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FoundSci I Unit 3 > Acetyl-CoA > Flashcards

Acetyl-CoA Flashcards

1
Q

What is the structure of acetyl-CoA?

A

Comprises coenzyme A (CoA) plus an acetyl group attached via a reactive thiol group

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2
Q

What are the sources of acetyl-CoA?

A
  1. Glucose to Pyruvate via glycolysis and pyruvate to acetyl-CoA via oxidative decarboxylation
  2. Certain amino acids to pyruvate via deamination and oxidation and pyruvate to acetyl-CoA via oxidative decarboxylation
  3. Fatty acids to acetyl-CoA via Beta-oxidation
  4. Certain amino acids to acetyl-CoA via deamination and oxidation
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3
Q

What are the fates of acetyl-CoA?

A
  1. Fat
  2. Ketone Bodies
  3. Oxidation via TCA cycle
  4. Cholesterol
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4
Q

Pyruvate dehydrogenase complex

A

Large enzymes that contains:

  • pyruvate decarboxylase (E1)
  • dihydrolipoyl transacetylase (E2)
  • dihydrolipoyl dehydrogenase (E3)
  • E3 binding protein

Converts pyruvate to acetyl-CoA via oxidative decarboxylation

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5
Q

Is pyruvate oxidized or reduced by pyruvate dehydrogenase?

A

Oxidized

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6
Q

What is a key point of metabolism involving pyruvate dehydrogenase complex? Why is this important?

A

Pyruvate dehydrogenase reaction is irreversible. No way back once pyruvate converts to acetyl-CoA

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7
Q

Where is the pyruvate dehydrogenase complex found?

A

Mitochondrial matrix

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8
Q

How is pyruvate brought to the mitochondria?

A

Pyruvate generated in cytoplasm and crosses outer mitochondrial membrane via non-selective pore protein and then into the inner mitochondrial membrane via specific carrier protein

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9
Q

What are the steps in the pyruvate dehydrogenase reaction?

A
  1. E1 decarboxylates pyruvate - intermediate forms with thiamine pyrophosphate (TPP)
  2. Intermediate oxidized to acetyl group and transferred to lipoamide group of E2
  3. Acetyl group transferred to CoA-SH by E2, forming acetyl-CoA
  4. Reduced lipoamide re-oxidized by E3 (FAD-dependent enzyme)
  5. FADH2 reoxidized by E3, electrons passing to NAD+ forming NADH
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10
Q

What four different B vitamins are required for pyruvate dehydrogenase reaction?

A
  1. Thiamine (B1) - formation of TPP
  2. Riboflavin (B2) - Generation of FAD
  3. Niacin (B3) - Formation of NAD
  4. Pantothenic Acid - component of CoA-SH
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11
Q

Thiamine deficiency

A

Dietary deficiency: polished rice lacks thiamine
alcoholism - inhibits thiamine uptake and conversion to TPP

Likely involves impairment of energy metabolism

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12
Q

What steps in energy metabolism is thiamine required for?

A

Pyruvate dehydrogenase

alpha-ketoglutarate dehydrogenase complex - TCA cycle

Branched chain alpha-keto acid dehydrogenase - amino acid metabolism

Transketolase - glucose metabolism

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13
Q

Beriberi

A

Dietary thiamine deficiency

Pain and paresthesia

Wet form - patient present with symptoms of congestive heart failure

Dry form - symmetric peripheral neuropathy

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14
Q

Wernicke encephalopathy

A

Thiamin deficient patient with chronic alcoholism

CNS impairment - mental impairment, cerebellar ataxia, horizontal nystagmus, ophthalmoplegia

Treatment by administration of thiamine

Can progress to Wernicke-Korsakoff syndrome (severe learning defect)

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15
Q

Pyruvate dehydrogenase deficiency

A

Causes chronic lactic acidosis - can cause fatal lactic acidemia in neonates

Most pts experience severe neurological problems

Most common mutations impact pyruvate decarboxylase (E1)

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16
Q

What products activate pyruvate dehydrogenase kinase?

A

Acetyl-CoA and NADH

17
Q

What inactivates pyruvate dehydrogenase complex?

A

Pyruvate dehydrogenase kinase which phosphorylates the complex

18
Q

What reactivates pyruvate dehydrogenase complex?

A

Pyruvate dehydrogenase phosphatase

19
Q

What inhibits pyruvate dehydrogenase kinase?

A

ADP and Pyruvate

20
Q

When is pyruvate dehydrogenase most active and least active?

A

Least active when energy needs are low and most active when energy needs are high

21
Q

Tricarboxylic acid cycle

A

Acetyl-CoA completely oxidized and generates reduced electron carriers and GTP.

Source of biosynthetic intermediates

22
Q

What is produced from TCA cycle?

A

2 Carbon dioxide
3 NADH
FADH2
GTP
3 H
CoA-SH

23
Q

What is important to note about the carbons in the TCA cycle?

A

2 carbons come in as an acetyl group and 2 carbons leave as CO2

No net synthesis when acetyl-CoA is oxidized in TCA cycle

24
Q

How much ATP is produced in TCA cycle?

A

Oxidation of 1 mol of acetyl-CoA could yield 10 mol of ATP

25
Q

What regulates the TCA cycle?

A

Substrate availability

Citrate synthase

Isocitrate dehydrogenase

Alpha-ketoglutarate dehydrogenase complex

26
Q

How does substrate availability regulate the TCA cycle?

A

Activity of Pyruvate dehydrogenase controls one route of substrates to TCA cycle

27
Q

How does citrate synthase regulate the TCA cycle?

A

Citrate synthase regulated by available oxaloacetate

ATP, NADH, and succinyl-CoA inhibits citrate synthase

28
Q

How does isocitrate dehydrogenase regulate the TCA cycle?

A

Allosteric Activation by ADP

Potential inhibition by NADH

29
Q

How does alpha-ketoglutarate dehydrogenase complex regulate the TCA cycle?

A

Activation by ADP

Product inhibition by succinyl CoA and NADH

30
Q

Fumarase deficiency

A

Grossly elevated urinary fumarate

Extremely rare and only well characterized TCA cycle defect

31
Q

Is there any net synthesis of intermediates in TCA?

A

No! 2 carbons in as acetyl-CoA and two carbons out as CO2

32
Q

Anaplerotic reaction

A

Replenish TCA intermediates

  1. Pyruvate carboxylase
  2. Glutamate dehydrogenase
  3. Generation of succinyl-CoA
33
Q

Pyruvate carboxylase

A

Anaplerotic reaction

Coverts pyruvate to oxaloacetate

Enzyme of mitochondrial matrix. Activated by acetyl-CoA

Expressed at high levels in liver and nervous tissue - use of TCA cycle intermediates for gluconeogenesis and neurotransmitter synthesis

Contains prosthetic group formed from biotin which functions as carboxyl group carrier

34
Q

Glutamate Dehydrogenase

A

Anaplerotic reaction

Catalyzes conversion of glutamate to alpha-ketoglutarate –> fed into the TCA cycle

Enzyme important for amino acid metabolism

35
Q

Formation of succinyl-CoA

A

Propionyl-CoA produced by oxidation of odd chain fatty acids and certain amino acids. Converted to succinyl-CoA

FoundSci I Unit 3 (13 decks)

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