Post on 02-Feb-2016
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Edited by Attila Sandor
The Department of Biochemistryof Medical Faculty
Presents now
Regulation and Pathology of Lipid Metabolism
Regulation and Pathology of Lipid Metabolism
The fatty acid-glucose cycle
Regulation of cholesterol synthesis at HMG-CoA reductase the 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
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Combined inhibititory effect of ATP and citrate on the PFK activity
Reg. in Metab. by Newsholm, 1977
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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.
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Regulation and Pathology of Lipid Metabolism
The fatty acid-glucose cycle
Regulation of cholesterol synthesis at HMG-CoA reductase the 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
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HMG-CoA is a branchpoint
Cleavage enzyme
Reductase
HMG-CoA synthase
Ketone bodies
Cholesterol
HMG-CoA reductase is the regulated enzyme on the way to cholesterol synthesis
Phosphorylation by AMPK
Drugs (Statins)
Cholesterol
Insulin
Glucagon
HMG-CoA
GeneExpression
AMP dependent Protein Kinase
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Regulation and Pathology of Lipid Metabolism
The fatty acid-glucose cycle
Regulation of cholesterol synthesis at HMG-CoA reductase the 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
HMG-CoA synthase is regulatorory for ketone body synthesis
Regulation of ketone body synthesis trough the HMG-CoA synthase
Acetoacetyl-CoA
Acetyl-CoA
Acetyl-CoA
HMG-CoA
HMG-CoA synthase
Succinyl-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.
Regulation and Pathology of Lipid Metabolism
The fatty acid-glucose cycle
Regulation of cholesterol synthesis at HMG-CoA reductase the 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
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Regulation of acetyl-CoA carboxylase (ACC)
COO-CH3-COSCoAACC CO2-Biotin
CH3-COSCoA
acetyl-CoA malonyl-CoA
ACC, the 2nd and ATP-citrate lyase, the1st lipogenicenzymes are regulated by an inhibiting phosphorylation
Stryer,5th ed. 22.26, p.625
Insulin Glucagon
Regulation and Pathology of Lipid Metabolism
The fatty acid-glucose cycle
Regulation of cholesterol synthesis at HMG-CoA reductase the 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
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member of citric acid cycle
Lehn.,4th ed.17-11 p.642
Genetic diseasis in connection to fatty acid oxidation
propionemia
methylmalonyl-uria
Regulation and Pathology of Lipid Metabolism
The fatty acid-glucose cycle
Regulation of cholesterol synthesis at HMG-CoA reductase the 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
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Attila Sandor
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