage Disease Type V), leading to exercise intolerance, muscle cramps, and myoglobinuria, but without hypoglycemia?

• (A) Muscle glycogen phosphorylase
• (B) Liver glycogen phosphorylase
• (C) Glucose-6-phosphatase
• (D) Debranching enzyme (alpha-1,6-glucosidase)

Which coenzyme form of Vitamin B6 (pyridoxine) is essential for the activity of aminotransferases (transaminases), enzymes that catalyze the transfer of amino groups between amino acids and alpha-keto acids?

• (A) Pyridoxal phosphate (PLP)
• (B) Thiamine pyrophosphate (TPP)
• (C) Flavin adenine dinucleotide (FAD)
• (D) Nicotinamide adenine dinucleotide (NAD+)

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It leads to the accumulation of carbamoyl phosphate, which then spills into the pyrimidine synthesis pathway. This results in increased urinary excretion of which compound?

• (A) Orotic acid
• (B) Uric acid
• (C) Citrulline
• (D) Argininosuccinate

Which hormone stimulates lipolysis (breakdown of triglycerides) in adipose tissue, particularly during fasting or stress?

• (A) Epinephrine (and Glucagon)
• (B) Insulin
• (C) Cortisol
• (D) Growth Hormone

A mutation in the gene encoding the LDL receptor leads to impaired uptake of LDL particles from the blood into cells. This results in significantly elevated plasma LDL cholesterol levels and premature atherosclerosis. This condition is known as:

• (A) Familial Hypercholesterolemia (FH)
• (B) Abetalipoproteinemia
• (C) Type III Hyperlipoproteinemia (Dysbetalipoproteinemia)
• (D) Lipoprotein lipase deficiency

Which complex of the electron transport chain (ETC) is also an enzyme component of the citric acid cycle?

• (A) Complex II (Succinate dehydrogenase)
• (B) Complex I (NADH dehydrogenase)
• (C) Complex III (Cytochrome bc1 complex)
• (D) Complex IV (Cytochrome c oxidase)

The synthesis of heme, the prosthetic group of hemoglobin, myoglobin, and cytochromes, begins with the condensation of which two molecules?

• (A) Succinyl-CoA and Glycine
• (B) Acetyl-CoA and Glycine
• (C) Propionyl-CoA and Alanine
• (D) Alpha-ketoglutarate and Serine

Which of the following molecules acts as the primary methyl group donor in most biological methylation reactions (e.g., synthesis of epinephrine from norepinephrine, methylation of DNA and histones)?

• (A) S-Adenosylmethionine (SAM)
• (B) Tetrahydrofolate (THF)
• (C) Vitamin B12 (Cobalamin)
• (D) Methionine

Galactosemia is an inability to properly metabolize galactose, often presenting in infancy with vomiting, jaundice, hepatomegaly, and cataracts after milk ingestion. The classic form is caused by a deficiency in which enzyme?

• (A) Galactose-1-phosphate uridyltransferase (GALT)
• (B) Galactokinase (GALK)
• (C) UDP-galactose 4-epimerase (GALE)
• (D) Lactase

Which enzyme catalyzes the oxidative deamination of glutamate, releasing ammonia and regenerating alpha-ketoglutarate, playing a central role in linking amino acid metabolism to the TCA cycle and urea cycle?

• (A) Glutamate dehydrogenase
• (B) Alanine aminotransferase (ALT)
• (C) Aspartate aminotransferase (AST)
• (D) Glutaminase

The process by which messenger RNA (mRNA) is synthesized from a DNA template is called:

• (A) Transcription
• (B) Translation
• (C) Replication
• (D) Reverse transcription

Which type of chemical bond links amino acids together to form the primary structure of proteins?

• (A) Peptide bond
• (B) Hydrogen bond
• (C) Disulfide bond
• (D) Ionic bond

Cytochrome P450 enzymes, a large family of heme-containing monooxygenases, are primarily involved in which type of metabolic reactions, particularly in the liver?

• (A) Hydroxylation (Phase I drug metabolism)
• (B) Methylation
• (C) Phosphorylation
• (D) Glycosylation

Which molecule is the end product of anaerobic glycolysis in human muscle tissue?

• (A) Lactate
• (B) Pyruvate
• (C) Ethanol
• (D) Acetyl-CoA

A deficiency in the enzyme Adenosine Deaminase (ADA) leads to the accumulation of adenosine and deoxyadenosine, which are particularly toxic to lymphocytes. This results in which severe immunodeficiency disorder?

• (A) Severe Combined Immunodeficiency (SCID)
• (B) Wiskott-Aldrich syndrome
• (C) DiGeorge syndrome
• (D) X-linked agammaglobulinemia

Which of the following vitamins is a precursor for the coenzyme Flavin Adenine Dinucleotide (FAD), which acts as an electron carrier in redox reactions (e.g., succinate dehydrogenase in TCA cycle, acyl-CoA dehydrogenase in beta-oxidation)?

• (A) Riboflavin (Vitamin B2)
• (B) Niacin (Vitamin B3)
• (C) Thiamine (Vitamin B1)
• (D) Pantothenic acid (Vitamin B5)