The Department of Biochemistry
of Medical Faculty
Presents now
Regulation and Pathology of Lipid
Metabolism
Edited by Attila Sandor
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
Combined inhibititory effect
of ATP and citrate on the PFK activity
Reg. in Metab. by Newsholm, 1977
Author`s picture
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
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 is a branchpoint
Cholesterol
HMG-CoA synthase
Ketone bodies
HMG-CoA reductase is the regulated enzyme
on the way to cholesterol synthesis
HMG-CoA
Phosphorylation by AMPK
Cholesterol
Gene
Expression
Insulin
Glucagon
Drugs (Statins)
AMP dependent Protein Kinase
Authors`picture
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
HMG-CoA synthase
Succinyl-CoA
Acetyl-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.
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
Regulation of acetyl-CoA carboxylase (ACC)
CH3-COSCoA
acetyl-CoA
ACC
CO2-Biotin
COO-CH3-COSCoA
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
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
Genetic diseasis in connection to fatty acid oxidation
propionemia
methylmalonyl-uria
member of citric
acid cycle
Lehn.,4th ed.17-11 p.642
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
THANK YOU FOR YOUR ATTENTION
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Attila Sandor