Dihydroxyacetone phosphate acyltransferase

ALDP, DHAP, dihydroxyacetone phosphate DHAPAT, dihydroxyacetone phosphate acyltransferase NALD, neonatal adrenoleukodystrophy RCDP, rhizomelic chondrodysplasia punctata X-ALD, X-linked adrenoleukodystrophy ZS, Zellweger s syndrome. 

DIHYDROXYACETONE PHOSPHATE ACYLTRANSFERASE ENOYL-CoA HYDRATASE (or, CROTONASE)... 

Classical rhizomelic chondrodysplasia punctata (RCDP) patients have a marked shortening of their proximal extremities, calcified stippling of the epiphyses and cataracts in addition to their absent psychomotor development. Patients with a variant form of RCDP have normal bones, but will have cataracts and some degree of mental retardation. Patients with a deficiency of dihydroxyacetone phosphate acyltransferase are clinically indistinguishable from the classical RCDP phenotype. 

D-bifunctional protein deficiency [5], 2-methyl acyl-CoA racemase (AMACR) deficiency [3] and sterol carrier protein (SCP-x) deficiency [6], the disorders of etherphospholipid biosynthesis (dihydroxyacetone phosphate acyltransferase and alkyl- dihydroxyacetone phosphate synthase deficiency) [2], the disorders of phytanic acid alpha-oxidation (Refsum disease) [15], and the disorders of glyoxylate detoxification with hyperoxaluria type 1 as caused by alanine glyoxylate aminotransferase deficiency as a sole representative. 

Webber K. O. and Hajra A. K. (1993). Purification of dihydroxyacetone phosphate acyltransferase from guinea pig liver peroxisomes. Arch. Biochem. Biophys. 300 88-97. 

Hajra, A.K. 1997. Dihydroxyacetone phosphate acyltransferase. Biochim. Biophys. Acta 1348 27-34. 

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 ... 

CDP-choline (CDP-ethanolamine) choline (ethanolamine) phosphottansferase, are localized in the endoplasmic reticulum. The acylation of dihydroxyacetone phosphate (DHAP) by acyl-coenzyme A (acyl-CoA) is catalysed by dihydroxyacetone phosphate acyltransferase with formation of... 

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.

Very-long-chain fatty acids (VLCFA), trihydroxycholestanoic acid (THCA), phytanic acid and pristanic acid can all be measured in plasma/serum (> 1 ml). From the same blood sample erythrocytes, platelets and/or leukocytes can be prepared for determination of plasmalogens and dihydroxyacetone-phosphate acyltransferase (DHAPAT), respectively. 

This enzyme [EC 2.3.1.42], also known as glycerone-phosphate O-acyltransferase, catalyzes the reaction of an acyl-CoA with dihydroxyacetone phosphate (or, glyc-erone phosphate) to produce coenzyme A and an acyldi-hydroxyacetone phosphate (or, an acylglycerone phosphate). The acyl-CoA derivatives of pahnitate, stearate, and oleate can all be utilized as substrates, with highest activity observed with palmitoyl-CoA. 

The acylation of dihydroxyacetone phosphate and the subsequent reduction of acyldihydroxacetone phosphate to monoacylphosphatidic acid provides an alternative route for phosphatidic acid synthesis. Acyltransferases which utilize dihydroxyacetone phosphate have been purified from several sources (Bell and Coleman, 1982). However, the relative contributions of dihydroxyacetone phosphate and glycerophosphate to phosphatidic acid synthesis remain controversial (O Doherty, 1978). 

LPA can be produced by several enzymatic routes (Figure 4). However, the relative contributions of these to LPA production is not known since specific inhibitors for many of the enzymes involved are not available (Pages et al., 2001). Firstly, de novo biosynthesis of LPA occurs by acylation of glycerol 3-phosphate, catalysed by glycerophosphate acyltransferase, in both the endoplasmic reticulum and mitochondria. Alternatively, LPA can be synthesized by the phosphorylation of monoacylglycerol or, in peroxisomes, by the reduction of acyl dihydroxyacetone phosphate. Subsequently, acylation of LPA by monoacylglycerolphosphate acyltransferase produces the precursor of all glycerophospholipids, phosphatidic acid. The latter can also act as a precursor of LPA synthesis by phospholipase A-catalysed deacylation. 

---