Biochem Ch 18
acetyl coa structure
-acetyl group has 2 Cs
-CoA has reactive S acetyl attaches to
where does pyruvate get converted to acetyl coa
-mitochondria
-have to get pyruvate into matrix where pyruvate dehydrogenase is
-irreversible reaction (acetyl coa committed to going through TCA cycle)
-regulation at this step is really important
pyruvate dehydrogenase net reaction
pyruvate + CoA + NAD+ --> acetyl CoA + CO2 + NADH + H+
steps of pyruvate to acetyl coa
-decarboxylation
-oxidation
-transfer to coa
-regeneration
what does pyruvate decarboxylation require
-5 cofactors
-thiamine/B1, lipoamide, CoA, FADH2, and NADH
-complex with 1 E1, 2 E2, and 1 E3
E1
-pyruvate dehydrogenase component
-catalyzes oxidative decarboxylation of pyruvate
-prosthetic group is TPP
-pyruvate loses CO2 and is attached to TPP, get hydroxyethyl-TPP intermediate
E2
-dihydrolipoyl transacetylase
-catalyzes transfer of acetyl to coa
-prosthetic group is lipoamide (swinging arm, interacts with E1 to accept intermediate
and swings to interact with E3 after oxidation)
E3
-dihydrolipoyl dehydrogenase
-catalyzes regeneration of oxidative form of lipoamide
-prosthetic group is FAD (reoxidizes dihydrolipoamide back to lipoamide, is reduced
to FADH2)
-electrons from FADH2 then transferred to NAD+ to produce NADH
, decarboxylation
-catalyzed by E1
-pyruvate combines with ionized (carbanion) TPP through nucleophilic attack
-forms hydroxyethyl-TPP intermediate
-irreversible (pyruvate is committed to TCA)
where is TPP derived from
-thiamine (B1)
-strip off H to get carbanion which can attack pyruvate
TPP structure
oxidation
-hydroxyethyl group attached to TPP is oxidized to form acetyl group and
simultaneously transferred to lipoamide
-disulfide group of lipoamide is reduced to disulfhydryl
-catalyzed by E1
-yields acetyl-lipoamide
lipoamide structure
-2 highly reactive sulfurs grab acetyl group
-long arm swings them around
-derived from lipoic acid when attached to lysine side chain in E2
-has some hydrophobicity
acetyl coa structure
-acetyl group has 2 Cs
-CoA has reactive S acetyl attaches to
where does pyruvate get converted to acetyl coa
-mitochondria
-have to get pyruvate into matrix where pyruvate dehydrogenase is
-irreversible reaction (acetyl coa committed to going through TCA cycle)
-regulation at this step is really important
pyruvate dehydrogenase net reaction
pyruvate + CoA + NAD+ --> acetyl CoA + CO2 + NADH + H+
steps of pyruvate to acetyl coa
-decarboxylation
-oxidation
-transfer to coa
-regeneration
what does pyruvate decarboxylation require
-5 cofactors
-thiamine/B1, lipoamide, CoA, FADH2, and NADH
-complex with 1 E1, 2 E2, and 1 E3
E1
-pyruvate dehydrogenase component
-catalyzes oxidative decarboxylation of pyruvate
-prosthetic group is TPP
-pyruvate loses CO2 and is attached to TPP, get hydroxyethyl-TPP intermediate
E2
-dihydrolipoyl transacetylase
-catalyzes transfer of acetyl to coa
-prosthetic group is lipoamide (swinging arm, interacts with E1 to accept intermediate
and swings to interact with E3 after oxidation)
E3
-dihydrolipoyl dehydrogenase
-catalyzes regeneration of oxidative form of lipoamide
-prosthetic group is FAD (reoxidizes dihydrolipoamide back to lipoamide, is reduced
to FADH2)
-electrons from FADH2 then transferred to NAD+ to produce NADH
, decarboxylation
-catalyzed by E1
-pyruvate combines with ionized (carbanion) TPP through nucleophilic attack
-forms hydroxyethyl-TPP intermediate
-irreversible (pyruvate is committed to TCA)
where is TPP derived from
-thiamine (B1)
-strip off H to get carbanion which can attack pyruvate
TPP structure
oxidation
-hydroxyethyl group attached to TPP is oxidized to form acetyl group and
simultaneously transferred to lipoamide
-disulfide group of lipoamide is reduced to disulfhydryl
-catalyzed by E1
-yields acetyl-lipoamide
lipoamide structure
-2 highly reactive sulfurs grab acetyl group
-long arm swings them around
-derived from lipoic acid when attached to lysine side chain in E2
-has some hydrophobicity
