METABOLISM OF ACYLGLYCEROLS

Synthesis of Triacylglycerol (TAG)

Site:

liver (secreted as VLDL) adipose tissue (storage of energy) intestine Substrates: fatty acyl CoA + glycerol-3-P Source of glycerol-3-P glycerol (liver) dihydroxy acetone phosphate (adipose tissue)

Formation of Glycerol 3-phosphate

Catabolism of Triacylglycerol
TAG lipase fatty acid + glycerol taken up by tissue oxidation esterification glycerol-3-p (glycolysis / gluconeogenesis)

Compound lipids
Phospholipids:

lecithin Cephalin phosphatidyl inositol Cardiolipin sphingomyelin

Ether

lipids: Plasmalogen

platelet activating factor Glycolipids: cerebrosides, gangliosides

Synthesis of Phospholipids
Phosphatidyl

choline / ethanolamine

+ 1,2-diacylglycerol

Phosphatidyl inositol
1,2-diacylglycerol phosphate (phosphatidate)

Phosphatidyl inositol: second messenger

Cardiolipin (diphosphatidyl glycerol)

Cardiolipin
Site:

mitochondria (inner membrane) Function: functioning of phosphate transporter cytochrome oxidase activity

Ether lipids
Plasmalogens

Platelet

Activating factor (PAF)

(1-alkyl-2-acetyl-sn-glycerol-3-phosphocholine)

Synthesis:

Peroxisome

 Platelet

Activating factor functions: Aggregates platelets Hypotensive and ulcerogenic properties. Inflammation, chemotaxis

 Phospholipase

degradation of phospholipids types: Phospholipase A1, A2, B, C, D

PL C: bacterial toxin hydrolyze PIP2 and produces second messengers PL D: signal transduction

Phospholipase A2:

present in snake and bee venom found in pancreatic fluid Functions: release arachidonic acid from membrane phospholipids lecithin lysolecithin + FA Inhibited by steroids

Phospholipase: mechanism of action

Degradation of phosphatidyl choline

Sphingolipids
Sphingomyelin

composition: fatty acid ceramide sphingosine phosphoric acid choline Ceramide synthesis: endoplasmic reticulum precursor: serine

Synthesis of ceramide

 Ceramide

functions act as second messenger regulates: apoptosis cell cycle cell differentiation cell aging

Synthesis of sphingomyelin

Sphingomyelin degradation
sphingomyelin
Sphingomyelinase

phosphoryl choline + ceramide

ceramidase

sphingosine + fatty acid

 Niemann

Pick disease enzyme deficient: sphingomyelinase clinical features: hepato splenomegaly mental retardation

Glycolipids
Cerebrosides

glucosyl ceramide: extraneural tissue galactosyl ceramide: myelin Synthesis:

Functions: cell adhesion cell recognition regulate cell growth / development source of blood group antigens / tumor antigens

Disorders
Gauchers

disease enzyme deficient: -glucosidase accumulation of glucosyl ceramide Krabbes disease enzyme deficient: -galactosidase accumulation of galactosyl ceramide

Ganglioside: synthesis

Globoside

Site: nerve endings Function: act as receptors for bacterial toxins (eg: cholera toxin)

 Tay

Sachs disease enzyme deficient: hexosaminidase accumulation of GM2 ganglioside clinical features: blindness muscle weakness

Sphingolipidoses (lipid storage diseases)

 Multiple

sclerosis demyelinating disease loss of phospholipids and sphingolipids from white matter diagnosis: C.S.F: phospholipid levels

Metabolism of unsaturated fatty acids

Classification
Mono

Unsaturated fatty acids (MUFA) eg: oleic acid, nervonic acid

Poly

Unsaturated fatty acids (PUFA) eg: linoleic acid, linolenic acid arachidonic acid

 Oleic

acid / palmitoleic acid not essential in the diet synthesized by introducing double bond at 9 position of saturated fatty acid

Linoleic / linolenic acid Cannot be synthesized in the body Double bonds can be introduced at the 4, 5, 6, and 9 positions No enzymes to introduce double bonds beyond the 9 position. supplied through diet