Rate-limiting enzymes: activators and inhibitors

Pathway	Control point	Activated by	Inhibited by
RAAS	Renin	Low renal perfusion, low NaCl at the macula densa, sympathetic tone	High blood pressure, angiotensin II feeding back, ANP
Menstrual cycle	GnRH pulse generator	Pulsatile release; sustained high estrogen (the LH surge)	Estrogen + progesterone together (hormonal contraception); constant, non-pulsatile GnRH
Stress axis (HPA)	CRH release	Stress, circadian dawn peak	Cortisol feedback; exogenous steroids (dexamethasone)
Thyroid axis (HPT)	TSH release	TRH; cold exposure and energy demand	T₃ and T₄ feedback
Glycolysis	Phosphofructokinase-1	AMP, fructose-2,6-bisphosphate	ATP, citrate
Gluconeogenesis	Fructose-1,6-bisphosphatase	Citrate	AMP, fructose-2,6-bisphosphate
TCA cycle	Isocitrate dehydrogenase	ADP, Ca²⁺	ATP, NADH
Pentose phosphate pathway	Glucose-6-phosphate dehydrogenase	NADP⁺	NADPH
Glycogen synthesis	Glycogen synthase	Insulin, glucose-6-phosphate	Glucagon, epinephrine
Glycogen breakdown	Glycogen phosphorylase	Glucagon, epinephrine, AMP	Insulin, ATP, glucose-6-phosphate
Fatty acid synthesis	Acetyl-CoA carboxylase	Insulin, citrate	Glucagon, palmitoyl-CoA
β-Oxidation	Carnitine acyltransferase I	Glucagon (low malonyl-CoA)	Malonyl-CoA
Cholesterol synthesis	HMG-CoA reductase	Insulin	Cholesterol, statins
Ketogenesis	HMG-CoA synthase	Glucagon, high acetyl-CoA	Insulin
Urea cycle	Carbamoyl phosphate synthetase I	N-acetylglutamate	None
Pyruvate → acetyl-CoA	Pyruvate dehydrogenase	Insulin, ADP, Ca²⁺, pyruvate	ATP, NADH, acetyl-CoA
Calvin cycle	Rubisco	Light: stromal pH ~8, Mg²⁺, rubisco activase	Darkness, low CO₂

What is missing	Disease	Presentation
Hypothalamic GnRH neurons	Kallmann syndrome	Puberty never starts, and the patient cannot smell
Glucose-6-phosphatase	Von Gierke disease (GSD I)	Severe fasting hypoglycemia, enlarged liver, lactic acidosis, high uric acid and lipids
Muscle glycogen phosphorylase	McArdle disease (GSD V)	Exercise intolerance and cramps, dark urine after exertion, and a characteristic second wind
Glucose-6-phosphate dehydrogenase	G6PD deficiency	Episodic hemolytic anemia after fava beans, sulfa drugs, antimalarials or infection
Pyruvate kinase	Pyruvate kinase deficiency	Chronic hemolytic anemia from birth, with splenomegaly and jaundice
Medium-chain acyl-CoA dehydrogenase	MCAD deficiency	Vomiting, lethargy and coma during a fast or illness in a young child
Ornithine transcarbamoylase	OTC deficiency	Hyperammonemia, vomiting, lethargy and cerebral edema, often after a protein load
Aldolase B	Hereditary fructose intolerance	Vomiting, hypoglycemia and jaundice appearing when an infant is weaned onto fruit or sucrose
Phenylalanine hydroxylase	Phenylketonuria	Intellectual disability, seizures, fair skin and hair, and a musty body odor
Pyruvate dehydrogenase	PDH deficiency	Lactic acidosis from birth with neurological impairment, worsened by a high-carbohydrate meal
Galactose-1-phosphate uridyltransferase	Classic galactosemia	Jaundice, hepatomegaly, cataracts and E. coli sepsis in a neonate on milk
Adrenal cortex	Addison disease	Fatigue, weight loss, low blood pressure, salt craving and darkening skin
Dietary iodine	Endemic goiter	A visibly enlarged thyroid with fatigue, cold intolerance and weight gain
Lactase	Lactose intolerance	Bloating, cramps and diarrhea after dairy

