1 / 18

Edited by Attila Sandor

The Department of Biochemistry of Medical Faculty. Presents now. Regulation and Pathology of Lipid Metabolism. Edited by Attila Sandor. Regulation and Pathology of L ipid M etabolism The fatty acid-glucose cycle R egu lation of cholesterol synthesis at HMG-CoA reductase the

verna
Télécharger la présentation

Edited by Attila Sandor

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. The Department of Biochemistry of Medical Faculty Presents now Regulation and Pathology of Lipid Metabolism Edited by Attila Sandor

  2. Regulation and Pathology of Lipid Metabolism The fatty acid-glucose cycle Regulation of cholesterol synthesis at HMG-CoA reductasethe inhibitory effect of cholesterol by covalent modification (-P) at the level of gene expression Regulation of ketogenesis at HMG-CoA synthase by succinylation changed gene expression Regulation of fatty acid synthesis at acetyl-CoA carboxylase Pathological lipid metabolism Tay-Sachs disease Propionemia, methylmalonemia Familial hypercholesterolemia Author`s picture

  3. Combined inhibititory effect of ATP and citrate on the PFK activity Reg. in Metab. by Newsholm, 1977

  4. Author`s picture

  5. The theory of glucose/fatty acid cycle The theory of the cycle states, if plasma Glc is decreased, fatty acids are mobilized from adipose tissues (fasting, effect of glucagon) and the increased fatty acid level will decrease Glc utilization, restoring Glc level and maintaining homeostasis in this way. Author`s picture

  6. Regulation and Pathology of Lipid Metabolism The fatty acid-glucose cycle Regulation of cholesterol synthesis at HMG-CoA reductasethe inhibitory effect of cholesterol by covalent modification (-P) at the level of gene expression Regulation of ketogenesis at HMG-CoA synthase by succinylation changed gene expression Regulation of fatty acid synthesis at acetyl-CoA carboxylase Pathological lipid metabolism Tay-Sachs disease Propionemia, methylmalonemia Familial hypercholesterolemia Author`s picture

  7. HMG-CoA is a branchpoint Cholesterol Reductase HMG-CoA synthase Cleavage enzyme Ketone bodies

  8. HMG-CoA reductase is the regulated enzyme on the way to cholesterol synthesis HMG-CoA Phosphorylation by AMPK Cholesterol Insulin Gene Expression Glucagon Drugs (Statins)

  9. AMP dependent Protein Kinase Authors`picture

  10. Regulation and Pathology of Lipid Metabolism The fatty acid-glucose cycle Regulation of cholesterol synthesis at HMG-CoA reductasethe inhibitory effect of cholesterol by covalent modification (-P) at the level of gene expression Regulation of ketogenesis at HMG-CoA synthase by succinylation changed gene expression Regulation of fatty acid synthesis at acetyl-CoA carboxylase Pathological lipid metabolism Tay-Sachs disease Propionemia, methylmalonemia Familial hypercholesterolemia Author`s picture

  11. HMG-CoA synthase is regulatorory for ketone body synthesis

  12. Regulation of ketone body synthesis trough the HMG-CoA synthase Acetoacetyl-CoA Acetyl-CoA HMG-CoA synthase Acetyl-CoA Succinyl-CoA HMG-CoA The liver contains two HMG-CoA synthases, one cytosolic for cholesterol synthesis and an other mitochondrial rate limiting for for ketone body synthesis. The latter undergoes a short term covalent modification via succinylation/desuccinylation of pre-existing enzyme. This presents a rare way of covalent modification of an enzyme.

  13. Regulation and Pathology of Lipid Metabolism The fatty acid-glucose cycle Regulation of cholesterol synthesis at HMG-CoA reductasethe inhibitory effect of cholesterol by covalent modification (-P) at the level of gene expression Regulation of ketogenesis at HMG-CoA synthase by succinylation changed gene expression Regulation of fatty acid synthesis at acetyl-CoA carboxylase Pathological lipid metabolism Tay-Sachs disease Propionemia, methylmalonemia Familial hypercholesterolemia Author`s picture

  14. Regulation of acetyl-CoA carboxylase (ACC) CH3-COSCoA COO-CH3-COSCoA CO2-Biotin ACC acetyl-CoA malonyl-CoA Glucagon Insulin ACC, the 2nd and ATP-citrate lyase, the1st lipogenic enzymes are regulated by an inhibiting phosphorylation Stryer,5th ed. 22.26, p.625

  15. Regulation and Pathology of Lipid Metabolism The fatty acid-glucose cycle Regulation of cholesterol synthesis at HMG-CoA reductasethe inhibitory effect of cholesterol by covalent modification (-P) at the level of gene expression Regulation of ketogenesis at HMG-CoA synthase by succinylation changed gene expression Regulation of fatty acid synthesis at acetyl-CoA carboxylase Pathological lipid metabolism Tay-Sachs disease Propionemia, methylmalonemia Familial hypercholesterolemia Author`s picture

  16. Genetic diseasis in connection to fatty acid oxidation propionemia methylmalonyl-uria member of citric acid cycle Lehn.,4th ed.17-11 p.642

  17. Regulation and Pathology of Lipid Metabolism The fatty acid-glucose cycle Regulation of cholesterol synthesis at HMG-CoA reductasethe inhibitory effect of cholesterol by covalent modification (-P) at the level of gene expression Regulation of ketogenesis at HMG-CoA synthase by succinylation changed gene expression Regulation of fatty acid synthesis at acetyl-CoA carboxylase Pathological lipid metabolism Tay-Sachs disease Propionemia, methylmalonemia Familial hypercholesterolemia Author`s picture

  18. THANK YOU FOR YOUR ATTENTION The honored audience has the opportunity now to download the pictures of this lecture from here or from the intranet: RegPathLipidMetab.ppt Attila Sandor

More Related