Citric Acid Cycle Flashcards
Net reaction of beta oxidation
16-C acyl + 7 CoA + 7 NAD+ + 7H20 + FAD -> 8 Acetyl CoA + 7NADH+ + 7H+ + FADH2
How many high-energy phosphates are created per turn of the TCA cycle from NADH production?
3 NADH @ 2.5 ATP/NADH = 7.5
How many high-energy phosphates are created per turn of the TCA cycle from FADH2 production?
1 FADH2 @ 1.5 ATP/FADH2 = 1.5
How many high-energy phosphates are created per turn of the TCA cycle from GTP?
1 GTP per 1 ATP = 1
Coarse control of the citric acid cycle
By levels of ADP; reoxidation of NADH and FADH2 is needed, which is coupled to ATP production. If there’s enough ATP, reoxidation will not occur and the CAC will slow
Rate limiting of the CAC
Level of ADP
Supply of acetyl CoA
Level of PDH activity and transport of fatty acids into the mitochondria
What affects oxaloacetate levels?
Biosynthetic pathways that affect the concentration of CAC intermediates
Fine control of the CAC
By allosteric inhibitors (negative feedback)
Negative feedback on citrate synthase
Succinyl CoA
Allosteric modifiers of isocitrate dehydrogenase
(+): ADP
(-): ATP and NADH
Allosteric modifiers of alpha-ketoglutarate dehydrogenase
(+): Calcium
(-): GTP/ATP, succinyl coA, NADH
In what other biosynthetic pathway is citrate involved?
Fatty acid/sterol synthesis
In what other biosynthetic pathway is alpha-ketoglutarate involved?
Amino acid synthesis
In what other biosynthetic pathway is succinyl CoA involved?
Heme production
In what other biosynthetic pathway is malate involved?
Gluconeogenesis
In what other biosynthetic pathway is oxaloacetate involved?
Amino acid synthesis
Anaplerotic reactions
“Replenishing” reactions
What replenishes AKG?
Amino acids -> glutamate
What replenishes succinyl coA?
Valine and isoleucine -> propionyl coA
What replenishes fumarate?
Amino acids
What replenishes oxaloacetate?
Aspartate and pyruvate
What replenishes pyruvate?
Amino acids
Most common form of PDH deficiency
X-linked dominant mutation of the E1 domain of the enzyme (others are autosomal recessive)
Signs of PDH deficiency
Increased plasma levels of pyruvate, lactate, and alanine, which produce a lactic acidosis
Treatment of PDH deficiency
Dietary supplementation of thiamine, carnitine, and lipoic acid
Inheritance of fumarase deficiency
Autosomal recessive disorder that is extremely rare
Symptoms of fumarase deficiency
Neurologic impairment, encephalopathy, and dystonia that develops shortly after birth
Urine high in fumarate, succinate, AKG, citrate, and malate
Treatment of fumarase deficiency
There is no effective treatment currently
Fluorocitrate
Inhibits aconitase and therefore the CAC; used as rat poison
