Lecture 20 Flashcards
CAC- overview
- Hub of cellular metabolism.
- The net reaction of the citric acid cycle is:
Acetyl CoA + 3NAD+ + FAD + GDP + Pi + 2H2O —>
2CO2 + 3NADH + FADH2 + GTP + 2H+ + CoA - Regulation occurs at steps with largest free energy drop
- The two carbons from Acetyl CoA are fully oxidized to CO
- Citric Acid Cycle intermediates are precursors for other metabolites
- 4 pairs of electrons are transferred to oxidize Acetyl CoA to CO2.
- Shuttles transfer reducing power from to the cytosol to the mitochondrial matrix
what type of phosphorylation is succinyl-CoA
substrate-level phosphorylation
Substrate-level phosphorylation
is a type of chemical reaction in which ATP is formed by the direct transfer of a phosphate group to ADP from a substrate or reactive intermediate.
Succinate dehydrogenase
The only enzyme in this pathway that is membrane associated
citrate synthase ΔGº & ΔG
-31.5
negative
Isocitrate dehydrogenase ΔGº & ΔG
-21
negative
α- ketoglutarate dehydrogenase ΔGº & ΔG
-33
negative
malate dehydrogenase ΔGº & ΔG
+29.7
~0
Regulation of the Citric Acid Cycle
• Citrate synthase
– Inhibited by citrate, NADH, succinyl CoA, ATP
– Activated by ADP
• Isocitrate dehydrogenase:
– Inhibited by: ATP
– Activated by: Ca2+ ADP
• α-ketoglutarate dehydrogenase
– Inhibited by succinyl CoA, NADH
– Activated by Ca2+
Substrate availability; product inhibition; competitive feedback inhibition; Allosteric regulation
Why is the citric acid cycle so effective at extracting energy from Acetyl CoA?
Because the two carbons from Acetyl CoA are fully oxidized to CO2
Calculate the oxidation numbers of the two carbons of acetyl CoA (from the acetyl group) before and after they have gone through the citric acid cycle.
Also notice that carbon atoms of 2CO2 generated in one round are not directly from the acetyl group that entered in the same round.
Cataplerotic
depletes intermediates
Anaplerotic
builds up intermediates
How many NADH made in mitochondria?
how many in cytosol?
8
2
glycerophosphate shuttle
is a mechanism that regenerates NAD+ from NADH, a by-product of glycolysis. Its importance in transporting reducing equivalents is secondary to the malate-aspartate shuttle.
The malate-aspartate shuttle
This shuttle is particularly important in heart and liver. It is a shuttle for NADH that does NOT cost ATP. The malate dehydrogenase (MDH) occurs as separate enzymes in mitochondria and cytosol (cMDH & mMDH).