1 / 9

Lecture 10

Lecture 10. Glucose Disposal: Liver and Molecular Mechanisms. Hexose Metabolism. P. hexokinase. Using UTP Releases PP PP hydrolysis pulls reaction to completion. P. Using ATP. glucose. glucose 1-phosphate. glucose 6-phosphate. P. P. P. U. UDP glucose. fructose 6-phosphate.

rowdy
Download Presentation

Lecture 10

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lecture 10 Glucose Disposal: Liver and Molecular Mechanisms

  2. Hexose Metabolism P hexokinase Using UTP Releases PP PP hydrolysis pulls reaction to completion P Using ATP glucose glucose 1-phosphate glucose 6-phosphate P P P U UDP glucose fructose 6-phosphate “Activated Glucose” P P PFK Pyrophosphate hydrolyses to two phosphates Pulls UDP-glucose conversion over fructose 1,6-bisphosphate

  3. Splitting F16BP Triose phosphate Isomerase P P aldolase CH2OP CH2OP CHOH C=O fructose 1,6-bisphosphate CHO CH2OH Glyceraldehyde 3- phosphate Dihydroxyactone phosphate Rest of Glycolysis to pyruvate Involves oxidation of G3P and generation of ATP

  4. Glycogen Synthesis P P Glycogen U UDP glucose P P Glycogen with one more glucose U Note synthesis is C1 C4 C1 end of glycogen attached to glycogenin UDP UDP needs to be made back into UTP Use ATP for this UDP + ATP  UTP + ADP

  5. Liver Glucose Uptake • GLUT-2 used to take up glucose from bloodstream • Very high activity and very abundant • [Glucose] blood = [Glucose] liver • Glucokinase • Rapidly converts GG6P • Not inhibited by build up of G6P • High Km (10 mM) for glucose – not saturated by high levels of liver glucose • So [G6P] rapidly increases as blood [glucose] rises • G6P can stimulate inactive GS • Even phosphorylated GS • Glucose itself also stimulates the dephosphorylation of GS • Via a slightly complex process that involves other kinases and phosphatases which we needn’t go into right now 

  6. Glycogenesis • In liver • The “push” mechanism • Glycogenesis responds to blood glucose without the need of insulin • Although insulin WILL stimulate glycogenesis further • In muscle • [G6P] never gets high enough to stimulate GS • “Push” method doesn’t happen in muscle • More of a “pull’ as insulin stimulates GS • In both cases • 2 ATPs required for the incorporation of a glucose into glycogen chain • GG6P and UDPUTP • Branching enzyme needed to introduce a16 branch points • Transfers a segment from one chain to another • Limit to the size of glycogen molecule • Branches become too crowded, even if they become progressively shorter • Glycogen synthase may need to interact with glycogenin to be fully active

  7. A Tale of Two Kinases • Glucokinase (GK) • Only works on glucose • High Km for glucose (~10mM) • Not inhibited by G6P • Only presents in liver, beta-cells • Responsive to changes in [glucose] blood • Hexokinase (HK) • Works on any 6C sugar • Km for glucose ~0.1mM • Strongly inhibited by its product G6P • Present in all other tissues • If G6P is not used immediately, its build up and inhibits hexokinase • Easily saturated with glucose

  8. Fructose Metabolism Glyceraldehyde 3-phosphate Glyceraldehyde fructokinase P CH2OH CH2OP Aldolase B CHOH CHOH fructose Using ATP Triose Kinase fructose 1-phosphate CHO CHO hexokinase CH2OP P C=O CH2OH fructose 6-phosphate Dihydroxyactone phosphate PFK ‘normal glycolysis’ ‘normal glycolysis’

  9. Fructose Metabolism • Fructose entry into cells does not require insulin • In muscle, fructose just enters glycolysis • Or could be made into glycogen if insulin stimulus available! • F6P  G6P  G1P  UDP-glucose  Glycogen • In liver, fructokinase traps fructose • FK produces F1P • FK is quite fast in comparison to the aldolase B that uses the F1P • F1P can build up • But more seriously producing ‘dead’ F1P traps phoshpate • FK reaction consumes ATP • Lack of phosphate akes new ATP synthesis difficult • ATP levels in liver fall • Even more serious in people with a deficiency in Aldolase B

More Related