Lipogenesis

Lipogenesis site

Cytosol and microsomes in some cells

Lipogenesis in adipose tissue is for

Storage of energy

Lipogenesis in small intestine for

Formation of chylomicrons

TAG mainly secreted in liver as

VLDL or very low density lipoprotein to outside liver

3 pathways of Lipogenesis

1) Glycerol phosphate pathway

2) Dihydroxyacetone phosphate (DHAP) pathway

3) 2-monoacyl glycerol pathway

glycerol phosphate pathway site

In liver or small intestine

glycerol phosphate pathway 3 steps

1) activate fatty acid

2) activate glycerol

3) combine 3 Acyl coA and 3 glycerol-3-p

Activation of fatty acid turns fatty acid into

Acyl CoA

Activation of fatty acid requires this enzyme

Thiokinase enzyme (Acyl CoA synthase enzyme)

Activation of glycerol turns glycerol into

Glycerol-6-phosphate

Activation of glycerol requires this enzyme

Glycerol kinase

1-acetyl transferase job in glycerol-p pathway

Turns glycerol-3-p to monoacylglycerol-p or lysophosphatic acid

2-acetyltransferase job in glycerol-p pathway

Turns lysophosphatidic acid into phosphatidic acid (diacylglycerol)

Phosphatase job in glycerol-p pathway

Turns phosphatidic acid into diacylglycerol

3-acyltransferase job in glycerol-p pathway

Turns diaglycerol into triaglycerol

Dihydroxyacetone phsophate pathway diffrence (compared to glycerol-p pathway)

1) DHAP reduced to give glycerol-6-p

2) DHAP converted to acyl DHAP the reduced to lysophosphatidic acid

Enzyme that reduces DHAP to glycerol-6-p

Glycerol phosphate dehydrogenase

2-mono glycerol pathway site

Small intestine

DHAP pathway site

Liver and adipose tissue

2-monoacyl glycerol pathway

2 MAG to 1, 2 diacyl glycerol to TAG

The glycerol pathway doesn’t happen in adipose tissue

Because it lacks glycerol kinase

Sources of fatty acids

Liver, small intestine, and adipose tissue are sources

FA in liver are mainly from

De novo synthesis of FA from acetyl CoA dervies from glycolysis

FA in adipose tissue mainly from

1) hydrolysis of TAG: chylomicrons (small intestine) and VLDL (liver) in plasma

2) De novo synthesis of FAs in adipose tissue from acetyl CoA derives from glucose

FA in small intestine from

Digestion of dietary lipids

sources of glycerol

Liver and intestine are sources

Glycerol in liver mainly from

1) adipose tissue hydrolysis

2) breakdown of TAG present in chylomicrons or VLDL

Glycerol in intestine from

Dietary lipids

Source of DHAP

Glycolysis

Sources of MAG in small intestine

Digestion of dietary TAG by pancreatic lipase

Regulation of Lipogenesis includes 2 things

1) availability of substrates and insulin

2) regulation of FA synthesis

High CHO diet causes Lipogenesis why?

Because insulin is released causing glycolysis which increases:

Glycerol and DHAP

Then HMP shunt is increased cause NADPH needed for de novo FA synthesis increases

De novo synthesis of FA increased by

By covalent modification: ACC

By allosteric modification: citrate

Both increase ACC and fatty acid synthase

Dietary TAGs provide — which shares in TAG synthesis in small intestine epithelial cells to form chylomicrons

FA, glycerol, MAG

Adipose tissue is what kind of tissue

Peripheral extrahepatic

ACC is activated by

Dephosphorylation

Covalent modification of Lipogenesis

Activate: insulin

Inhibit: adrenalin and glucagon

Insulin’s covalent modification

+phosphodiesterase

-adenyl cyclase which lowers cAMP hence no activated protein kinase

Together with +phosphatase dephosphorylation of ACC occurs

Boosting Lipogenesis

Adrenaline and glucagon’s covalent modification

+adenyl cyclase which increases cAMP so +protein kinase

Phosphorylation of ACC (inactive) so Lipogenesis decreased

Allosteric regulation

Allosteric activation: citrate

Allosteric inhibition: long chain FA (palmitate) and Malonyl CoA

Induction and repression of enzyme synthesis

Insulin: increases synthesis of acetyl CoA carboxylase and FA synthase

Antiinsulin hormones: decreases synthesis of acetyl CoA carboxylase and FA synthase