Download Citric Acid Cycle Regulation

Citric Acid Cycle Regulation
Pyruvate
Inhibited by NADH, ATP
1
and acetyl CoA
Acetyl CoA
2 Inhibited by ATP
Oxaloacetate
Citrate
Malate
Fumarate
Isocitrate
3
Inhibited by ATP, NADH
Stimulated by ADP
α-Ketoglutarate
Succinate
4
Succinyl CoA
Inhibited by Succinyl CoA,
NADH and ATP
ATPase
Figures from:
http://www.nobel.se/chemistry/laureates/1997/press.html
Electron Transport and Oxidative Phosphorylation
H+
H
+
2H +
H
H+
+
H+
H+
H+
H+
H+
H
H+
H
2H+
H+
+
H+
+
H+
2H+
2H+
Inter-membrane space
III cyto
IV
C
B
C
A
CoQ
I
2e-
NADH
Matrix
2e -
2e -
II
2e ATP
Synthase
NAD + FADH FAD
2
2H+ + 1/2 O 2 + 2e-
H2O
ADP + Pi ATP
Fate of Pyruvate (anaerobic)
If no Oxygen around, cant enter Citric Acid Cycle (CAC).
Can only do glycolysis.
Each round of glycolysis produces a net gain of 2 ATPs.
Better than nothing so use glycolysis.
But supply of NAD+ is limited in cytoplasm so must
regenerate it to allow glycolysis to continue!
Step 5 of glycolysis converts NAD+ to NADH (G3P to G1,3BP)
For next round of glycolysis to occur need NADH converted
to NAD+ for use in step 5.
How cells (muscle especially) accomplish this?
Pyruvate (Py), the end product of glycolysis, is converted to
lactate. At the same time NADH is converted to NAD+.
This regenerates NAD+ for use in glycolysis.
lactate
pyruvate
NAD+
G3P
NADH
G1,3BP
Lactate is then shipped out of muscle, into blood stream to
liver. When reaches liver,
Lactate (muscle) Lactate (liver)
Py
Glucose
Muscle
Phosphofructokinase Regulation
Enough ATP in Cell
ATP
P
ATP binds to effector site
- turns PFK off
- no glycolysis
- no more ATP made
Low ATP in Cell
ATP
AMP
AMP
P
P
P
ADP
AMP binds to effector site
- turns PFK on
- glycolysis proceeds
- ATP made
In Liver
enzyme PFK-2 makes fructose 2,6 bisphosphate (F2,6BP) only
when enough glucose in cell.
F2,6BP binds to PFK-1 and turns it on so glycolysis will
occur
Insulin turns PFK-2 on thereby starting glycolysis
Glucagon turns PFK-2 off thereby stopping glycolysis