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Limiting Step Enzyme Substrate Product


Glycolysis – well fed state Fructose-6-PO4 → Fructose 1,6- Phosphofructokinase-1 Use ATP Glucose 2 Pyruvate or Lactate
Cytosol Bisphosphate

Gluconeogenesis – fasting state Fructose 1,6 Bisphosphate → Fructose 1,6-Bisphosphatease Synthesis of glucose ü Intermediates from Glycolysis Glucose
and TCA
Liver(90%), kidney (10%): Fructose-6-PO4 requires: ü Glycerol, proprionyl CoA from
6 ATP TAG
ü Lactate from Cori cycle
Mitochondria, cytosol 2 NADH ü Carbon skeleton from
from B-oxidation glucogenic AA

Kreb’s Cycle Isocitrate → α-ketoglutarate Isocitrate dehydrogenase Acetyl CoA 2 CO2


Mitochonrial matrix 1 GTP
Except succinyl dehydrogenase – inner 3 NADH
mitochondrial membrane 1 FADH2
Pentose Phosphate Oxidative Phase: Glucose-6-PO4 Dehydrogenase Produce NADPH Glucose-6-Phosphate Ribose-5-PO4
Pathway/HMP Shunt Glucose-6-PO4 → NADPH
RBC and tissues that produce lipids: liver, 6-Phosphogluconate Non oxidative Phase: (not rate limiting step) Fructose-6-PO4
adipose, adrenal, thyroid, testes, lactating Enzyme: Transketolase
mammaries Glyceraldehyde-3-PO4
Co-factor: Vit B1
Cytosol
Glycogenesis – well fed state Elongation of glycogen chains Glycogen synthase α-D,Glucose Glycogen
Liver/Muscle: Cytosol α(1-4) glycosidic bonds formation

Glycogenolysis – fasting state Shortening of glycogen chains Glycogen phosphorylase Glycogen Glucose in liver
Liver/Muscle: Cytosol α(1-4) glycosidic bonds cleavage Cofactor: Vit B6 Glucose-6-Phosphate in
muscle
Lipogenesis Acetyl CoA + HCO3 → Malonyl Acetyl CoA carboxylase Use ATP Acetyl CoA Palmytoyl-CoA
Cytosol CoA Co-enzyme: BIOTIN Must be transported from the
Activated by: Citrate and mitochondria to the cytosol
insulin via citrate shuttle
Inhibited by: glucagon and EPI
Beta Oxidation Translocation of fatty-acyl CoA Carnitine-palmitoyl transferase Palmitate 8 Acetyl CoA (even) or
Mitochonria from cytosol to mitochondria Propionyl CoA+ Acetyl
FA must be activated 1st by enzyme: CoA (odd)
Fatty Acyl Coa Synthetase + 2ATP in the 7 NADH
cytosol
7 FADH2
Ketogenesis Acetoacetyl CoA + Acetyl CoA → HMG CoA Synthase Acetyl CoA Acetoacetate
Liver mitochondria HMG CoA From B oxidation Acetone
β-hydroxybutyrate
Cholesterol Synthesis HMG CoA → Mevalonate HMG CoA Reductase Requires 2 NADPH Acetyl CoA Cholesterol
Cytosol and ER
All tissues
Urea Cycle NH3 + CO2 → Carbamoyl Carbamoyl Phosphate Synthase I Use 2 Mg-ATP NH3 Urea
Liver only: mitochondri & cytosol Phosphate Activator: N-AGA Aspartate
(N-Acetylglutamate) CO2
Heme Metabolism Glycine + Succinyl CoA → δ- ALA synthase Co-factor: Pyridoxime Heme
Aminolevulinic acid

Nucleotide: PRPP + Glutamine → 5-phospho- PRPP Glutamyl Aminotransferase PRPP IMP → GMP
PURINE Synthesis B-D-ribosylamine IMP → AMP

Nucleotide: CO2 + Glutamine + ATP → Carbamoyl Phosphate II PRPP UMP → UTP → CTP
PYRIMIDINE Synthesis Carbamoyl Phosphate UMP → dUMP →TMP

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