Create a list of all rate limiting steps in biochem for famge preapaerattion
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Rate-Limiting Steps in Biochemistry - FMGE Preparation
Sources: Lippincott Illustrated Reviews Biochemistry 8e, Harper's Illustrated Biochemistry 32e, Basic Medical Biochemistry (Clinical Approach) 6e
1. CARBOHYDRATE METABOLISM
| Pathway | Rate-Limiting Enzyme | Key Regulators |
|---|---|---|
| Glycolysis | Phosphofructokinase-1 (PFK-1) | Activated by AMP, ADP, fructose-2,6-bisphosphate; Inhibited by ATP, citrate |
| Glycolysis (also regulated) | Hexokinase / Glucokinase (liver) | Hexokinase inhibited by glucose-6-phosphate; Glucokinase induced by insulin |
| Glycolysis (also regulated) | Pyruvate kinase | Inhibited by ATP, alanine; activated by fructose-1,6-bisphosphate |
| Gluconeogenesis | Fructose-1,6-bisphosphatase | Inhibited by AMP, fructose-2,6-bisphosphate |
| Gluconeogenesis (committed step) | PEPCK (phosphoenolpyruvate carboxykinase) | Induced by glucagon, glucocorticoids; repressed by insulin |
| Glycogen synthesis | Glycogen synthase | Activated by glucose-6-phosphate, insulin (dephosphorylation); Inhibited by epinephrine/glucagon (phosphorylation) |
| Glycogenolysis | Glycogen phosphorylase | Activated by AMP, glucagon, epinephrine; Inhibited by glucose, insulin |
2. TCA CYCLE / PYRUVATE OXIDATION
| Pathway | Rate-Limiting Enzyme | Key Regulators |
|---|---|---|
| Pyruvate oxidation | Pyruvate dehydrogenase (PDH) complex | Inhibited by acetyl CoA, NADH, ATP; Activated by NAD⁺, CoA, AMP, Ca²⁺ |
| TCA cycle | Isocitrate dehydrogenase | Activated by ADP, Ca²⁺; Inhibited by ATP, NADH |
| TCA cycle (also regulated) | α-Ketoglutarate dehydrogenase | Inhibited by succinyl CoA, NADH; activated by Ca²⁺ |
3. LIPID METABOLISM
| Pathway | Rate-Limiting Enzyme | Key Regulators |
|---|---|---|
| Fatty acid synthesis | Acetyl CoA carboxylase (ACC) | Activated by citrate, insulin; Inhibited by palmitoyl CoA, glucagon, epinephrine |
| Fatty acid oxidation (β-oxidation) | Carnitine palmitoyltransferase-1 (CPT-1) | Inhibited by malonyl CoA (key link: high FA synthesis blocks FA oxidation) |
| Cholesterol synthesis | HMG-CoA reductase | Inhibited by cholesterol (feedback), statins; activated by insulin; inactivated by glucagon |
| Ketogenesis | HMG-CoA synthase (mitochondrial) | Increased by high acetyl CoA, low OAA state (e.g., fasting, diabetes) |
| Lipolysis (adipose) | Hormone-sensitive lipase (HSL) | Activated by glucagon, epinephrine (via cAMP); Inhibited by insulin |
4. AMINO ACID & NITROGEN METABOLISM
| Pathway | Rate-Limiting Enzyme | Key Regulators |
|---|---|---|
| Urea cycle | Carbamoyl phosphate synthetase I (CPS-I) | Activated ONLY by N-acetylglutamate (NAG); requires 2 ATP |
| Phenylalanine metabolism | Phenylalanine hydroxylase | Deficiency → Phenylketonuria (PKU) |
| Tyrosine to catecholamines | Tyrosine hydroxylase | Rate-limiting for dopamine, norepinephrine, epinephrine synthesis |
| Tryptophan to serotonin | Tryptophan hydroxylase | Rate-limiting for serotonin synthesis in the brain |
5. NUCLEOTIDE SYNTHESIS
| Pathway | Rate-Limiting Enzyme | Key Regulators |
|---|---|---|
| Purine synthesis (de novo) | Glutamine PRPP amidotransferase | Inhibited by AMP, GMP (feedback); requires PRPP |
| Pyrimidine synthesis (de novo) | CPS-II (carbamoyl phosphate synthetase II) | Activated by PRPP; inhibited by UTP |
| Purine degradation | Xanthine oxidase | Inhibited by allopurinol (treatment of gout) |
6. HEME / PORPHYRIN SYNTHESIS
| Pathway | Rate-Limiting Enzyme | Key Regulators |
|---|---|---|
| Heme synthesis (liver) | ALA synthase 1 (ALAS1) | Inhibited by heme (feedback); induced by drugs, steroids, fasting |
| Heme synthesis (erythroid) | ALA synthase 2 (ALAS2) | Regulated by iron availability |
Note: δ-Aminolevulinic acid (ALA) is formed from glycine + succinyl CoA. ALA synthase requires pyridoxal phosphate (vitamin B6) as cofactor.
