9. Acetyl-CoA. AMP citrate and fructose 2, 6-bisphosphate act reciprocally to coordinate both pathways Acetyl-CoA inhibits the pyruvate dehydrogenase complex (of glycolysis), but activates the pyruvate carboxylase (of gluconeogenesis) AMP inhibits fructose 1, 6-bisphosphatase(FBPase 1), but activates phosphofructokinase-1(PFK-1 Citrate inhibits pfK-1 and activates FBPase Fructose-2, 6-bisphosphate(a regulator, not an intermediate) in liver cells, signaling a high blood glucose/glucagon level, activates PFK- F and inhibits FBPase-1
9. Acetyl-CoA, AMP, citrate, and fructose 2,6-bisphosphate act reciprocally to coordinate both pathways • Acetyl-CoA inhibits the pyruvate dehydrogenase complex (of glycolysis), but activates the pyruvate carboxylase (of gluconeogenesis). • AMP inhibits fructose 1,6-bisphosphatase (FBPase- 1), but activates phosphofructokinase-1 (PFK-1). • Citrate inhibits PFK-1 and activates FBPase-1. • Fructose-2,6-bisphosphate (a regulator, not an intermediate) in liver cells, signaling a high blood glucose/glucagon level, activates PFK-1 and inhibits FBPase-1
F-2, 6-bisphosphate is synthesized from(and degraded to) fructose 6-phosphate in a reaction catalyzed by pfK-2(and FBPase-2 PFK-2 and F BPase-2 are two distinct activities of a single, bifunctional protein Glucagon stimulates the phosphorylation of PFK. 2/FBPase-2. which inhibits the PFK-2 activity, but activates the FBPase-2 activity, thus inhibiting the glycol ysis, but stimulating the gluconeogenesis
• F-2,6-bisphosphate is synthesized from (and degraded to) fructose 6-phosphate in a reaction catalyzed by PFK-2 (and FBPase-2). • PFK-2 and FBPase-2 are two distinct activities of a single, bifunctional protein. • Glucagon stimulates the phosphorylation of PFK- 2/FBPase-2, which inhibits the PFK-2 activity, but activates the FBPase-2 activity, thus inhibiting the glycolysis, but stimulating the gluconeogenesis
Glucose The alternative fates or pyruvate are Gluconeogenesis coordinately regulated Oxaloacetate by acetyl-CoA pyruvate carboxylase Pyruvate pyruvate →0 dehydrogenase complex CO Acetyl-CoA Citric acid cycle Energy
The alternative fates of pyruvate are coordinately regulated by acetyl-CoA
Glycolysis Gluconeogenesis Fructose 6-phosphate F-2,6-BP AMP O ⊙F2,6-BP ATPO Phosphofructo Fructose kinase 1, 6-bisphosphatase ⊙AMP Citrate O O Citrate H+O >Fructose 1, 6-bisphosphate Fructose 2,6 bisphosphate (F-2, 6-BP), AMP, and citrate have opposite effect on the enzymatic activities of PFK-1 and FBPase-1
d Fructose 2,6 bisphosphate (F-2,6-BP), AMP, and citrate have opposite effect on the enzymatic activities of PFK-1 and FBPase-1
100 100 80 +F2, 6BP 880 F2.6BP >- 60 60 40 40 20 F2 6BP 一 20 +F2. 6BP 00.050.10.20.40.71.02.040 0 50 100 [Fructose 6-phosphate](mM) [ Fructose 1, 6-bisphosphate](uM) (a) (b) O--P-0-CH2 F-26-BP activates O、CH2OH KH HO/ PFK-1, but inhibits 0→P-0 FBPase-1 OH H O Fructose-2, 6-bisphosphate
F-2,6-BP activates PFK-1, but inhibits FBPase-1