Pyruvate oxidation Flashcards
What are the sources of pyruvate?
Glycolysis
Alanine
Malate
Lactate
Serine
Cysteine
What are the fates of pyruvate?
Lactate
Alanine
Acetyl CoA
Oxaloacetate
How is pyruvate transported into mitochondria?
By proton symporter in aerobic conditions
What irreversible reaction is the link between glycolysis and CA cycle?
Pyruvate to Acetyl CoA by PDH complex
What are the 3 catalytic enzymes of the PDH complex?
Pyruvate dehydrogenase
Dihydrolipoyl transacetylase
Dihydrolipoyl dehydrogenase
What are the 2 regulatory enzymes of PDH complex?
PDH kinase
PDH phosphatase
What are the five coenzymes of the PDH complex?
Thiamine pyrophosphate
Lipoic acid
CoASH
FAD
NAD+
How does covalent modification regulate PDH complex?
Pyruvate dehydrogenase is phosphorylated by PDH kinase- making it inactive
How is the PDH complex regulated allosterically?
Pyruvate dehydrogenase is inhibited its products (acetyl CoA and NADH)
What activates PDH kinase?
Increased acetyl CoA
Increased NADH
What inhibits PDH kinase?
ADP
Pyruvate
What activate phosphatase?
Calcium
How does phosphatase affect PDH complex?
Removes phosphate to activate complex
What is the energy yield of the PDH complex?
2 NADH per glucose (1 per pyruvate) that go through ETC resulting in 5 ATP
What are signs of PDH complex deficiency?
Elevated of blood pyruvate, lactate, and alanine
Persistent metabolic acidosis
What are the characteristics of PDH complex deficiency?
Energy deficit
Neurological deficit
What are the clinical neurological signs of PDH complex deficiency?
Poor acquisition or loss of motor milestones
Poor muscle tone
New onset seizures
Periods of incoordination - ataxia and abnormal eye movements
Poor response to visual stimuli
Mental delay
Psychomotor delay
Growth retardation
What are the diagnostic criteria for PDH complex deficiency?
High blood lactate
High pyruvate
With or with lactic acidemia
What cofactors can you supplement to treat PDH complex deficiency?
Thiamine
Carnitine
Lipoic acid
What is the standard of care for PDH complex deficiency?
Cofactor supplementation
What is a possible treatment of PDH complex deficiency that has had minimal success?
Ketogenic diets