7. STEROID / NEUROTRANSMITTER SYNTHESIS
| Pathway | Rate-Limiting Enzyme | Notes |
|---|---|---|
| Steroid synthesis | Desmolase (cholesterol side-chain cleavage enzyme) | Converts cholesterol → pregnenolone; located in inner mitochondrial membrane |
| Catecholamine synthesis | Tyrosine hydroxylase | Tyrosine → L-DOPA (rate-limiting step) |
| Serotonin synthesis | Tryptophan hydroxylase | Tryptophan → 5-hydroxytryptophan |
| Melatonin synthesis | Arylalkylamine N-acetyltransferase (AANAT) | Rate-limiting in pineal gland; controlled by darkness/light |
QUICK MEMORY TABLE (High-yield for FMGE)
| Pathway | Enzyme | Mnemonic |
|---|---|---|
| Glycolysis | PFK-1 | Physical Fitness Kills (activated by exercise signals) |
| Gluconeogenesis | Fructose-1,6-bisphosphatase | Opposite of PFK-1 |
| Glycogenolysis | Glycogen phosphorylase | Activated by Glucagon/Epinephrine |
| Glycogen synthesis | Glycogen synthase | Activated by insulin |
| FA synthesis | Acetyl CoA carboxylase | Inhibited by malonyl CoA precursor feedback |
| β-oxidation | CPT-1 | Inhibited by malonyl CoA |
| Cholesterol synthesis | HMG-CoA reductase | Statin target |
| TCA cycle | Isocitrate dehydrogenase | ATP/NADH inhibit |
| Urea cycle | CPS-I | Only activator = NAG |
| Heme synthesis | ALAS1/2 | B6-dependent |
| Purine synthesis | PRPP amidotransferase | Allopurinol → xanthine oxidase downstream |
| Catecholamine synthesis | Tyrosine hydroxylase | L-DOPA is product |
| Serotonin synthesis | Tryptophan hydroxylase | Selective for serotonergic neurons |
| Steroid synthesis | Desmolase | ACTH-regulated |
Key exam points to remember:
- PFK-1 is the single most tested rate-limiting enzyme - it is the "committed step" of glycolysis
- HMG-CoA reductase is the statin target (lovastatin, atorvastatin, etc.)
- CPS-I (urea cycle) vs. CPS-II (pyrimidine synthesis) - they are in different compartments (mitochondria vs. cytosol) and have different activators
- CPT-1 inhibition by malonyl CoA is the key mechanism linking fatty acid synthesis to β-oxidation suppression
- ALA synthase requires vitamin B6 - deficiency causes sideroblastic anemia
- PEPCK is the gluconeogenic enzyme induced by glucocorticoids (tested in Cushing's syndrome physiology)
- Lippincott Illustrated Reviews: Biochemistry 8e
- Harper's Illustrated Biochemistry 32e
- Basic Medical Biochemistry - A Clinical Approach 6e
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