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

Types of lipids• Compound lipids

– Neutral fats with other chemicals

• 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

Lipoproteins• Formed mainly in the liver• Consist of

– 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

•Classified according to their density•HDL: Least amount of cholesterol

•Carry cholesterol back to the liver•Converted to bile

•Most recycled, some excreted

Lipoproteins

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

Lipid metabolism• Phospholipase A2

– Capillary endothelium– Breaks down surface

lipoproteins

• Lecithin-cholesterol acyltransferase (LCAT)– Plasma– Forms a fatty acid-

cholesterol ester– This is transferred to

chylomicron or VLDL– Helps maintain stability of

those molecules as triglycerides are removed

Derived lipids

• Cholesterol– Only in animal products– In every cell of the body

• Cell membrane• Vitamin D• Hormones

– Testosterone– Estrogen– Cortisol

• Bile– Fat metabolism

– Found in• 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 synthesisFatty 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

• 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 acetyl-CoA, 1 NADH and 1 FADH

– Each acetyl CoA = 12 ATP– Each NADH = 3 ATP– Each FADH = 2 ATP

• Total for 16C palmitic acid?