Pair	How to tell them apart
Leucine vs Isoleucine	Leucine branches at Cγ (late). Isoleucine branches at Cβ (early), which gives it a second chiral center.
Aspartate vs Asparagine	Aspartate ends in a carboxylate and carries −1. Asparagine is its amide and is always neutral.
Glutamate vs Glutamine	Glutamate ends in a carboxylate and carries −1, like aspartate one carbon longer. Glutamine is its amide and is always neutral.
Glycogen synthase vs Glycogen phosphorylase	Synthase builds and answers to insulin. Phosphorylase breaks down and answers to glucagon and epinephrine.
PFK-1 vs PFK-2	PFK-1 does glycolysis step 3. PFK-2 makes fructose-2,6-bisphosphate, the regulator that turns PFK-1 on.
Hexokinase vs Glucokinase	Hexokinase is everywhere, has a low Km, and is product-inhibited. Glucokinase is liver and β-cell, high Km, and only engages when glucose is plentiful.
CPS-I vs CPS-II	CPS-I is mitochondrial and starts the urea cycle. CPS-II is cytosolic and starts pyrimidine synthesis.
Malate-aspartate shuttle vs Glycerol-3-phosphate shuttle	Malate-aspartate (liver, heart) delivers NADH, giving 32 ATP. Glycerol-3-phosphate (muscle, brain) delivers FADH₂, giving 30.
Pyruvate carboxylase vs PEP carboxykinase	Carboxylase adds CO₂ to pyruvate in the mitochondrion. Carboxykinase removes it from OAA in the cytosol.
NADH vs NADPH	NADH is for Power: it drives ATP synthesis. NADPH is for Production: reductive biosynthesis and glutathione.
Substrate-level phosphorylation vs Oxidative phosphorylation	Substrate-level transfers a phosphate directly from a molecule; it needs no oxygen. Oxidative uses the proton gradient and requires O₂ as final acceptor.
Competitive inhibition vs Noncompetitive inhibition	Competitive raises Km and leaves Vmax alone, and more substrate overcomes it. Noncompetitive lowers Vmax and leaves Km alone.
Photosystem II vs Photosystem I	PSII comes first and splits water at 680 nm (the 2s go together). PSI runs at 700 nm and makes NADPH.
Cyclic electron flow vs Linear (noncyclic) flow	Cyclic loops ferredoxin back to cytochrome b₆f for extra ATP, with no NADPH and no O₂. Linear runs water to NADPH and releases O₂.
C4 plants vs CAM plants	C4 plants separate carbon fixation in space, from mesophyll to bundle sheath. CAM plants separate it in time, opening stomata at night. Both pay extra ATP, the drought tax.
ETC inhibitors vs Uncouplers	Inhibitors (rotenone, antimycin A, cyanide, and oligomycin at ATP synthase) halt the machinery, so O₂ consumption falls. Uncouplers (2,4-DNP, thermogenin) collapse the gradient, so O₂ consumption rises and the energy leaves as heat while no ATP is made.
Cortisol vs Aldosterone	Cortisol comes from the zona fasciculata under ACTH and manages stress fuel. Aldosterone comes from the zona glomerulosa under angiotensin II and K⁺, and manages sodium. Both come from the adrenal cortex, but from different zones under different regulators.
Graves disease vs Hashimoto thyroiditis	Graves antibodies stimulate the TSH receptor: hyperthyroid, low TSH, bulging eyes. Hashimoto antibodies destroy the gland: hypothyroid, high TSH. Both are autoimmune diseases that drive the thyroid in opposite directions.
Secretin vs CCK	Secretin answers acid with pancreatic bicarbonate, resetting the duodenal pH. CCK answers fats and peptides with pancreatic enzymes and gallbladder bile.
Pepsin vs Trypsin	Pepsin works in the stomach at pH ≈ 2 and is activated by HCl. Trypsin works in the duodenum at pH ≈ 8, is activated by enteropeptidase, and arms all the other pancreatic zymogens.

Control points