U01.01.081 Rate-determining enzymes of metabolic processes*

The regulation of metabolic processes is highly controlled by specific enzymes that are sensitive to various cellular signals. These enzymes are known as rate-determining enzymes, as they control the speed and efficiency of the entire metabolic pathway. Understanding these enzymes and their regulators is crucial for success in the USMLE Step 1 exam.

Key Rate-Determining Enzymes and Their Regulators

Process	Enzyme	Positive Regulators	Negative Regulators
Glycolysis	Phosphofructokinase-1 (PFK-1)	AMP, Fructose-2,6-bisphosphate	ATP, Citrate
Gluconeogenesis	Fructose-1,6-bisphosphatase	None	AMP, Fructose-2,6-bisphosphate
TCA Cycle	Isocitrate dehydrogenase	ADP	ATP, NADH
Glycogenesis	Glycogen synthase	Glucose-6-phosphate, Insulin, Cortisol	Epinephrine, Glucagon
Glycogenolysis	Glycogen phosphorylase	Epinephrine, Glucagon, AMP	Glucose-6-phosphate, Insulin, ATP
HMP Shunt	Glucose-6-phosphate dehydrogenase (G6PD)	NADP+	NADPH
De Novo Pyrimidine Synthesis	Carbamoyl phosphate synthetase II	ATP, PRPP	UTP
De Novo Purine Synthesis	Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase	AMP, IMP, GMP	None
Urea Cycle	Carbamoyl phosphate synthetase I	N-acetylglutamate	None
Fatty Acid Synthesis	Acetyl-CoA carboxylase (ACC)	Insulin, Citrate	Glucagon, Palmitoyl-CoA
Fatty Acid Oxidation	Carnitine acyltransferase I	None	Malonyl-CoA
Ketogenesis	HMG-CoA Synthase	None	None
Cholesterol Synthesis	HMG-CoA Reductase	Insulin, Thyroxine, Estrogen	Glucagon, Cholesterol

Points to Remember

Rate-determining enzymes control the flow of metabolites through metabolic pathways and are influenced by multiple factors.
Positive regulators (e.g., AMP, insulin) increase the activity of the enzyme.
Negative regulators (e.g., ATP, glucagon) decrease the enzyme’s activity.
A detailed understanding of these enzymes and their regulators is key for comprehending metabolic control and is frequently tested on the USMLE Step 1.

Learning Objectives for USMLE Step 1

Understand the key rate-determining enzymes in major metabolic pathways.
Identify the positive and negative regulators of each enzyme.
Be able to predict the effect of changes in metabolic conditions (e.g., changes in AMP or ATP levels) on metabolic processes.

USMLE Step 1 Review Series

Curriculum

U01.01.081 Rate-determining enzymes of metabolic processes*

Key Rate-Determining Enzymes and Their Regulators

Points to Remember

Learning Objectives for USMLE Step 1

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