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LIPID METABOLISM
Dr. Vijay Marakala, MBBS, MD.
Assistant professor BIOCHEMISTRY SIMS & RC
LIPID METABOLISM
Catabolism of FA
Oxidation
Anabolism of FA De-novo
synthesis
Ketone body metabolism
Cholesterol metabolism
Lipoprotein metabolism
Triacylglycerol
Fatty acids
Acetyl CoA
TCA
CO2
Diet
Cholesterol
Ketone bodies
Steroids
CH, AA
Overview of lipid metabolism
FATTY ACID METABOLISM» Fatty acids are stored as Triacylglycerol
» Constitute 84% of stored energy+ Protein - 15%+ Carbohydrate (glucose or glycogen) - <1%
» Fatty acids mobilized from Triacylglycerol are oxidized to meet the energy needs of a cell
UTILIZATION OF FATTY ACIDS AS A FUEL3 stages Mobilization of FA
from TG into tissues
Activation and transportation of FA into mitochondria
Degradation of FA by oxidation into
acetyl-CoA
Mobilization of FA from TG into tissues
(Adrenalin, Glucagon, ACTH)
Mobilization of FA from TG
into tissues
Mobilization of FA from TG into
tissues
9FATE OF GLYCEROL
OH
OH
OH
Glycerol
In Liver:
DihydroxyacetonePhosphate
Pyruvate
Glucose
Glycolysis
Gluconeogenesis
OXIDATION OF FATTY ACIDS
» Saturated FA - β-oxidation - Peroxisomal FA oxidation - α-oxidation - ω-oxidation» Unsaturated FA - Modified β-oxidation pathway
β- OXIDATION - DEFINITION
β Oxidation of fatty acid is oxidation of fatty acid at the β carbon atom with successive
removal of two carbon atoms as acetyl CoA
Long assay
β- OXIDATION - STEPS
1• Activation of fatty acids in the cytosol
2• Transport of activated fatty acids in to
mitochondria
3• β-Oxidation proper in the mitochondria
β- OXIDATION- OVERVIEW
ACTIVATION OF FATTY ACIDS
Occurs in outer mitochondrial membrane for long chain fatty acids
Fatty Acid Acyl-CoA
Transport of activated fatty acids in to mitochondria
CAT-I
CAT-II
Overall process of β-oxidation
CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CO-S-CoA16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1
αβω
8-Acetyl-CoA
7 Cycles of β –oxidation withSuccessive removal of 2 carbon units
7NADH+H+
7FADH2
Palmitoyl-CoA
Acetyl-CoA
SEQUENCE OF REACTIONS OF β-OXIDATION
Oxidation by FAD
Hydration
Oxidation by NAD
Thiolysis
oxidation
oxidation
hydration
thiolysis
C16
7 rounds
Acyl-CoA
Trans enoyl-CoA
3-Hydroxy acyl-CoA
3-Ketoacyl-CoA
Acyl-CoA Shortened by 2 carbon atoms
Acetyl-CoA
ENERGETICS OF COMPLETE OXIDATION OF PALMITIC ACID
Oxidation 7 cycles
7 FADH2 x 2ATP/FADH2 14 (10.5)
7 NADH + H+ x 3ATP/NADH 21 (17.5)
From 8 acetyl CoA
Each acetyl CoA provides 12 ATP by TCA cycle 96 (80)
Total ATP produced from one palmitic acid 131 (108)
Total ATP used for activation 2
NET YIELD OF ATP 129 (106)
REGULATION OF β-OXIDATION
AVAILABILITY OF FATTY ACIDS
Hormones GlucagonEpinephrineInsulin
SYNTHESIS OF FATTY ACIDS
Inhibition of carnitine acyl transferase I by malonyl CoA
SIGNIFICANCE OF β OXIDATION
Provision of energy
• 20-30% of energy requirement of the cell
• Major pathway
Ketone bodies
• Diabetes• Starvation
Synthesis of biomolecules from
acetyl CoA
• Acetylcholine • Cholesterol
β-OXIDATION OF ODD CHAIN FATTY ACIDS
Oxidized by β–oxidation in the same way as that of even number, except the propionyl-CoA and acetyl-CoA are the end products
CH3-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CO-S-CoA 11 10 9 8 7 6 5 4 3 2 1
αβ
β-OXIDATION OF ODD CHAIN FATTY ACIDS
β-OXIDATION OF ODD CHAIN
FATTY ACIDS
D
L
β-OXIDATION OF UNSATURATED FATTY ACIDS
• Requires additional enzymes• Isomerase and reductase
Presence of double bonds
β-OXIDATION IN PEROXISOMES
α-OXIDATION
• Minor pathway• Involves oxdn of fatty acids at α carbon atom• One carbon is removed from the carboxyl
end and released as CO2• Occurs in endoplasmic reticulum• Phytanic acid oxidation
α-OXIDATION
ω-OXIDATION
It is a minor pathwayTakes place in microsomes Involves oxidation of last
carbon atom ( ω carbon)More common with
medium chain fatty acids
Impaired Oxidation of Fatty Acids Gives Rise to Diseases Often
Associated With Hypoglycemia
DISORDERS OF FA OXIDATION
Disorders
Carnitine deficiency
Jamaican vomiting sickness
Refsum’s disease
Zellweger’s syndrome
DISORDERS OF FA OXIDATION
Can occur particularly in the newborn—and especially in preterm infants
Carnitine deficiency
Features • Muscle cramps, muscle
weakness
DISORDERS OF FA OXIDATION
• Caused by eating the unripe fruit of the akee tree, which contains a toxin, hypoglycin, that inactivates medium and short chain acyl-CoA dehydrogenase, inhibiting β-oxidation and causing hypoglycemia.
Jamaican vomiting sickness
DISORDERS OF FA OXIDATION
Is a rare neurologic disorder due to a defect that causes the accumulation of phytanic acid, which is found in plant foodstuffs and blocks β-oxidation.
Refsum’s disease
Features • Cerebral ataxia• Periphaeral neuropathy• Retinitis pigmentosa
DISORDERS OF FA OXIDATION
Occurs in individuals with a rare inherited absence of peroxisomes in all tissues.
Zellweger’s syndrome
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