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General Notes * before regulator means enzyme is phosphorylated by a kinase (*PKA = Phosphorylated by Protein Kinase A) * after regulator means enzyme is dephosphorylated Ca2+ regulates by associating with calmodulin....Ca2+-Calmodulin complex mediates effects. Assume regulation by PKA is part of the Glucagon pathway.
ENZYME/PROTEIN
ACTIVATION GLYCOLYSIS
INHIBITION
COMMENTS
Glucose-6-P Glucose-6-P ATP Citrate PEP Low pH PEP Citrate *PKA ATP *PKA Lactate Pyruvate CoA / NAD+ / ADP Ca2+ / Mg2+ Acetyl CoA NADH ATP Cori Cycle (liver) Lactate-->Pyruvate KNOW MECHANISM Requires TPP, Lipoic Adic, FAD Regulated by PDH Kinase and PDH Phosphatase TCA CYLCLE Only in Liver Low pH - such as in anaerob. glycolysis (lactic acid) F-6-P <--> F-2,6-BP Not a Glycolytic Enzyme...Provides allosteric effector
PFK-2
AMP
Pyruvate Kinase
F-1,6-BP
LDH PDH
ENZYME/PROTEIN Malate DH
ACTIVATION
INHIBITION NADH
COMMENTS
GLUCONEOGENESIS Pyruvate Carboxylase PEPCK Acetyl CoA Requires Biotin Induced by Glucagon OAA --> PEP (OAA exits mitochondria as either Asp or Malate) F-bis-Phospatase G-6-Phosphatase Citrate F-2,6-BP Induced by Glucagon Only in Liver Induced by Glucagon Deficiency - von Gierkes Disease GLYCOGEN SYTHESIS / DEGRADATION Glycogen Synthase Kinase Glycogen Synthase Protein Phosphatase* *PKB Inactivation by Insulin Pathway....leads to activation of Glycogen Synthase
*PKA Ca2+
FATTY ACID / TG SYNTHESIS Citrate Lyase Malic Enzyme Acetyl CoA Carboxylase Citrate Phosphatase* (Insulin Pathway) Palmitoyl CoA *AMP-activated Protein Kinase
ENZYME/PROTEIN FA Synthase Fatty Acyl CoA Synthetase CPT-I Glycerol Kinase LPL
ACTIVATION
INHIBITION
COMMENTS
Malonyl CoA
ApoCII
FATTY ACID OXIDATION HSL Fatty Acyl CoA Synthetase *PKA FA --> FAcyl CoA ATP-->AMP + 2P(i) (Loss of TWO high energy phosphates.... remember when calculating energy yield) B-Oxidation Spiral Enzymes NADH FAD(2H) 1) 2) 3) Acyl CoA DH Enoyl CoA Hydratase B-Hydroxy Acyl CoA DH 4) B-Keto Thiolase
KETONE BODY METABOLISM Thiolase HMG-CoA Sythase HMG-CoA Lyase B-Hydroxybutyrate DH Succinyl CoA : AACoA transferase
Sequence of Events Increased [FA] in cytosol [Malonyl CoA] decreased Increased import of FA into Mitochondria Increased B-Oxid. Increase ATP Increased NADH Build up of Acetyl CoA Acetyl CoA diverted from TCA to Ketone Bodies Lowering [FA] Reversal of <-------Previous
Basically, ketone bodies are formed in the mitochondrial matrix when acetyl CoA is being produced faster than it can be oxidized in the TCA cycle. So KBs can be correlated with high [FA] With restoration to normal [FA] ....KB synthesis stops because Acetyl CoA prefers to go to TCA cycle.