PDHC Flashcards
Pyruvate Dehydrogenase overall reaction
Pyruvate + NAD + CoA –> Acetyl-CoA + CO2 + NADH
Where is the PDHC located
mitochondrial matrix
3 parts of PDHC and their bound cofactors
1) Pyruvate Dehydrogenase (E1)
- TPP thiamine pyrophosphate
2) Dihydrolipoyl Transacetylase (E2)
- Lipoid acid (on K side chain)
3) Dihydrolipoyl Dehydrogenase (E3)
- FAD
What do these vitamins make?
Thiamine (B1)
Riboflavin (B2)
Nicotinate (Niacin)
Pantothenate
TPP
FAD
NAD
CoA
Why is the regulation of PDHC important?
Pyruvate can be converted back to glucose, but once Acetyl-CoA is made, it cannot be made into glucose
How is PDHC inhibited?
High product/reactant ratios
high Acetyl-CoA/CoA
high NADH/NAD
also PDH Kinase
PDH Kinase and how is it activated
inactivates PDH via phosphorylation of E1
- also activated by high ratios of product/reactant
- high amounts of high-energy products shut off PDHC (ATP, Acetyl-CoA, NADH)
PDH Phosphatase and how is it activated
Activates PDH via dephospho rylation of E1
- activated by insulin, pyruvate, Ca2+ (increased activity in skeletal muscles, needs more energy production)
PDH Deficiency
deficiency in the ⍺ subunit of the E1 gene (not transported into the mitochondria)
- causes pyruvate to be shunted to lactate
- results in lactic acidosis
- X-linked
- neurological defects
- increase in alanine and lactate
How is PDH deficiency treated?
Dichloroacetate, inhibits PDH kinase
Thiamine diet -> helps produce TPP
Ketogenic diet -> acetyl-CoA via ß-ox, bypass PDH
Function of E1 (Pyruvate Dehydrogenase)
1) Decarboxylate Pyruvate and load TPP releasing CO2
2) Load Lipoid acid and release TPP
Function of E2 (Dihydrolipoyl Transacetylase)
Forms acetyl-CoA and releases dihydrolipoic acid
Function of E3 (Dihydrolipoyl dehydrogenase)
1) Reform Lipoid acid from dihydrolipoic acid via reduction of FAD to FADH2
2) Oxidize FADH2 back to FAD via NAD to NADH
What inhibits PDH Kinase?
High concentrations of Pyruvate
Which 4 PDHC cofactors come from the diet?
NAD
FAD
TPP
CoA
