Regulation of Glycolysis C483 Spring 2013

1. Which of these enzymatic reactions is NOT a control point for glycolysis? A. Phosphoglycerate kinase B. Hexokinase C. Phosphofructokinase D. Pyruvate kinase 2.Which of these statements is not true of liver cells? A.They have an isozyme of hexokinase that is insensitive to glucose-6-P. B.They have an isozyme of hexokinase that has a higher Km value than other isozymes. C.They use glucose-6-P to regulate blood sugar and to make ribose5-P. D.Their [glucose] is lower than the concentration of glucose in the blood. 3.Which statement is false concerning regulation of glycolysis? A.Hexokinase is deactivated by glucose-6-P via product inhibition. B.Because cellular [AMP] levels remain constant, PFK-1 is mainly regulated by changes in [ATP]. C.Pyruvate Kinase is activated by [fructose-1,6-bP] in feed-forward activation. D.PFK-1 is inhibited by citrate via feedback inhibition.

Regulation Overview Mammal cells Differences in tissues (liver) Points of regulation – Glucose uptake – 3 irreversible steps Logic of regulation

Glucose Entry into Cells Tissues have unique function Isozymes of glucose transporter, GLUT – Insulin dependent in muscle – Higher [glucose] in liver

Hexokinase First irreversible reaction Linked to glucose uptake – Locks glucose in cell Many isozymes – Most inhibited by glucose- 6-phosphate – Product inhibition Not a committed step

Glucokinase Isozyme in liver Higher Km Not inhibited by glucose-6-P Why? Liver serves to modulate blood sugar

PFK-1 Committed step Regulated by energy charge (ATP, AMP ratio) – [ATP] does not change much Citrate – Feedback inhibition

Pyruvate Kinase Third irreversible step Activated by F1,6bP – Feed-forward activation – Curve becomes hyperbolic

PK in Liver Regulated by glucagon Exercise: based on what you know about glucagon, how does this graph make metabolic sense?

Answers 1.A 2.D 3.B