BIOC/DENT/PHCY 230

LECTURE 8

Transport and delivery of dietary lipids

dietary triacylglycerol (TAG) and cholesterol are delivered to target tissues by lipoproteins

the four main lipoproteins are:

chylomicrons

VLDL

LDL

HDL

each lipoprotein has a characteristic combination of lipids and apoproteins

chylomicrons and VLDL are the primary transporters of TAGs to target tissues

LDL and HDL are the primary transporters of cholesterol

Structure of a general lipoprotein

Lipoprotein lipase liberates free fatty acids from TAGs

Chylomicrons and VLDLs have apoprotein CII, which anchors the lipoprotein to lipoprotein lipase

Fatty acid synthesis excess carbohydrate is converted to fatty acids and TAGs

fatty acid synthesis occurs in the cytoplasm of a variety of cell types

synthesis of fatty acids is based around acetyl-CoA

acetyl-CoA is a precursor for malonyl-CoA

it is in the form of malonyl-CoA that most carbons are introduced into fatty acid synthesis

Synthesis of malonyl-CoA

In vertebrates:

fatty acid synthesis is catalysed by a multi functional enzyme, fatty acid synthase

fatty acid synthase contains all the enzyme activities required for the remainder of fatty acid synthesis

Synthesis of Acetyl-ACP and Malonyl-ACP

Acetyl-CoA and malonyl-CoA are attached to an acyl carrier protein (ACP)

Initiation of fatty acid synthesis

-oxidation

synthesis

NADPHNADP+ + H+

NADPHNADP+ + H+

Elongation continues with the addition of malonyl-CoA

8 acetyl-CoA + 14 NADPH + 7ATP

palmitate + 14 NADP+ + 8 CoA + 7ADP + 7 Pi + 6H2O

Overall equation for the synthesis of palmitate (16:0)

Synthesis of TAGs

fatty acids are added onto a glycerol backbone

glycerol -3- phosphate can be derived from:

DHAP (glycolysis)

phosphorylation of glycerol

by glycerol kinase

Regulation of fatty acid synthesis fatty acids synthesis can be regulated in a number of ways

acetyl-CoA carboxylase represents a major control point

acetyl-CoA

citrate

insulin

+-palmitoyl-CoA

glucagon

inactive dimer

active polymer

inactive acetyl-CoA carboxylase is found as a dimer

polymerisation activates the enzyme

Excess citrate is shuttled to the cytoplasm

glucose

NADH NADPH

NADPH supplies the reducing power for fatty acid biosynthesis

NADPH is generated by the Pentose Phosphate Pathway

The take home message

dietary lipids are delivered to target tissues by lipoproteins

excess fuels can be converted fatty acids

fatty acid synthesis has many features in common with -oxidation

acetyl-CoA carboxylase represents a major control point for fatty acid synthesis

reducing power in the form of NADPH is supplied by the pentose phosphate pathway