Biochemistry · USMLE Step 1

USMLE Biochemistry: Pathways and Enzyme Deficiencies

Metabolic pathways (glycolysis, urea cycle, etc.) and inherited enzyme deficiency diseases with the deficient enzyme and clinical clue.

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What are the net ATP and NADH products per glucose molecule in glycolysis?
2 ATP and 2 NADH (under aerobic conditions)
Which enzyme catalyzes the first committed step of glycolysis and serves as the primary rate-limiting enzyme?
Phosphofructokinase-1 (PFK-1)
Lactate dehydrogenase converts pyruvate to lactate; under what metabolic condition is this reaction especially important?
Anaerobic conditions or intense exercise
Hexokinase is inhibited by which of its own products?
Glucose-6-phosphate
Which vitamin-derived cofactor is required by pyruvate dehydrogenase complex?
Thiamine pyrophosphate (TPP), derived from vitamin B1
Pyruvate dehydrogenase complex requires five different coenzymes; name them.
TPP (thiamine pyrophosphate), NAD+, FAD, coenzyme A (CoA), and lipoic acid
The Pasteur effect describes the inhibition of glycolysis by oxygen; this allows oxygen to spare which fuel source?
Glucose
Which two organs are the major sites of gluconeogenesis?
Liver and kidney (cortex)
Why cannot acetyl-CoA serve as a net source of glucose during gluconeogenesis?
The two carbons that enter oxaloacetate as acetyl-CoA are released as CO2 during the same cycle, resulting in no net glucose synthesis
In the Cori cycle, what is the starting substrate and end product?
Starting substrate: glucose (from liver) used in muscle; end product: glucose regenerated in liver from lactate released by muscle
How many ATP equivalents does one complete turn of the citric acid cycle generate?
Approximately 10 ATP equivalents (3 NADH = 7.5 ATP, 1 FADH2 = 1.5 ATP, 1 GTP/ATP = 1 ATP)
Which enzyme in the citric acid cycle is the primary regulatory target and is inhibited by high ATP, NADH, and succinyl-CoA?
Isocitrate dehydrogenase, inhibited by high ATP and NADH and activated by ADP and Ca2+ (succinyl-CoA instead inhibits alpha-ketoglutarate dehydrogenase, the next enzyme in the cycle)
What is the only substrate-level phosphorylation step in the citric acid cycle, and which enzyme catalyzes it?
Succinyl-CoA to succinate, catalyzed by succinyl-CoA synthetase (also called succinate thiokinase)
Pyruvate carboxylase catalyzes the first gluconeogenic step (pyruvate to oxaloacetate) and requires which vitamin-derived cofactor?
Biotin (vitamin B7)
In which cellular compartment does the urea cycle primarily occur?
Mitochondrial matrix (initial step) and cytoplasm (final steps)

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