Pyruvate Dehyrdrogenase Complex Flashcards
What are the 5 coenzymes for pyruvate dehydrogenase complex needs for its complete catalytic activity?
- Thiamine pyrophosphate (TPP)
- Lipoate (lipoic acids)
- NAD+ (niacin derivative)
- FAD (riboflavin derivative
- Reduced coenzyme A (CoASH) (pantothenic acid derivative)
What does pyruvate decarboxylase (E1) require?
TPP
What does dihydrolipolytransacetylase (E2) require?
lipoic acid and CoA (pantothenic acid)
What does dihydrolipoyl deydrogenase (E3) require?
NAD+ (niacin) and FAD (riboflavin)
When is PDC active?
in the dephosphorylated state by PDC phosphatase
When is PDC inactive?
PDC kinase, which phosphorylates it
What is PDC kinsae inhibited by?
ADP and pyruvate
What does arsenite inhibit?
all the enzymes requiring lipoic acid as a coenzyme, including E2 of the a-ketoglutarate dehydrogenase complex
What does arsenite do?
it forms a stable complex with thiol groups of lipoic acid, making it unavailable, which leads to inefficient conversion of pyruvate to acetyl coA, so pyruvate and consequently lactic acid accumulate
- X-linked dominant
- congenital lactic acidosis
- neurodegernation, muscle spasticity, early death
Pyruvate dehydrogenase (PDH E1) deficiency
why is there brain degeneration in yruvate dehydrogenase (PDH E1) deficiency?
The brain is sensitive to acidosis due to increased conversion of pyruvate to lactate.
What occurs in Leigh Syndrome/subacute necrotizing encephalomyelopathy?
- defects in mitochondrial ATP production due to mutations in the PDH complex
- brain is unable to produce sufficient ATP since PDH complex is inactive, so thiamine or niacin deficiencies cause serious CNS problems
What are some vitamins that the TCA Cycle require to function?
niacin (NAD+), riboflavin (FAD and FMn), pantothenic acid (coenzyme A), thaimine, Mg2+, Ca2+, Fe2+, and phosphate)
What is the rate limiting enzyme for TCA cycle?
isocitrate dehydrogenase
increased levels of what activate the TCA cycle?
ADP
increased levels of what inhibits the TCA cycle?
NADH
What can citrate be removed from the TCA cycle for?
Fatty Acid Synthesis
What can alpha-ketoglutarate be removed from the TCA cycle for?
Amico Acid synthesis/neurotransmitter
What can Succinyl CoA be removed from the TCA cycle for?
heme synthesis
What can Malate be removed from the TCA cycle for?
gluconeogenesis
What can Oxaloacetate be removed from the TCA cycle for?
Amino Acid Synthesis
What is one of the major anapleurotic enzymes in the cell?
Pyruvate carboxylase
Pyruvate carboxylase is found in what tissues?
liver, brain, adipocytes, fibroblasts
Pathways that replenish the intermediates of the TCA cycle are reffered to as what
Anapleurotic - “filling up”
What enzyme converts Acetyl CoA to Citrate?
Citrate synthase
What enzyme converts Citrate to Isocitrate?
Aconitase
What enzyme converts Isocitrate to a-Ketoglutarate?
Isocitrate dehydrogenase
What enzyme converts a-Ketoglutarate to Succinyl CoA?
a-Ketoglutarate dehydrogenase
What enzyme converts Succinyl CoA to Succinate?
succinate thiokinase
What enzyme converts Succinate to Fumarate?
Succinate dehydrogenase
What enzyme converts Fumarate to Malate?
Fumarase
What enzyme converts Malate to Oxaloacetate?
Malate dehydrogenase
What is one of the major anapleurotic enzymes in the cell?
pyruvate carboxylase
What are the steps of the TCA cycle?
Acetyl CoA -> Citrate ->Isocitrate -> Alpha-ketoglutarase ->Succinyl CoA -> Succinate -> Fumarate -> Malate -> Oxaloacetate
The PDH complex converts what to what?
Pyruvate to Acetyl CoA
Which subunit binds TPP and catalyzes the decarboxylation reaction?
E1
Which subunit binds transacylase and is involved in the ox-red part of the reaction?
E2
Which subunit reduces NAD+?
E3
what does aresenite inhibit?
all the enzymes requiring lipoic acid as a coenzyme
