AC Lecture 63: Krebs Citric Acid Cycle Flashcards
What is the purpose of the TCA cycle?
extraction of most of the energy for cells
Where does the TCA cycle occur?
the mitochondrial matrix compartment of all cells
What is the net reaction of the TCA cycle?
Acetyl CoA + 3 NAD+ + FAD + GDP + Pi + 2H2O –> 2 CO2 + 3NADH + FADH2 + GTP + 2H+ + CoA
What is the first step of the TCA cycle?
Acetyl CoA + OAA –> citric acid
via citrate synthase
What is the second step of the TCA cycle?
citric acid –> isocitrate
via aconitase
What regulates citrate synthase?
inhibited by ATP and NADH
regulated by [OAA]
What is the third step of the TCA cycle?
isocitrate + NAD+ –> alpha-ketogluterate + CO2 + NADH
via isocitrate dehydrogenase
What is the rate limiting enzyme of the TCA cycle?
isocitrate dehydrogenase (step 3)
What regulates isocitrate dehydrogense?
energy charge
stimulated by ADP (low energy)
inhibited by ATP and NADH (high energy charge)
What is the fourth step in the TCA cycle?
alpha-ketogluterate + NAD+ + CoASH –> succinyl CoA + NADH + H+ + CO2
via alpha-KG dehydrogenase
What is the function of the E1 subunit of alpha-KG dehydrogenase?
decarboxylase (plus cofactor thiamine PP)
decarboxylates alpha-KG to CO2 plus a four-carbon succinyl product
What is the function of the E2 subunit of alpha-KG dehydrogenase?
uses lipoic acid to transfer the four-carbon succinyl product to the CoASH
What is the function of the E3 subunit of alpha-KG dehydrogenase?
uses FAD and NAD to regenerate oxidized lipoic acid for E2
What inhibits the activity of alpha-KG dehydrogenase?
E1: ATP
E2: succinyl CoA
E3: NADH
What is step 5 of the TCA cycle?
succinyl CoA + GDP + Pi –> succinate + CoASH + GTP
via succinyl CoA synthase (thiokinase)
Describe the last three steps of the TCA cycle.
designed to convert succinate to OAA
catalyzed by succinic dehydrogenase (producing FADH2), cumarase, and malate dehydrogenase (producing NADH)
What is the overall yield of ATP from glucose to 6CO2?
Total 32 Glucose --> 2 pyruvate + 2NADH + 2 ATP 2NADH --> mito = 5 ATP 2 pyruvate --> 2 acetyl CoA + 2 NADH 2 NADH = 5 ATP 2 Acetyl CoA = 20 ATP
What regulates the TCA cycle?
respiratory control (oxidation of NADH and FADH2) energy charge (ATP inhibits multiple enzymes in the pathway) concentration and regeneration of OAA
What are anaplerotic reactions?
intermediates of a pathway (most often the TCA cycle) that can be diverted into other pathways or those that replenish the necessary substrates after they have been pulled out
How can OAA be replenished?
pyruvate carboxylase reaction
amino acids catabolized to TCA cycle intermediates
PEPCK reaction
What pathway can Succinyl CoA be diverted to?
heme synthesis
What pathways can OAA be diverted to?
glucose
aspartate
asparagine
pyrimidines
What pathways can citrate be diverted to?
fatty acid synthesis
What pathways can alpha-KG be diverted to?
glutamate
glutamine
proline
