LIPID METABOLISM

SOURCES OF TRIACYLGLYCEROLS

Diet

De novo biosynthesis

Storage depots in adipocytes

DIGESTION, ABSORPTION, and TRANSPORTATION

Major problem: insolubility in aqueous environment

Solution: bile salts and formation of lipoproteins

BILE SALTS

Detergent substances synthesized in the liver and stored in the gallbladder

Essential in lipid digestion Made up of a bile acid and an associated

cation. Bile acids are derived from cholesterol Bile salts are amphipatic

LIPOPROTEINS

Several types classified according to their density

Lipoproteins in each class contain characteristic apoproteins and have distinct lipid compositionAPOPROTEIN-a protein w/o its characteristic prosthetic group

Higher lipid abundance, lower density

Together, the lipoproteins help maintain in emulsified form some 500 mg of total lipid per 100 ml of human blood in the post absorptive state

TRANSPORT AND UTILIZATION

CHYLOMICRONS – from intestines to peripheral tissues (heart, muscle, adipose)

VLDL – for TAGs synthesized in the liver IDL – derived from VLDL LDL – principal form in which cholesterol

is transported to tissues HDL – returns excess cholesterol from

tissues to liver for metabolism or excretion

PA NCREATIC LIPASE

an unusual calcium-requiring enzyme that catalyzes a reaction at an oil-water interface

Acts via an active site serine and an acyl-enzyme intermediate

Products of fat digestion comprise a mixture of glycerol, free fatty acids, monoacylglycerol, and diacylglycerol

Resynthesis of TAGs occurs in the ER and Golgi complex of mucosal cells

TAGs emerge into the lymph system complexed with protein to form the lipoproteins called CHYLOMICRONS

MOBILIZATION OF FAT The capacity to store fat is unlimited but

the release of fat from storage depots is controlled hormonally

The first step of mobilization is the hydrolysis of TAG into glycerol and FFA

This step is controlled by a cascade involving cAMP

ACTIVATORS: epinephrine (stress) or glucagon (fasting)

MOBILIZATION OF FAT Hormone-receptor interaction activates adenylate

cyclase which in turn activates cAMP. cAMP activates protein kinase A phosphorylates

triacylglycerol lipase (hormone-sensitive lipase) which catalyzes the hydrolytic release of FA from C1 or C3

The TAG hydrolysis products exit the adipocyte by passive diffusion, goes to the blood plasma, and bind to albumin

Each molecule of albumin can bind up to 10 molecules of FFA

FATTY ACID ACTIVATION and TRANSPORT

Fatty acids are present in the cytosol FA oxidation occurs in the inner

mitochondria Fatty acyl-CoA is the active form The reaction is catalyzed by fatty acyl CoA

synthetase which are length-specific Activation is a two-step process (outer

mitochondria)

BETA-OXIDATION PATHWAY

Each series of steps acetyl CoA is produced

4 steps per cycle The acetyl CoA produced will enter the

Kreb’s cycle, where it is oxidized into CO2