Waxes
simple or complex lipids
Simple
Precursor lipid composed of long chains of Carboxylic acids
Fatty acids
Palmitic acid
Saturated or unsaturated FA
Saturated. 16C:0 double bond
Predominant FA found in COCONUT oil and give its structure
Lauric acid. 12:0
End product of mammalian FA synthesis
Palmitic acid. 16:0
Predominant FA in olive oil
Oleic acid. 18:1 (9)
Essential fatty acid with 2 double bonds at position 9 and 12
Linoleic acid 18:2 (9, 12)
Essential fatty acid with 3 double bonds at position 9, 12 and 15
Linolenic acid 18:3 (9,12,15)
Prostaglandin precursor FA derived from Linoleic acid
Arachidonic acid 20:4 (5, 8, 11, 14)
Also known as OMEGA-6 FA
Linoleic acid
Also known as OMEGA-3 FA
Linolenic acid
FA solid at room temperature
Saturated FA
By-product of of saturation of FA during hydrogenation
Trans fatty acid
Enzyme responsible for activation of FA
Acyl-CoA synthetase
Activation of FA occurs in
cytosol or mitochondria or both
Cytosol
Immediate substrate of Lipogenesis
Acetyl CoA
Common end product of Lipogenesis
Palmitoyl CoA
Rate limiting step and enzyme of Lipogenesis
Acetyl CoA + HCO3 + ATP → Malonyl CoA
Acetyl CoA Carboxylase
Acetyl CoA from mitochondria is transported to the cytosol using _______ shuttle.
Citrate shuttle
Coenzyme used in conversion of Acetyl CoA to Malonyl CoA
Biotin.
Acetyl CoA Carboxylase
How many carbons present in Malonyl CoA
3 carbons
Sequence of steps in elongation of fatty acid
Condesation → Reduction → Dehydration → Reduction
ConReDRed
Primer used in Palmitoyl CoA synthesis
Acetyl CoA
Required donor of reducing equivalents in reduction reactions in FA synthesis
(1) NADPH per reduction reaction = (2) NADPH per cycle
How many NADPH is used up per elongation of acetyl coA to Palmitoyl CoA?
14 NADPH
3 Sources of NADPH
Pentose Phosphate Pathway or HMP shunt
Malic enzyme
Isocitrate Dehydrogenase
Further elongation and desaturation of FA occurs in what part of the cell?
Smooth endoplasmic reticulum
Storage form of fatty acids
Triacylglycerol (TAG)
What substrate needs two Acyl CoA to form TAG?
Glycerol-3-Phosphate
2 Sources of Glycerol-3-Phosphate
- DHAP
2. Phosphorylation of free glycerol
TAG is hydrolyzed to release FA using what enzyme?
Hormone Sensitive Lipase
By-products of TAG hydrolysis
Glycerol and 3 FA
Carbon position in TAG breakdown
Carbon 1 and Carbon 3
Removal of Acetyl CoA fragments from ends of FA
Beta-Oxidation (Lipolysis)
Beta oxidation occurs in what part of the cell?
Mitochondria
Substrate of Beta Oxidation
Palmitate
End products of Palmitate beta oxidation
(8) Acetyl CoA
(7) NADH
(7) FADH2
Rate limiting step and enzyme in Beta Oxidation
Translocation of FA from the cytosol to mitochondria.
Carnitine-palmitoyl transferase
Enzyme that activates FA for transport of Acyl CoA to mitochondria
Fatty Acyl Synthetase
Enzyme that attaches FA to carnitine in the outer mitochondrial membrane
Carnitine AcylTransferase - 1
Enzyme that transfer FA back to CoA in the mitochondrial matrix
Carnitine AcylTransferase - 2
Steps in degradation of fatty acyl coA
Oxidation → Hydration → Oxidation → Thiolysis
OHOT
Chain length specific enzyme used in degradation of Fatty Acyl CoA
Fatty Acyl CoA dehydrogenase
Gross ATP yield in degradation of Palmitate
108 ATPs.
(8) Acetyl CoA (10 ATPs ea) = 80
(7) NADH (2.5 ATP ea) = 17.5
(7) FADH2 (1.5 ATP ea) = 10.5
Net ATP yield in degradation of Palmitate
106 ATPs.
(8) Acetyl CoA (10 ATPs ea) = 80
(7) NADH (2.5 ATP ea) = 17.5
(7) FADH2 (1.5 ATP ea) = 10.5
Activation uses 2 ATP
Product of odd number FA
Propionyl CoA
(2) Sequential enzymes used in oxidation of FA with an odd number of carbons
Propionyl CoA carboxylase
Methylmalonyl CoA mutase
Coenzyme of Methylmalonyl CoA
Vitamin B12
Used in oxidation of very long chain FA (C20, C22)
Peroxisomes
What additional enzyme is required for oxidation of unsaturated very long chain FA?
3, 2 enoyl-CoA isomerase
Inhibitor of Lipogenesis
Long chain fatty acyl CoA
Glucagon
Catecholamines
Inhibitor of Beta oxidation
Malonyl CoA
Insulin
General characteristic of Essential fatty acid deficiency
Ichthyosis (scaly dermatitis) Hair loss Poor wound healing Visual abnormalities Neurologic abnormalities
Preterm infant presents with scaly dermatitis, occasional hypotonia and hypoglycemia.
