1. Application of Carbohydrate Metabolism
Review of Allosteric sites
Futile Cycling
Insulin and Glucagon
Amino Sugars

2. Lactate Lactate Lactate Lactate Glucose Glucose Glucose Glucose J = 0
VF > VR
VF < VR
Rate-controlling
Step
Rate-controlling
Step
Rate-controlling
Step
Rate-controlling
Step
Lactate
Lactate
Lactate
Lactate

3. Adenylate kinase
Rule: the balance of ATP, ADP, and AMP in a cell is controlled by adenylate kinase. Reactions that elevate ADP elevate AMP, a major allosteric regulator.
Equation
K =
[ATP][AMP]
[ADP]2
2ADP
ATP +
AMP
Biological Reality
100
ATP 10 2
ADP
AMP
Rule:
A small change in ATP will have a strongly magnifying effect on ADP or AMP concentrations in the cell

4. ATP ATP Examples in Working Muscle ADP K = [ATP][AMP] [ADP]2 ADP 100
0.1 mM
1 mM
0.02 mM
If ATP concentration drops by 10%, adenylate kinase will readjust the levels of ADP and AMP to compensate
100%
-10%
>400%
ATP
ADP
AMP
0.2 mM
0.9 mM
~0.1 mM

5. Key ALLOSTERIC Regulatory Points
GLYCOLYSIS-GLUCONEOGENESIS
Glucose
G6P HK
G6Ptase
-Citrate
F6P
FBP
PFK-1
F6BPtase
-ATP
+AMP
+F2,6P
-AMP
-F2,6P
PEP
PYR PK
-Alanine
+F1,6BP
PYR
OAA PC
+Acetyl-CoA
OAA
PEP
PEPCK
+Glucagon,
cAMP
F6P
F2,6P
PFK-2
FBPase-2
-Citrate
+AMP
-F6P
-ATP
No Allostery

6. Fructose-2,6-Bisphosphate
A Major Allosteric Regulator
Synthesized by Phosphofructokinase-2
Destroyed by Fructose-2,6-Bisphosphatase
Powerful Activator of Glycolysis
Powerful Inhibitor of Gluconeogenesis
Not an Intermediate in any Pathway

7. O O O3POCH2 OH Fructose-6-P Fructose-1,6BP PO3= CH2OH 6 2 OH CH2OH
-D-Fructose-2,6BP 1

8. Fructose 2,6 Bisphosphate
STIMULATES GLYCOLYSIS
INHIBITS GLUCONEOGENESIS

9. Fructose-2,6-bisPO4 (F2,6BP)
the most important allosteric effector that
regulates glycolysis-gluconeogenesis
Activates PFK-1 Inhibits F1,6-bisPtase
F2,6BP level controlled by rates of synthesis and degradation
F6P
F2,6BP
PFK-2
Both in Same Protein
FBPtase-2
F6P
F2,6BP
(-)Citrate
(-)F6P
(+)AMP
(+)Glycerol-3-PO4
PFK-2
FBP-2
(+)F6P
Glycolysis
Gluconeogenesis

10. Hormonal Control of F2,6BP
See P. 458
Hormonal Control of F2,6BP
Glucagon
Epinephrine
Liver
cAPK
cAMP
PFK2 (a)
PFK2 (b)
FBPase2 (b)
FBPase2 (a)
ATP
ADP P
cAPK
Kinase
Phosphatase
Inhibits glycolysis
Stimulates
gluconeogenesis
cAMP
IN LIVER: cAMP activates the phosphatase that destroys F2,6BP
and inhibits the kinase that makes F2,6BP. The combined effect is
to stimulate gluconeogenesis in liver.

11. FUTILE CYCLING F6P PO4 H20 ATP ADP F1,6BP
At steady-state, net reaction is:
ATP + H2O
ADP + PO4
TAKE HOME: To prevent futile cycling, rates of
synthesis and degradation in an ATP-dependent step
must not be the same.

12. INSULIN VS GLUCAGON See Page 686 in Textbook
Insulin: Stimulates Glycolysis, Glycogen Synthesis
Insulin is designed to remove blood glucose and
allow cells to metabolized the glucose or make glycogen
Insulin inhibits gluconeogenesis
Glucagon: Promotes Gluconeogenesis, Glycogen Breakdown
Glucagon is designed to raise blood glucose and
assist liver in controlling blood glucose levels
Elevates cAMP in liver and stimulates protein
phosphorylation
Targets: PEPCK
Glycogen Synthase
FBPtase-2 PK
Glycogen Phosphorylase

13. Amino Sugars Synthesized from D-fructose
Amine group donated by glutamine
Acetylated
Found in GAGS, proteoglycans and glycoproteins
Examples are N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid (Sialic acid)

14. Amidotransferase AMINO SUGARS 2nd C CH2OH C=O HO-C CH2OP C-OH F-6-P
COO-
C-H
CH2
C-NH2
L-Glutamine
H3N- O
CHO
C-NH3
HO-C
CH2OP
C-OH H- +
D-Glucosamine
CHO
C-N
HO-C
CH2OP
C-OH H-
Amidotransferase
-C-CH3 O
Acetyl-CoA
N-Acetyl-D-glucosamine

15. 3-Stages of Glycoprotein Synthesis
Assembly of oligosaccharide
chains on Dolichol
Assembly of polypeptide
chain with Asn-X-Ser/Thr
on ribosomes
Final tailoring of
oligosaccharide
chains in Golgi
Finished product for secretion
or intracellular targeting

16. Energy in Glucose (Aerobic)
Glucose F1,6BP: ATP
F1,6BP 2 Pyr: ATP
2 NADH ATP
Mitochondria
2Pyr 2Acetyl-CoA: 2NADH = 6 ATP
2Acetyl-CoA 4CO ATP
38 ATP
C6H12O O2 6CO H2O Go’= -2,850 kJ/mol
Conserved = 38 ATP x 30.5 kJ/ATP = 1,159 kJ
Efficiency = 40.7%

17. Energy in Succinate Succinate Fumarate: 1 FADH2 = 2 ATP
Fumarate Malate: 0
Malate OAA: 1 NADH = 3 ATP
OAA 4CO2: 2 cycles = 24 ATP
Total = 29 ATP

18. Succinate C4H6O4 3½ O2 4CO2 + 3H2O + Glucose C6H12O6 + 6O2 6CO2 + 6H2O
COOH
CH2 +
3½ O2 4CO H2O
C4H6O4
Glucose
CHO
CH2OH
HO-C-H
H-C-OH
C6H12O O2 6CO H2O