Download Cell structure and Bioenergetics

Basic and Metabolism
of Lipid
Donrawee Leelarungrayub (BSc, PT), (Ph.D. Biochem)
Department of Physical Therapy
Faculty of Associated Medical Sciences
Chiang Mai University, Chiang Mai, Thailand
Outline
1. Basic structure of Lipid
2. Basic of Lipid Metabolism; Oxidation and Synthesis
3. Regulation of Lipid Metabolism
4. Ketone Metabolism
5. Relationship between Glucose and Lipid Metabolism
Kinds and sources of Lipids
•
Simples lipids;
Nester of lipid and alcohol
• Fats
• Waxes
• Complex lipid
• Phospholipids: glycerophospholipids, sphingophospholipids
• Glycolipids = FA + sphogosine + CHO
• Lipoproteins: sulfolipids, aminolipids
• Derived lipids;
Fatty acids, Steroids, Hydrocarbons
Fatty acid
and Structure
Fatty acid = R-OOH
Common Fatty acid in Humans
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Palmitic acid
Stearic acid
Palmitoleic acid
Olieic acid
Linoleic acid
Linolenic acid
Arachidonic acid
C = 16
C = 18
C = 16
C = 18
C = 18
C = 18
C = 20
Short and Long chain of Fatty acid
Short chain (2-4 carbons) and medium chain (6-12 carbons)
- coconut oil, palm kernel oil = directly absorbed in small intestine,
transport to the liver through the portal vein
- diffuse freely without carnitine esterification into the mitochondria
 Long chain ( > 14 carbons)
- found in triglycerol (fat) and structural lipids
- require the carnitine shuttle to move form cytosol into the
mitochondria
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Unsaturated fatty acid
Double bonds in most naturally occurring fatty acid = cis
 Trans fatty acid = margarine and other hydrogenated vegetable oils
= risk factor to atherosclerosis
 Oxidation of unsaturation fatty acid in membrane lipids = membrane
damage => hemolytic anemia (Vit E deficiency)
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Phospholipid
Diacylgycerol with a phosphate group on the third glycerol carbon
– Major component of cellular membrane
 Phospholipase cleave specific bonds in phospholipid
– Phospholipase A1 and A2
– Phospholipase C
– Phospholipase D
 Lung surfactant : abundant phhospholipids, phosphatidylcholine
= Respiratory distress syndrome (RDS), hyaline membrane disease
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Sphingolipids
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Derivatives of ceramids, esterification of a fatty acid with amino
group of sphingosine
Localized mainly in the white matter of the central nervous system
Sphingomyelins => nerve cells and blood cells, signal transduction
Cerebrosides : galactose or glucose => myelin sheath
Gangliosides : oligosaccharide (sialic acid) => myelin sheath
Steroids
Lipid containing a ring system with a hydroxyl or ketone groups
 Cholesterol : cellular membrane, modulates membrane fluidity
 Precursor for synthesis of steroid hormones, skin-derived vitamin D,
and bile acids
– Cholesterol: 27 Carbons
– Bile acids: 24 carbons
– Androgens: 19 carbons
– Progesterone and adrenocortical steroids ; 21 carbons
– Estrogens: 18 carbons
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Eicosanoids
Eicosanoids function as short-range, short-term signaling molecules
– Arachidonic acid is released from membrane phospholipids by
phospholipase A2
 Prostaglandins
– Formed by the action of cyclooxygenase on arachidonic acid
– Prostaglandin H2 (PGH2) is the precursor for prostandins and
thromboxanes
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Prostaglandins
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Promote acute inflammations
Stimulate or inhibit smooth muscle contraction, depending on type and
tissue
Promote vasodilation (arterioles) or vasocontriction (cerebral vessels)
Pain in acute inflammation
Production of fever
Eicosanoid Pathway
Thromboxane A2 (TXA2)
Produced in platelets by the action of thromboxane synthase on
PGH2
 Strongly promotes arteriole contraction and platelet aggregation
 Aspirin and other non-steroidal anti-inflammatory drugs (NSIAD)
acetylate and inhibit cyclooxygenase, leading to reduced synthesis
of prostaglandins
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Triglycerides
- neutral fat
- glycerol + 3 ROOH
1. Highly concentrated energy reserve
2. Formed by esterification of fatty acids with glycerol
3. Excess fatty acids in diet and fatty acids synthezied
and stored in adipose cellls
Beta-Oxidation
1. Activation
2. Transfer acyl CoA to mt.
3. Beta-oxidation
4. TCA
5. NADH, FADH2 oxidation in ETS
Beta-Oxidation
1. Glucose ------- Acetyl CoA
GLUT4
2.
Regulation
Short term regulation – ACC , Glucogon
 Long term regulation – Insulin + ACC
-- Hormone sentitive lipase (HSL)
-- Carnitine acyltransferase I (CPTI)
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Lipoprotein Metabolism
Ketone bodies Metabolism
Ketone synthesis --- liver mitochondria
Blood - ketone bodies
Ketone body utilization – muscle kidney and brain
TCA
Metabolic regulation; lipolysis and lypogenesis
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Fed state: lipoprotein lipase
Fasting state; cAMP --- FA and glycerol
Exercise; adrenaline --- cAMP
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Sources;
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acetyl CoA
malonyl CoA
NADPH
PPP
Malate -- pyruvate