A. Carnitine Deficiency
B. CPT I deficiency
C. CPT II deficiency
D. MCAD deficiency
Carnitine Deficiency
Generally mild in presentation
A 70/m with severe infection, ichthyosis and impaired wound healing presents with myoglobinuria
A. Carnitine Deficiency
B. CPT I deficiency
C. CPT II deficiency
D. MCAD deficiency
CPT II Deficiency
Affects primarily cardiac and skeletal muscle
Generalities of EFA deficiency + coma/death
A. Carnitine Deficiency
B. CPT I deficiency
C. CPT II deficiency
D. MCAD deficiency
CPT I deficiency
Toxic looking!
Most common inborn error of FA oxidation associated with Sudden infant death syndrome
Medium chain fatty acyl coA dehydrogenase (MCAD) deficiency
Toxin in Jamaican vomiting sickness
Hypoglycin
from unripe fruit of Akee tree
Enzyme deficient in Refsum disease that leads to accumulation of phytanic acid.
A. Phytanoyl-CoA dehydrogenase
B. Phytanoyl-CoA carboxylase
C. Phytanoyl-CoA hydroxylase
D. Phytanoyl-CoA reductase
Phytanoyl-CoA hydroxylase
Child presents with hypertelorism, icthyosis, hepatomegaly, renal cyst, and frontal bossing.
Most probable Dx and enzyme deficient?
Zellweger syndrome (Cerebrohepatorenal syndrome)
Absence of Peroxisomes, marked accumulation of VLCFA in LIVER and CNS
Child undergone appendectomy suddenly presents with progressive ataxia, increased DTR, neurodegenerative changes, darkening of the skin and hypotension?
Most probable Dx and pathology?
Adrenoleukodystrophy (ALD)
Inability to transport VLCFAs, Marked accumulation in CNS, ADRENALS and GONADS.
Neurodegeneration
Adrenocortical insufficency
Hypogonadism
Substrate of Ketogenesis
Acetyl CoA
End products of Ketogenesis
Acetoacetate
Beta-hydroxybutyrate
Acetone
Rate limiting step and enzyme in Ketogenesis
Acetoacetyl CoA + Acetyl CoA → HMG CoA
HMG CoA Synthase
kHetoneS
Ketogenesis occurs in?
Liver mitochondria
Ketolysis occurs in?
Extrahepatic mitochondria
Liver is NOT able to use ketone bodies
Deficient enzyme which hinders ketolysis to occur in hepatocytes?
Succinyl-CoA-Acetoacetate-CoA transferase (thiophorase)
Storage form of Cholesterol
Cholesteryl Esters
Cholesterol structure
27-Carbon compound
4 fused hydrocarbon rings
A ring has Hydroxyl group at C3
B ring has double bond between C5 and C6
D ring has 8 branched hydrocarbon chain at C17
Substrate of Cholesterol synthesis
Acetyl CoA
Cholesterol synthesis occurs in?
Cytosol and ER
Rate limiting step and enzyme of Cholesterol synthesis
HMG-CoA → Mevalonate
HMG-CoA Reductase
cHolesteRol
2 primary bile acids
Cholic and Chenodeoxycholic (CC)
2 Secondary bile acids
Deoxycholic and Lithocolic
Digested by bacteria
Enzyme that converts cholesterol to pregnenolone
Desmolase
Enzyme that converts cholesterol to 7-a-hydroxycholesterol
7-a-hydroxylase
How many percent of bile salts is reabsorbed in the intestine?
95%
Most common form of CAH
21 a- hydroxylase deficiency
CAH that presents with low renin hypertension
11-B1-hydroxylase deficiency
Lipoprotein with highest TAG content
Chylomicron
Lipoprotein with lowest protein content
Chylomicron
Lipoprotein with highest cholesterol content
LDL
Lipoprotein with highest protein content
HDL
Apolipoprotein mediates secretion of VLDL
APO B-100
Apolipoprotein mediates secretion of Chylomicrons
APO B-48
Apolipoprotein mediates uptake of Chylomicron
APO E
Apolipoprotein cofactor of lipoprotein lipase
APO C-II
Apolipoprotein cofactor of cholesterol acyltransferanse
Apo A-1
APO C II deficiency
Familial A. Lipoprotein Lipase Deficiency B. Hypercholesterolemia C. Dysbetalipoproteinemia D. Hypertriacylglycerolemia
Type I. Familial Lipoprotein Lipase def
Defective LDL receptor
Familial A. Lipoprotein Lipase Deficiency B. Hypercholesterolemia C. Dysbetalipoproteinemia D. Hypertriacylglycerolemia
Type IIa. Familial Hypercholesterolemia
Low LDL, low HDL, recurrent pancreatitis
Familial A. Lipoprotein Lipase Deficiency B. Hypercholesterolemia C. Dysbetalipoproteinemia D. Hypertriacylglycerolemia
Type I. Familial Lipoprotein Lipase def
High LDL and cholesterol + atherosclerosis
Familial A. Lipoprotein Lipase Deficiency B. Hypercholesterolemia C. Dysbetalipoproteinemia D. Hypertriacylglycerolemia
Type IIa. Familial Hypercholesterolemia
Abnormal Apo E
Familial A. Lipoprotein Lipase Deficiency B. Hypercholesterolemia C. Dysbetalipoproteinemia D. Hypertriacylglycerolemia
Type III. Familial Dysbetalipoproteinemia
High VLDL, High cholesterol, Low LDL, Low HDL
Familial A. Lipoprotein Lipase Deficiency B. Hypercholesterolemia C. Dysbetalipoproteinemia D. Hypertriacylglycerolemia
Type IV. Familial Hypertriacylglycerolemia
Hypolipoproteinemia present with Absent chylomicrons or VLDL
Abetalipoproteinemia
Hypolipoproteinemia present with absent HDL
Familial alphalipoproteinemia