Carbohydrate Regulation* Flashcards
Understand that enzymes that operate _____ from equilibrium (large ____) are rate limiting and good candidates for regulation
Understand that enzymes that operate far from equilibrium (large -∆G) are rate limiting and good candidates for regulation.
Enzymes that operate far from equilibrium are rate limiting and are well suited as control points because modulation of their activity will have a significant effect on flux through a pathway. In contrast, enzymes that operate near equilibrium may be so efficient that a reduction in their activity will have little or no effect on the overall flux.
Hexokinase (1), Phosphofructokinase (3), and Pyruvate Kinase (10) catalyze glycolytic steps that are rate limiting
Understand that in reversing a pathway, an ______ route is required to get around irreversible steps which in the forward direction are highly _______. Such bypasses offer the opportunity for reciprocal regulation of flux in the forward and reverse directions.
Understand that in reversing a pathway, an independent route is required to get around irreversible steps which in the forward direction are highly exergonic. Such bypasses offer the opportunity for reciprocal regulation of flux in the forward and reverse directions.
The same steps that are rate limiting in Glycolysis (Hexokinase, Phosphofructokinase, and Pyruvate Kinase) are the ones that need to be bypassed when going in the direction of Gluconeogenesis
Know examples of regulating glycolysis/gluconeogenesis by allosteric ligands, reversible phosphorylation, and hormonal regulation of gene expression
PFK is allosterically inhibited by ATP as a feedback inhibitor. In contrast, when an allosteric inhibitor binds, the conformation assumed places a destabilizing negative charge (E161) near the negatively charged substrate.
In contrast, AMP effectively competes with ATP for binding at the allosteric site signaling
Glycolysis to speed up to replenish the ATP supply. When an allosteric activator binds, PFK assumes a conformation that places a stabilizing positive charge (R162) near the negatively charged substrate.
F2,6BP also competes with ATP for binding to the allosteric site on PFK, thereby preventing feedback inhibition of Glycolysis.
In contrast, F2,6BP and AMP bind to an allosteric site on FBPase and inhibit, thereby slowing Gluconeogenesis when Glycolysis is active.
The synthesis and breakdown of F2,6P is controlled by a carefully regulated bifunctional enzyme. In the dephosphorylated state, the catalytic site in the kinase domain (PFK-2) is active. In the phosphorylated state, the catalytic site in the phosphatase domain (FBPase-2) is active
Glucagon generally elevates the amount of glucose in the blood by promoting gluconeogenesis (formation of glucose from non-sugars) and glycogenolysis.
Conversely, when blood Glu concentration is high, insulin promotes decreased enzyme phosphorylation resulting in increased F2,6P thereby increasing Glycolysis and inhibiting Gluconeogenesis.
Glucagon = gluconeogenisis
Insulin = glycolysis
Know examples of regulating glycogen synthesis/breakdown by reversible phosphorylation and allosteric ligands
In the pathway that breaks down glycogen, glycogen phosphorylase is the enzyme regulated
When Glucagon/ Epi increases, Glycogen is broken down in liver, and when Insulin increases, Glycogen is synthesized in muscle
An increase in blood Glu results in increased Glu uptake which stimulates Glycogen synthesis
Insulin increases Glu uptake in muscle (and adipocytes) by increasing the number of Glu transporters at the cell surface (does not occur in brain or liver). In muscle, this results in increased Glycogen synthesis. In adipocytes, this results in increased synthesis of triacylglycerols.
Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis. R phosphor active form increases blood sugar via glycogen breakdown & T dephos inactive form increases Glygogen synthesis since ATP is high!
Know examples of regulating the Pyruvate DHase Complex by reversible phosphorylation and product inhibition.
DHase is responsible in transforming pyruvate into acetyl-CoA by a process called pyruvate decarboxylation.
The kinase is inactivating & the phosphatase is activating.
The Kinase is activated by NADH and Acetyl-CoA to phosphorylate and inactivate E1,
whereas pyruvate and ADP inhibit the Kinase
The Phosphatase is activated by calcium ion to convert E1 back to the active form as part of the fight-or-flight response
Know examples of regulating the Citric Acid Cycle by product inhibition and feedback inhibition at catalytic and allosteric sites.
Product Inhibition: Cit Synth by Cit, iCit DHase by NADH, and α-ketoglutarate DHase by NADH and Succ-CoA
Feedback Inhibition: Cit Synth by Succ-CoA
Allosteric: iCit DHase is activated by ADP and inhibited by ATP
Understand the roles of insulin, glucagon and catecholamines in coordinating metabolism in different tissues.
Glucagon = gluconeogenisis
Insulin = glycolysis
When Glucagon/ Epi increases, Glycogen is broken down in liver, and when Insulin increases, Glycogen is synthesized in muscle
Insulin increases Glu uptake in muscle (and adipocytes) by increasing the number of Glu transporters at the cell surface (does not occur in brain or liver). In muscle, this results in increased Glycogen synthesis. In adipocytes, this results in increased synthesis of triacylglycerols.
Understand the effects of insulin and glucagon on key enzymes in carbohydrate metabolism.
see pg. 161
