MCAT: Biochemistry — Metabolism Deep Dive

What is the rate-limiting enzyme of glycolysis and how is it allosterically regulated by ATP and AMP?

Phosphofructokinase-1 (PFK-1) is the rate-limiting enzyme; it is inhibited by high levels of ATP and activated by high levels of AMP.

Which molecule acts as the most potent allosteric activator of PFK-1 and an inhibitor of Fructose-1,6-bisphosphatase?

Fructose-2,6-bisphosphate (F-2,6-BP) activates PFK-1 to promote glycolysis and inhibits Fructose-1,6-bisphosphatase to stop gluconeogenesis.

In gluconeogenesis, which mitochondrial enzyme converts pyruvate to oxaloacetate, and what cofactor does it require?

Pyruvate carboxylase converts pyruvate to oxaloacetate and requires biotin (Vitamin B7) as a cofactor.

What is the primary purpose of the oxidative phase of the Pentose Phosphate Pathway (PPP)?

The primary purpose is the irreversible production of NADPH for biosynthesis and the creation of Ribose-5-phosphate for nucleotide synthesis.

Which enzyme is the rate-limiting step of the Pentose Phosphate Pathway and is inhibited by high levels of NADPH?

Glucose-6-phosphate dehydrogenase (G6PD).

How does Malonyl-CoA regulate fatty acid metabolism?

Malonyl-CoA, an intermediate of fatty acid synthesis, inhibits Carnitine Acyltransferase I (CAT-1), preventing the entry of fatty acids into the mitochondria for beta-oxidation.

Where does fatty acid synthesis occur in the cell, and what is the primary starting substrate?

Fatty acid synthesis occurs in the cytosol and starts with Acetyl-CoA (transported out of the mitochondria as citrate).

What are the three primary ketone bodies produced during prolonged fasting, and which one cannot be used for energy?

Acetoacetate, 3-hydroxybutyrate, and acetone; acetone cannot be used for energy and is exhaled.

Why can the liver produce ketone bodies but cannot utilize them for energy?

The liver lacks the enzyme thiophorase (succinyl-CoA:3-ketoacid CoA transferase), which is required to activate acetoacetate into acetoacetyl-CoA.

What is the rate-limiting enzyme of the urea cycle, and in which cellular compartment is it located?

Carbamoyl phosphate synthetase I (CPS1), located in the mitochondrial matrix.