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Fatty Acid Degradation and Biosynthesis: Department of Biochemistry
Fatty Acid Degradation and Biosynthesis: Department of Biochemistry
Department of Biochemistry
Jeerus Sucharitakul
Fatty acid breakdown
Pi2 + H2O Pi + Pi
CH3
H H2
H3C N+ CH2 C C COO- Carnitine
CH3 OH
β-oxidation
Oxidative phosphorylation
Oxidation of fatty acids
IV Thiolysis
II Hydration
Oxidation of fatty acids
β -oxidation of saturated
fatty acids
β -oxidation of unsaturated
fatty acids
-Most lipid in animals and plants
Are unsaturated fatty acids
-Double bonds are in cis
conformation.
β -oxidation of unsaturated fatty acids
H2 H2 H2
O Monosaturated fatty acids
C C C C C C SCoA
H H
•Double bond at C-3 prevents
β-oxidation reduction the bond between
C-2 and C-3
O
H2
C C C C SCoA •Enzyme enoyl-CoA hydratase
H H
cis-∆3-enoyl CoA
is only specific for substrate-
trans conformation.
Isomerase
•Enzyme isomerase translocate
H O double bond from cis to trans
H2
C C C C SCoA conformation without reduction.
H
trans-∆2-enoyl CoA
β -oxidation of monounsaturated fatty acids
β -oxidation of polyunsaturated fatty acids
β -oxidation of polyunsaturated fatty acids
β -oxidation of fatty acids
β-oxidation
C3
Acetyl CoA Acetyl CoA + Propionyl CoA
Carboxylation
Succinyl CoA
TCA cycle
Conversion of propionyl-CoA into succinyl-CoA
B12 is a cofactor of methylmalonyl-CoA mutase.
Vitamin B12 deficiency
•Serious disease; pernicious anemia
•Vit B12 can not be synthesized by animals or plants
but only few microorganism can do it.
•Vit B12 is synthesized by intestinal bacteria
•Absorption of Vit B12 in intestinal lumen requires a
glycoprotein, intrinsic factor.
Pernicious anemia
-Genetic deficiency disease, for intrinsic factor
-Low production of hemogolbin
-Low production of erythrocytes
-Severe impairment of central nervous system
Animals can not use acetyl CoA for gluconeogenesis.
O O
H2
C C C
-
O S CoA
Malonyl-CoA
Lipid biosynthesis
Acetyl-CoA carboxylase
•Multifunctional enzyme
•Coenzyme; biotin (CO2 carrier)
Lipid biosynthesis
NADPH Acetyl-CoA
Reoxidation of malate
to pyruvate by malate
enzyme
Malonyl CoA
Source of NADPH in cytosol
Cytosolic NADPH is generated by (hepatocyte and adipocyte)
2NADP+ 2NADPH + H+
Malate Pyruvate
Acetyl CoA shuttle
•Acetyl CoA used in fatty acid synthesis is formed in
matrix of mitochondria.
•Inner membrane of mitochondria is impermeable to
acetyl CoA.
•Acetyl CoA is passed into cytosol in form of citrate.
•Citrate is hydrolyzed by enzyme citrate lyase releasing
acetyl-CoA in cytosol
Citrate synthase
Oxaloacetate + Acetyl-CoA Citrate + CoA-SH
Citrate lyase
Citrate + CoA-SH + ATP Oxaloacetate + Acetyl-CoA + ADP + Pi
Acetyl CoA shuttle
Regulation of fatty acid synthesis
Citrate
Acetyl-CoA
Acetyl-CoA Glucagon
carboxylase Epinephrine
Malonyl-CoA
Palmitoyl-CoA
Long chain fatty acid synthesis
Arachidonic acid
Cycloxygenase Lipoxygenase
I Prostaglandins; Leukotrienes;
-pain, inflammation, fever, -Contraction of smooth
wake-sleep cycle muscle in lung
II Thromboxanes; -Allergic reaction or
-vasoconstriction hypersensitivity
-blood clotting
-platelet aggregration
Ecosanoids (C20) are biological signaling in cells.
•Glycerol 3-phosphate is a
precursors for biosynthesis of
triacylglycerols.
•Reactions is catalyzed by two
pathways using enzyme
glycerol 3-phosphate
dehydrogenase for reduction
and glycerol kinase.
Biosynthesis of triacylglycerols
Fatty acyl-CoA
•27-carbon compound
•Component of cellular membranes
•Precursor for steroid hormones
•Precursor for bile acid
•One of risk factors for cardiovascular diseases
CH3
H2C C CH CH2
Isoprene unit
Biosynthesis of cholesterol and steroids
HO OH HO OH
Glycolate Taurocholate
7-dehydrocholesterol
UV light
Dihydroxycholecalciferol
(reactive compound)