STEPTRACKERBIOCHEMISTRY | METABOLISM | RAPID-FIRE REVIEW

Rate-Limiting Enzymes Master Table

Every pathway's control point, what switches it on or off, and where it runs — the single most-tested table in biochemistry.

FOCUS ON
Pattern: insulin turns on storage enzymes (glycogen synthase, ACC, HMG-CoA reductase, PFK-2); glucagon/epinephrine turn on release enzymes (glycogen phosphorylase, FBPase-2, HSL). Products inhibit their own pathway (ATP, NADH, citrate, heme, cholesterol, UTP, AMP/GMP). AMP = low energy → glycolysis and glycogen breakdown go. Full context on 7.02.
PATHWAY
RATE-LIMITING ENZYME
+ ACTIVATORS · − INHIBITORS
PAGE
Glycolysis
Phosphofructokinase-1
+ AMP, F-2,6-BP · − ATP, citrate
8.01
Gluconeogenesis
Fructose-1,6-bisphosphatase
+ ATP, acetyl-CoA · − AMP, F-2,6-BP
8.04
TCA cycle
Isocitrate dehydrogenase
+ ADP · − ATP, NADH
8.03
Glycogenesis
Glycogen synthase
+ G6P, insulin, cortisol · − epinephrine, glucagon
8.07
Glycogenolysis
Glycogen phosphorylase
+ epinephrine, glucagon, AMP · − G6P, insulin, ATP
8.07
HMP shunt
Glucose-6-phosphate dehydrogenase
+ NADP⁺ · − NADPH
8.05
Pyruvate → acetyl-CoA
Pyruvate dehydrogenase (not "rate-limiting" of a pathway but key gate)
+ NAD⁺, ADP, Ca²⁺, insulin · − acetyl-CoA, NADH, ATP
8.02
De novo pyrimidines
Carbamoyl phosphate synthetase II
+ ATP, PRPP · − UTP
1.02
De novo purines
Glutamine-PRPP amidotransferase
− AMP, IMP, GMP
1.02
Urea cycle
Carbamoyl phosphate synthetase I
+ N-acetylglutamate
9.01
Fatty acid synthesis
Acetyl-CoA carboxylase
+ insulin, citrate · − glucagon, palmitoyl-CoA
10.01
Fatty acid oxidation
Carnitine acyltransferase I (CPT I)
− malonyl-CoA
10.01
Ketogenesis
HMG-CoA synthase
(↑ with glucagon, low insulin)
10.02
Cholesterol synthesis
HMG-CoA reductase
+ insulin, thyroxine, estrogen · − glucagon, cholesterol, statins
10.03
Bile acid synthesis
Cholesterol 7α-hydroxylase
− bile acids
10.03
Heme synthesis
ALA synthase
− heme, glucose
9.05
Catecholamine synthesis
Tyrosine hydroxylase
− catecholamines (feedback) · metyrosine
9.02
Steroidogenesis
Cholesterol side-chain cleavage (desmolase, CYP11A1)
+ ACTH, LH (via StAR transport)
Endocrine link

Insulin vs glucagon — enzyme switches

ENZYME
INSULIN
GLUCAGON
Glycogen synthase
On
Off
Glycogen phosphorylase
Off
On
PFK-2 (makes F-2,6-BP)
On
Off
Acetyl-CoA carboxylase
On
Off
HMG-CoA reductase
On
Off
Hormone-sensitive lipase
Off
On

Where each pathway runs

MITOCHONDRIA
CYTOSOL
BOTH
TCA, ETC, β-oxidation
Glycolysis, HMP shunt
Heme synthesis
Ketogenesis, PDH
Fatty acid synthesis
Urea cycle
CPS I
Cholesterol synthesis, CPS II
Gluconeogenesis

How it's tested

COMMON CONFUSIONHMG-CoA synthase = ketones (mitochondria); HMG-CoA reductase = cholesterol (cytosol/SER). CPS I = urea; CPS II = pyrimidines.
THE TRAPFructose-2,6-bisphosphate activates PFK-1 AND inhibits FBPase-1 — one molecule flips the liver between glycolysis and gluconeogenesis.
YOUR APPROACHName the pathway → enzyme → fed or fasting → product feedback → drug that targets it.

If you see… think…

Statins inhibit → HMG-CoA reductase
Malonyl-CoA inhibits → CPT I
N-acetylglutamate activates → CPS I
Heme and glucose repress → ALA synthase
Metyrosine inhibits → tyrosine hydroxylase
AMP activates → PFK-1, glycogen phosphorylase
Citrate activates → acetyl-CoA carboxylase; inhibits PFK-1
NADPH inhibits → G6PD
UTP inhibits → CPS II
ATP and NADH inhibit → isocitrate dehydrogenase