1-alkyldihydroxyacetone

This enzyme is an integral membrane protein exclusively localized to the lumenal side of peroxisomes (A. Poulos, 1993). Reports on the presence of this enzyme in other organelles are likely a result of peroxisomal contamination. This acyltransferase is important in ether lipid biosynthesis (Chapter 9). Once 1-acyldihydroxyacetone-P has been formed it can be used as a substrate for 1-alkyldihydroxyacetone-P synthesis (Chapter 9) or can be reduced to lyso-PA by a peroxisomal acyldihydroxyacetone-P reductase (Fig. 1) that also utilizes 1-alkyldihydroxyacetone-P as a substrate. 

Figure 2. Biosynthesis of plasmalogens in mammalian tissues. Enzymes (1) dihydroxyacetone phosphate acyltransferase (2) 1-acyldihydroxyacetone phosphate synthase (3) 1-alkyldihydroxyacetone phosphate oxidoreductase (4) l-alkyl-5n-glycero-3-phosphate acyltransferase (5) 1-afkyl 2-acyl-5w-glycero-3-phosphohydrolase (6) CDP-ethanolamine transferase (7) l-alkyl-2-acyl-5w-glycero-3-phosphoethanolamine desaturase (8) methyltransferases and base-exchange enzymes. CDP-ethanolamine, cytidine diphosphoethanolamine. CMP, cytidine monophosphate. CoA, coenzyme A. DHAP, dihydroxyacetone phosphate. NADH, nicotinamide adenine dinucleotide, reduced form. NAD, nicotinamide adenine dinucleotide, oxidized form. Pi, phosphate.

Peroxisome proliferators are also involved in two other metabolic pathways of importance to lipid metabolism. Peroxisomes contain the most of di-hydroxyacetone phosphate acetyltransferase and alkyldihydroxyacetone phosphate synthetase activities. Therefore, they are responsible for initiating most ether glycerolipid biosynthesis. These enzymes are also moderately induced by peroxisome proliferators. Induction of cytochrome P450s by peroxisome proliferators will be addressed separately. 

Peroxisomes contain dihydroxyacetone phosphate acyl-transferase and alkyldihydroxyacetone phosphate synthase, which are involved in synthesis of the plasmalogens (Chapter 19). Peroxisomes may also participate in the biosynthesis of bile acids. The conversion of trihydrox-ycholestanoic acid to cholic acid (Chapter 19) has been localized to peroxisomes. 

Fig. 5. Biosynthesis of membrane phospholipids from alkyldihydroxyacetone-P (alkyl-DHAP), the first detectable intermediate formed in the biosynthetic pathway for ether-linked glycerolipids. Enzymes catalyzing the reactions are (1) NADPH alkyl-DHAP oxidoreductase, (II) acyl-CoA 1 -alkyl-2-lyso-sn-glycero-3-phosphate acyltransferase, (III) l-alkyl-2-acyl-in-glycero-3-phosphate phosphohydrolase, (IV) ATP 1-alkyl- /i-glycerol phosphotransferase, (V) CDP-choline l-alkyl-2-acyl-sn-glycerol cholinephosphotransferase (dithiothreitol-sensitive), (VI) CDP-ethanolamine l-alkyl-2-acyI-sn-glycerol ethanolaminephosphotransferase, and (VII) acyl-CoA 1 -alkyl-2-acy 1-OT-glycerol acyltransferase.

Chae, K. Piantadosi, C. Snyder, R Reductase, phosphatase, and kinase activities in the metabolism of alkyldihydroxyacetone phosphate and alkyldi-hydroxyacetone. ]. Biol. Chem., 248, 6718-6723 (1973)... 

The biosynthesis of plasmalogens has been elegantly reviewed by several investigators (Paltauf, 1994 Lee, 1998 Nagan and Zoeller, 2001 Murphy, 2001). Briefly, the first three enzymes of plasmalogen biosynthesis (dihydroxyacetone phosphate acyltransferase, alkyldihydroxyacetone phosphate synthase, and acyl/alkyl dihydroxyacetone reductase) are located in peroxisomes. The other enzymes, namely l-alkyl- n-GroP acyltransferase, l-alkyl-2-acyl-5n-GroP phosphohydrolase, and l-alkyl-2-acyl-jn-Gro ... 

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