CAC

Question 1

Identify where in the cell pyruvate, fatty acids, and acetyl CoA are oxidized.

Answer 1

pyruvate is formed from the oxidation of glucose in the cytosol.

Pyruvate is oxidized to Acetyl-CoA in the mitochondrial matrix via the action of PDH.

Fatty acids are joined to Acetyl-CoA in the cytosol and are oxiudized to Acetyl-CoA in the mitochondrial matrix via beta-oxidation

Question 2

What is generate from the oxidation of acetyl CoA

Answer 2

3 NADH

1FADH2

1 GTP

Question 3

Where does fatty acid metabolism take place in the CAC

Answer 3

Outer membrane - fatty acid acyl-CoA synthases

Inner membrane - Carnatine: acyl CoA transferase

Matrix - Fatty acid B-oxidation

Question 4

What biosynthetic pathways do CAC intermediates serve as substrates for?

Answer 4

Citrate- fatty acid and sterol synthesis

Alpha-ketoglutarate- amino acid synthesis, neurotransmitters

Succinyl CoA - Heme

Malate - Gluconeogensis

Oxaloacetate - Amino acid synthesis

Question 5

How are CAC intermediates replenished?

Answer 5

amino acids→ pyruvate→ Acetyl coA and oxaloacetate

Amino acids→ glutamate→alpha-ketoglutarate

valine ansd isoleucine → propionyl CoA→Succinyl CoA

Amino acid→fumarate

Aspartate→Oxaloacetate

Question 6

Regulation of PDH

Answer 6

negative: NADH and Acetyl CoA

Question 7

Regulation of Isocitrate dehydrogenase

Answer 7

negative: NADH and ATP

Positive: ADP

Question 8

regulation of alpha-ketoglutarate dehydtogenase

Answer 8

positive: calcium

Negative: GTP, ATP, Succinyl CoA, NADH

Question 9

What are the fates of NADH and FADH2 produced in the CAC?

Answer 9

they are reoxidized in conjuction with the ETC to produce ATP

Question 10

What are the fates of Acetyl CoA?

Answer 10

CAC

ketone bodies

fatty acids and sterols

Question 11

What is the stoichiometry of the CAC

Answer 11

reaoxidation of 3 NADH at 2.5 ATP per NADH = 7.7

Reoxidation of 1 FADH2 at 1.5 ATP per FADH2 = 1.5

1 GTP generated = 1

10 total high energy substrates

Question 12

Descrive the role of NADH, FADH2, and ADP in course control of CAC

Answer 12

CAC is regulated by high or low energy. High energy (increase in ATP, GTP, NADH, FADH2 high cellular activity, low oxygen) inhibits the CAC

Low energy (increase in ADP, Ca2+) stimulate the CAC

Reoxidation of NADH or FADH2 is required for the CAC to continue. This reoxidation is coupled to ATP synthesis in mitochondria.** The supply of ADP for ATP synthesis is rate limiting. **

Question 13

Fine Control of CAC

Answer 13

allosteric effectors that regulate isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase.

Question 14

Describe the role of acetyl coA in course control of the CAC

Answer 14

The activity of PDH dictates how much glucose in converted to Acetyl CoA

Fatty acid oxidation to acetyl CoA depends on the availability of carnatine as well as the activity of carnitine acyl transferase-1, carnitine palmitoyl transferase-1

Question 15

PDH

Answer 15

tranforms pyruvate to acetyl CoA through pyruvate decarboxylaiton. AcCoA can then be used in the CAC to carry out cell resp. PDH links the metabolic pathway to the CAC and released energy via NADH.

PDH is made of multiple copies of E1 E2 and E3.

Question 16

PDH deficiency

Answer 16

most common form is caused by mutation in the E1 alpha gene. X-linked dominant. All others arei nherited in an X-linked recessive manner.

elevated serum lactate, pyruvate, alanine which produce chronic lactic acidosis

treatment: thiamina, carnatine, and lipoic acids

some patients treated with dichloroacetate an inhibitor of the protein kinase subunit of pyruvate dehydrogenase complex.

Question 17

Fumarase deficiency

Answer 17

autosomal recessive metabolic disorder. disrupted ability to convert fumarate to malate.

severe neurological impairment, encephalomyopathy, and dystonia soon after birth.

urine containe high: fumarate, succinate, alpha-ketoglutarate, citrate, and malate.

no effective treatment, nutritional intervention, physical therapy, and wheelchairs are useful for some.

Question 18

Rat poison

Answer 18

fluroacetate is converted to flurocitrate

inhibits aconitase and thus CAC