presentation slide bio synthesis
TRANSCRIPT
Cataplerotic reactions: Pathways that utilize TCA cycle intermediates• Cataplerotic reactions utilize the intermediates of TCA cycle to
biosynthesize important products such as glucose, fatty acids and amino acids.
• Cataplerotic reactions also required to prevent inappropriate accumulation of TCA cycle intermediates in mitochondrion.
• Cataplerotic reactions occurs in 3 major pathways:
Cataplerotic Reactions
Glucose Biosynthesis
Fatty Acid Biosynthesis
Amino Acid Biosynthesis
1. Biosynthesis of Glucose: Gluconeogenesisa) Transport of oxaloacetate out of mitochondrion:• Gluconeogenesis uses oxaloacetate in TCA cycle.• Gluconeogenesis is cytosolic process, but oxaloacetate cannot transported put
of mitochondrion, hence must be converted to malate or aspartate by malate dehydrogenase and aspartate dehydrogenase respectively.
• Malate or aspartate are converted back to oxaloacetate after entering cytosol.• Oxaloacetate-malate-oxaloacetate conversion also transfers NADH reducing
equivalent from mitochondrion to cytosol.• The cytosolic NADH produced through the reduction of NAD+ in conversion of
malate back to oxaloacetate in cytosol.• Cytosolic NADH is required for gluconeogenesis.
b) PEPCK Mechanism:• Oxaloacetate is then decarboxylated and phosphorylated to PEP by PEP
caboxykinase(PEPCK), PEP is then converted to pyruvate.• The next steps are in reverse of glycolysis, which will finally yield glucose.
2. Biosynthesis of Fatty Acid• Biosynthesis of fatty acid requires acetyl-CoA, which is generated from
citrate(the intermediate of TCA cycle) as mt-membrane is impermeable to acetyl-CoA.
• Citrate can across the mt-membrane into cytosol via Tricarboxylate transport system.
• In cytosol, citrate is converted to oxaloacetate by ATP-citrate lyase: Citrate + CoA-SH + ATP Oxaloacetate + Acetyl-CoA + ADP + Pi• Oxaloacetate is then reduced to malate via oxidation of NADH by malate
dehydrogenase: Oxaloacetate + NADH + H+ Malate + NAD+• Malate is then oxidatively decarboxylated to pyruvate, via reduction of NADP+,
by malic enzyme: Malate + NADP+ Pyruvate + NADPH + CO2
• Pyruvate returning back to TCA cycle in mt.• The NADPH produced is also required in reductive reactions in fatty acid
biosynthesis.
Overview of Biosynthesis of Fatty Acid from Intermediate of TCA Cycle:
3. Amino Acid Biosynthesis• In biosynthesis of amino acid from the intermediates of TCA cycle, α-
ketoglutarate and oxaloacetate are used as the intermediates for starting materials via transamination.
• α-ketoglutarate can be converted to glutamate via reductive amination by glutamate dehydrogenase:
α-ketoglutarate + NADH + H+ + NH4+ Glutamate + NAD+ + H2O• α-ketoglutarate can also receiving –NH3+ group from another amino acid,
producing glutamate and a α-keto acid derived from the reactant amino acid.• Oxaloacetate can also receives the –NH3+ from glutamate, producing α-
ketoglutarate and aspartate.• Oxaloacetate can transaminated with alanine, forming aspartate and pyruvate in
which the –COOH is transferred to alanine.
+ -ketoglutarate+ glutamate
Aspartate aminotransferase (glutamate-oxaloacetate transaminase)
NH2 Aspartate
HOOC-CH-CH2COOH
Oxaloacetate
HOOC-CO-CH2COOH
Alanine aminotransferase (glutamate-pyruvate transaminase)
+ -ketoglutarate+ glutamate
NH2 Alanine
HOOC-CH-CH3
Pyruvate
HOOC-CO-CH3
Overview of Intermediates of TCA Cycle as Precursor of Biosynthesis of Other Products: