1. Gluconeogenesis Associate professor Shi-Jie Liu, Ph D. Department of clinical pharmacology, Xinqiao hospital, TMMU.

2. Overview of gluconeogenesis  Gluconeogenesis is the generation of glucose from other substrates. Like many metabolic pathways it happens mostly in the liver, and is triggered by the action of insulin.  Gluconeogenesis begins with various substrates converted into pyruvate.and this proceed though what is essentially the reverse of glycosis(except for a few committed steps).  3 and 4-carbon substrates can enter the gluconeogenesis pathway. Lactate from anaerobic exercise in skeletal muscle is easily converted to pyruvate; this happens as part of the Cori cycle.

3. Overview of gluconeogenesis Oxaloacetate (an intermediate in the citric acid cycle can also be used for gluconeogenesis. Amino acids, after their amino group has been removed, feed into parts of the citric acid cycle, and can thus can generate glucose in this pathway. Fatty acids cannot be turned into glucose, as they are broken down into the two carbon acetyl CoA. (However glycerol which is a part of all triacylglycerides can be used in gluconeogenesis).

4. Amphibolic pathway: a metabolic pathway that functions in both anabolism and catabolism Stage1 Stage2 Stage3

5. Stage1:to invest 2 ATP Stage2:to produce 4 ATP and 2NADH 2 pyruvate + 2ATP + 2NADH + 4H + +2H 2 O =glucose + 2ADP + 2NAD + + 6Pi  G°' = +73.3 kJ/mol 2 pyruvate + 4ATP + 2GTP + 2NADH + 4H + + 6H 2 O =glucose + 4ADP + 2GDP + 2NAD + + 6Pi  G°' = - 47.6 kJ/mol Total: 6 molecules ATP, 2 molecules NADH

6. The special reactions Pyruvate+ CO 2 + H 2 O + ATP= oxaloacetate +ADP+ Pi + 2H + ΔGº’ kJ/mol -2.1 Oxaloacetate+GTP= Phosphoenolpyruvate+ CO 2 +GDP +2.9 Fructose-1,6-bisphosphate+ H 2 O= Fructose- 6-phosphate+ Pi -16.3 Glucose-6-phosphate+ H 2 O=Glucose+ Pi -12.1

14. Fuitle cycle glucose + 2ADP + 2NAD + + 6Pi =2 pyruvate + 2ATP + 2NADH + 4H + + 2H 2 O  G°' = -73.3 kJ/mol 2 pyruvate + 4ATP + 2GTP + 2NADH + 4H + + 6H 2 O = glucose + 4ADP + 2GDP+ 2NAD + +6Pi  G°' = - 47.6 kJ/mol Total:2ATP+2GTP+4H 2 O = 2ADP + 2GDP+6Pi  G°' = -121 kJ/mol Fuitle cycle:a set of opposing reactions that can be arranged in a cycle, but usually do not occur simultaneously; functioning of such reactions in both directions is avoided by metabolic control mechanisms to prevent energy waste.

16. Cori cycle

17. Thanks