Page 179 - Color Atlas of Biochemistry

170 Metabolism

Biosynthesis of complex lipids The biosynthesis of most phospholipids
also starts from DAG.
[7] Transfer of a phosphocholine residue to
A. Biosynthesis of fats and phospholipids
thefreeOHgroup gives riseto phosphatidyl-
Complex lipids, such as neutral fats (triacyl- choline (lecithin; enzyme: 1-alkyl-2-acetyl-
glycerols), phospholipids, and glycolipids, are glycerolcholine phosphotransferase 2.7.8.16).
synthesized via common reaction pathways. The phosphocholine residue is derived from
Most of the enzymes involved are associated the precursor CDP-choline (see p. 110). Phos-
with the membranes of the smooth endoplas- phatidylethanolamine is similarly formed
mic reticulum. from CDP-ethanolamine and DAG. By
contrast, phosphatidylserine is derived from
The synthesis of fats and phospholipids phosphatidylethanolamine by an exchange of
starts with glycerol 3-phosphate.This com- the amino alcohol. Further reactions serve to
pound can arise via two pathways: interconvert the phospholipids—e. g., phos-
[1] By reduction from the glycolytic phatidylserine can be converted into phos-
intermediate glycerone 3-phosphate (dihy- phatidylethanolamine by decarboxylation,
droxyacetone 3-phosphate; enzyme: glyc- and the latter can then be converted into
erol-3-phosphate dehydrogenase (NAD+) phosphatidylcholine by methylation with S-
1.1.1.8), or: adenosyl methionine (not shown; see also
[2] By phosphorylation of glycerol deriving p. 409). The biosynthesis of phosphatidylino-
from fat degradation (enzyme: glycerol kinase sitol starts from phosphatidate rather than
2.7.1.30). DAG.
[3] Esterification of glycerol 3-phosphate [8] Inthe lumenof the intestine, fats from
with a long-chain fatty acid produces a food are mainly broken down into monoacyl-
strongly amphipathic lysophosphatidate (en- glycerols (see p. 270). The cells of the intesti-
zyme: glycerol-3-phosphate acyltransferase nal mucosa re-synthesize these into neutral
2.3.1.15). In this reaction, an acyl residue is fats. This pathway also passes via DAG
transferred from the activated precursor (enzyme: acylglycerolpalmitoyl transferase
acyl-CoA to the hydroxy group at C-1. 2.3.1.22).
[4] A second esterification of this type leads [9] Transfer of a CMP residue gives rise first
to a phosphatidate (enzyme: 1-acylglycerol-3- to CDP-diacylglycerol (enzyme: phosphatida-
phosphate acyltransferase 2.3.1.51). Unsatu- tecytidyl transferase 2.3.1.22).
rated acyl residues, particularly oleic acid, [10] Substitution of the CMP residue by
are usually incorporated at C-2 of the glycerol. inositol then provides phosphatidylinositol
Phosphatidates (anions of phosphatidic acids) (PtdIns;enzyme: CDPdiacylglycerolinositol-3-
are the key molecules in the biosynthesis of phosphatidyl transferase 2.7.8.11).
fats, phospholipids, and glycolipids. [12] An additional phosphorylation (en-
[5] To biosynthesize fats (triacylglycerols), zyme: phosphatidylinositol-4-phosphate kin-
the phosphate residue is again removed by ase 2.7.1.68) finally provides phosphaditylino-
hydrolysis (enzyme: phosphatidate phospha- sitol-4,5-bisphosphate (PIP 2 ,PtdIns(4,5)P 2 ).
tase 3.1.3.4). This produces diacylglycerols PIP 2 is the precursor for the second messen-
(DAG). gers 2,3-diacylglycerol (DAG) and inositol-
[6] Transfer of an additional acyl residue to 1,4,5-trisphosphate (InsP 3 ,IP 3 ; see p. 367).
DAG forms triacylglycerols (enzyme: diacyl- The biosynthesis of the sphingolipids is
glycerol acyltransferase 2.3.1.20). This com- shown in schematic form on p. 409.
pletes the biosynthesis of neutral fats. They
are packaged into VLDLs by the liver and re-
leased into the blood. Finally, they are stored
by adipocytes in the form of insoluble fat
droplets.

Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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