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Lipid metabolism
Roles of lipids
• Largest energy
store
• Insulation
• Structural
components
– Membranes
– Hormones
• Carrier
– Fat-soluble
vitamins
Types of lipids
• Simple lipids
– Mostly
triglycerides
• Principal storage
form
• >95% of body fat
– Mostly in
adipose cells
– Some in liver
and skeletal
muscle
• Triglyceride
– One glycerol
– 3 fatty acids
• All have linear C
chain
• 14-22 C long
• Saturated or
unsaturated
• Compound lipids
– Neutral fats with other
chemicals
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Glycolipids
Sphingolipids
Phosphoglycerides
Lipoproteins
– Glycolipids
• Glycerol, two fatty acids and
one sugar group
• Involved in cell recognition
– Sphingolipids
• One fatty acid and one
molecule of sphingosine
• Sphingomyelin
– Signal transmission and cell
recognition
– Phosphoglycerides
• Glycerol, two fatty acids, one
phosphate group and one
alcohol group
– Important component of cell
membranes
Types of lipids
Lipoproteins
• Formed mainly in the
liver
• Consist of
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–
–
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Triglycerides
Phospholipids
Cholesterol
Protein
• Main transport form of
lipids in the blood
– Fats are insoluble in
water
– The protein and
phospholipids allow the
insoluble fatty acids to be
carried in the core of the
lipoprotein
Lipoproteins
•Classified according to their density
•HDL: Least amount of cholesterol
•Carry cholesterol back to the liver
•Converted to bile
•Most recycled, some excreted
Lipoproteins
• LDL and VLDL:
– Carry most of the cholesterol
– Have the greatest affinity for the arterial walls
• Particularly oxidized LDL
• Chylomicrons:
– Largest amount of triglycerides
– Produced in small intestinal cells
• Elevated after high fat meals
Lipid metabolism
• Triglycerides
– Not taken up directly
into the cells
– Must be broken down
first
• Fatty acids and glycerol
• Lipoprotein lipase
– Located on capillary
endothelium
• Glycerol goes to liver
• Phospholipase A2
– Capillary endothelium
– Breaks down surface
lipoproteins
• Lecithin-cholesterol
acyltransferase (LCAT)
– Plasma
– Forms a fatty acidcholesterol ester
– This is transferred to
chylomicron or VLDL
– Helps maintain stability of
those molecules as
triglycerides are removed
Lipid metabolism
Derived lipids
•
Cholesterol
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–
Only in animal products
In every cell of the body
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Cell membrane
Vitamin D
Hormones
–
–
–
•
Bile
–
–
Fat metabolism
Found in
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•
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Testosterone
Estrogen
Cortisol
Egg yolks
Meats, shellfish and dairy
Diets high in saturated
fats
•
Increase cholesterol
synthesis
Fatty acid synthesis
• Occurs in the liver and
adipose tissue
– Essentially
• Acetyl-CoA + 7 Malonyl-CoA +
NADPH + 14H+ → Palmitic Acid +
8CoA + 14 NADP+ + 6H2O
– Acetyl-CoA and Malonyl-CoA
are reduced to Palmitic acid
– NADPH is the reducing agent
– Dehydration Rx
– Malonyl-CoA
• Created from Acetyl-CoA
– Acetyl-CoA carboxylase
• Thus, anything that
increases Acetyl-CoA levels
can lead to fat synthesis
Triglyceride synthesis
Fatty acyl CoA
Triglyceride synthesis
• Glycerol 3 phosphate + 2
Fatty acyl-CoA
– Phosphatidic acid
• Phosphatidic acid
converted to diacylglycerol
– Phosphatase
• Diacylglcerol + fatt acyl
CoA
– Triglyceride
• Acyl transferase
Triglyceride metabolism
• Stored in
– Adipose tissue, liver,
muscle
• Breakdown process
– Lipolysis
– Whether or not triglycerides
come from muscle or liver,
same basic steps occur
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Mobilization
Circulation
Uptake
Activation
Translocation
B-oxidation
Aerobic metabolism
Lipid mobilization
• Hormone sensitive lipase
– Breaks down stored triglycerides
– Fatty acids and glycerol released
•
Into blood (adipose tissue)
– Glycerol
•
Goes to liver
–
–
–
Gluconeogenesis
Glycogenesis
Lipid biosynthesis
– Fatty acids
• Require a carrier
–
Albumin
Lipid Mobilization
• Activation of Hormone
sensitive lipase
– Epinephrine
• Activates G protein
– Stimulates adenylate
cyclase
– Adenylate cyclase
• Produces cAMP
– Activates Protein kinase A
Lipid circulation
• Fatty acids bound to
albumin
– Circulate around to active
tissues
• How do they know?
Fatty acid uptake
• Uptake
– Directly related to
circulating
concentration
– Rate of blood flow
• Increased flow,
increased delivery,
increased uptake and
utilization
– Requires
• Fatty acid transporter
(FAT) and Fatty acid
binding protein (FABP)
– Costs
• Two ATP
Fatty acid activation
• Fatty acids must be
activated
– ATP + CoA
• Fatty acyl-CoA
• Fatty acyl-CoA must
be translocated
– From cytoplasm to
mitochondria
• Carnitine acyl transferase
1 and 2
Fatty acid oxidation
• B-oxidation
– Sequential events which
• Convert fatty acyl-CoA to
– Acetyl-CoA
– NADH
– FADH
– Number of cycles
• (Number of carbon atoms/2)-1
• 16C FA
– 7 cycles
– Each cycle produces 1 acetylCoA, 1 NADH and 1 FADH
– Each acetyl CoA = 12 ATP
– Each NADH = 3 ATP
– Each FADH = 2 ATP
• Total for 16C palmitic acid?