Enzymes & metabolism Flashcards
What happens when glucagon binds to a GPCR?
The G-protein subunit is activated (binds GTP) and in turn, activates adenylyl cyclase. Adenylyl cyclase will start converting ATP to cAMP. cAMP binds to PKA and subunits dissociates and are thus activated. PKA phosphorylates the protein with PFK-2 activity, causing FBPase-2 activity instead. This lowers levels of fructose 2,6-biphosphate in the cell. Fructose 2,6-biphosphate is a strong activator of PFK-1, which is the enzyme that does the reaction that brings fructose-6-phosphate into glycolysis. When f2,6BP levels are low, PFK-1 activity is very low and glycolysis is thus inhibited (Glucagon = we don’t want to break down glucose)
What happens when insulin binds to GPCR?
Inhibits FBPase-2 activity promoting PFK-2 activity -> more F26BP -> higher PFK-1 activity -> fructose-6-phosphate into glycolysis
Whats needed for glycolysis?
NAD+, ATP, glucose
ATP-dependent/generating steps in glycolysis
Glucose -hexokinase-> glucose 6-phosphate
Fructose 6-phosphate -PFK-1->fructose 1,6-biphosphate
1,3-biphosphoglycerate -phosphoglycerate kinase->3-phosphoglycerate
Phosphoenolpyruvate -pyruvate kinase->pyruvate
Phosphofructokinase-1 (PFK-1)
Important regulatory step for entering glycolysis. Regulated allosterically by fructose 2,6-biphosphate, inhibited allosterically by high levels of ATP. Citrate and PEP also inhibits
Substrate level phosphorylation
Soluble enzymes and chemical intermediates phosphorylate something instead of membrane bound chemicals / transmembrane gradient
Phosphoenolpyruvate (PEP)
Pyruvate kinase will remove phosphor group from PEP to form pyruvate.
Pyruvate kinase
Catalyzes the last step of glycolysis. Inhibited allosterically by high levels of ATP, acetyl-CoA. In liver, cAMP can phosphorylate and inactivate it
Which enzyme breaks down glycogen?
Glycogen phosphorylase
Important enzymes in gluconeogenesis
Pyruvate carboxylase, PEP carboxylase, FBPase-1, glucose 6-phosphotase
Regulation of gluconeogenesis
Pyruvate carboxylase requires acetyl-CoA as positive effector. AMP strongly inhibits FBPase-1
Molecules needed for gluconeogenesis
4 ATP, 2 GTP, 2 NADH, pyruvate/acetyl-CoA
PFK-2/FBPase-2
Protein with dual enzymatic activity depending on PKA activation/inactivation (not phosphorylated; PFK-2 -> formation of fructose 2,6-biphosphate) (phosphorylated; FBPase-2 -> breakdown of F26BP to F6P)
Phosphorylase b kinase
activation of glucogen phosphorylase (b -> a) by phosphorylating 2 places. Activated by glucagon in liver and [AMP] in muscle
PP1 (phosphorylase a phosphotase)
Inactivation of glucagon phosphotase by removal of phosphate groups. Activated by insulin
Glucogen activation cascade
Epinephirne or glucagon binds to CPCR. G-protein activates adenylyl cylase, leading to rise in cAMP. cAMP activates PKA, which activates phosphorylase b kinase, which activated glycogen phosphorylase (b->a). This starts the breakdown of glycogen to glucose 1-phosphate