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GI I > Pyruvate oxidation > Flashcards

Pyruvate oxidation Flashcards

1
Q

What are the sources of pyruvate?

A

Glycolysis
Alanine
Malate
Lactate
Serine
Cysteine

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2
Q

What are the fates of pyruvate?

A

Lactate
Alanine
Acetyl CoA
Oxaloacetate

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3
Q

How is pyruvate transported into mitochondria?

A

By proton symporter in aerobic conditions

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4
Q

What irreversible reaction is the link between glycolysis and CA cycle?

A

Pyruvate to Acetyl CoA by PDH complex

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5
Q

What are the 3 catalytic enzymes of the PDH complex?

A

Pyruvate dehydrogenase
Dihydrolipoyl transacetylase
Dihydrolipoyl dehydrogenase

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6
Q

What are the 2 regulatory enzymes of PDH complex?

A

PDH kinase
PDH phosphatase

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7
Q

What are the five coenzymes of the PDH complex?

A

Thiamine pyrophosphate
Lipoic acid
CoASH
FAD
NAD+

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8
Q

How does covalent modification regulate PDH complex?

A

Pyruvate dehydrogenase is phosphorylated by PDH kinase- making it inactive

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9
Q

How is the PDH complex regulated allosterically?

A

Pyruvate dehydrogenase is inhibited its products (acetyl CoA and NADH)

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10
Q

What activates PDH kinase?

A

Increased acetyl CoA
Increased NADH

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11
Q

What inhibits PDH kinase?

A

ADP
Pyruvate

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12
Q

What activate phosphatase?

A

Calcium

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13
Q

How does phosphatase affect PDH complex?

A

Removes phosphate to activate complex

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14
Q

What is the energy yield of the PDH complex?

A

2 NADH per glucose (1 per pyruvate) that go through ETC resulting in 5 ATP

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15
Q

What are signs of PDH complex deficiency?

A

Elevated of blood pyruvate, lactate, and alanine
Persistent metabolic acidosis

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16
Q

What are the characteristics of PDH complex deficiency?

A

Energy deficit
Neurological deficit

17
Q

What are the clinical neurological signs of PDH complex deficiency?

A

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

18
Q

What are the diagnostic criteria for PDH complex deficiency?

A

High blood lactate
High pyruvate
With or with lactic acidemia

19
Q

What cofactors can you supplement to treat PDH complex deficiency?

A

Thiamine
Carnitine
Lipoic acid

20
Q

What is the standard of care for PDH complex deficiency?

A

Cofactor supplementation

21
Q

What is a possible treatment of PDH complex deficiency that has had minimal success?

A

Ketogenic diets

GI I (19 decks)

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