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Regulation of Glycolysis and Gluconeogenesis in Biochemistry 440, Fall 2008 - Prof. Rachel, Study notes of Biochemistry

University of Washington (UW) - SeattleBiochemistry
Prof. Rachel Klevit

This document from biochemistry 440, fall 2008 lecture 19 discusses the regulation of glycolysis and gluconeogenesis through steady state and flux, allosteric regulation, covalent post-translational modifications, and specific enzymes such as phosphofructokinase (pfk-1), hexokinase, and pyruvate kinase. The document also covers the effects of fructose metabolism and the regulation of fructose 2,6 bisphosphate (f2,6bp) and pyruvate kinase and pyruvate carboxylase.

Typology: Study notes

Pre 2010

Uploaded on 03/18/2009

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Biochemistry 440, Fall, 2008 Lecture 19
1
Regulation of Glycolysis
and Gluconeogenesis
Reading assignment:
Chapter 15.3 p. 582 -590 (591-594 optional)
2
Lecture 19
Steady state and Flux
Consider the reaction
A ---> I ---> P
When v1 = v2, then [I] is constant
If v1 = v2 >> 0, then flux is fast
If v1 = v2 > 0, then flux is slow
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Regulation of Glycolysis

and Gluconeogenesis

Reading assignment: Chapter 15.3 p. 582 -590 (591-594 optional) Lecture (^192)

Steady state and Flux

 Consider the reaction

 A ---> I ---> P

 When v 1 = v 2 , then [I] is constant

 If v 1 = v 2 >> 0, then flux is fast

 If v 1 = v 2 > 0, then flux is slow

Lecture (^193)

How is flux regulated?

 Change in substrate concentration [S]

  • most physiological reactions: [S] << Km =>
  • BUT: physiological [S] only vary about 2-fold => =>  Regulation of enzymes Lecture (^194)

Ways to regulate enzymes

Lecture (^197)

Covalent post-translational

modifications

Phosphorylation

Inactive enzyme (^) P-Active enzyme ATPATP ADPADP PPii

Glycolysis and

gluconeogenesis

Fig. 14-

Lecture (^199)

Regulation of Glycolysis:

Phosphofructokinase (PFK-1)

Phosphofructokinase

 Inhibited by ATP, citrate  Activated by ADP, AMP, Fructose 2,6bisP Lecture (^1910)

PFK-1 activity vs. [F6P]

The curves represent the activity of phospho- fructokinase (PFK-1) under two conditions.  Low [ATP]  High [ATP]

Lecture (^1913)

Regulation of PFK-1 and FBPase-

Glycolysis Gluconeogenesis Phosphofructokinase (PFK-1) Fructose 1,6- Bisphosphatase (FBPase) Fructose 6-phosphate Fructose 1,6-bisphosphate +F2,6BP +AMP +ADP

  • ATP
  • citrate
    • AMP
    • F2,6BP
  • Figure 15.16 Figure 15-

Lecture (^1919)

Regulation of Pyruvate kinase and

Pyruvate carboxylase

Glycolysis (^) Gluconeogenesis phosphoenolpyruvate pyruvate oxaloacetate Pyruvate kinase Pyruvate carboxylase PEP carboxy kinase

  • ATP
  • acetylCoA
  • long chain fatty acid
  • alanine
  • F 1,6BP Lecture (^1920)

Regulation of

Gluconeogenesis and Glycolysis

 What would be the metabolic effect of

increased levels of acetyl CoA?