Alkyl-DHAP synthase

Alkyl-dihydroxyacetone phosphate (DHAP) synthase Isolated alkyl-DHAP synthase deficiency... 

Formation of the alkyl ether bond in glycerolipids is catalyzed by alkyl-DHAP synthase (Fig. 4B). This reaction, which forms alkyl-DHAP as the first committed intermediate... 

Fig. 4. Ether phospholipid synthesis from dihydroxyacetone-phosphate. (A) Dihydroxyacetone-P acyl transferase (DHAPAT). The first step of ether phospholipid synthesis is catalyzed by peroxisomal DHAPAT. This enzyme is a required component of complex ether lipid biosynthesis and its role cannot be assumed by a cytosolic enzyme that also forms acyldihydroxyacetone-P. (B) Ether bond formation by alkyl-DHAP synthase. The reaction that forms the 0-alkyl bond is catalyzed by alkyl-DHAP synthase and is thought to proceed via a ping-pong mechanism. Upon binding of acyl-DHAP to the enzyme alkyl-DHAP synthase, the pro-f hydrogen at carbon atom 1 is exchanged by enolization of the ketone, followed by release of the acyl moiety to form an activated enzyme-DHAP complex. The carbon atom at the 1-position of DHAP in the enzyme complex is thought to carry a positive charge that may be stabilized by an essential sulfhydryl group of the enzyme thus, the incoming alkox-ide ion reacts with carbon atom 1 to form the ether bond of alkyl-DHAP. It has been proposed that a nucleophilic cofactor at the active site covalently binds the DHAP portion of the substrate.

Kinetic experiments with a partially purified enzyme from Ehrlich ascites cells and with recombinant protein suggest that the reaction catalyzed by alkyl-DHAP synthase involves a ping-pong mechanism, with an activated enzyme-DHAP intermediary complex playing a central role [26]. The existence of this intermediate would explain the reversibility of the reaction since the enzyme-DHAP complex can react with either fatty alcohols (forward reaction) or fatty acids (back reaction) (Fig. 4). Acyl-DHAP acylhydrolase does not... 

Patients with the clinical picture of classical RCDP but with isolated deficiencies of DHAPAT and alkyl-DHAP synthase have also been described (see [10] for review). In these patients phytanic acid is normal, which would suggest that distinction between classical RCDP and the two variants... 

Rhizomelic) chondrodysplasia punctata (RCDP) type 3 (alkyl-DHAP synthase deficiency) Alkyl-DHAP synthase Generalized 2q31 600121... 

Table 25,2, Rhizomelic chondrodysplasia punctata type 1 CPex7-deficiency) (25,5), type 2 (DHAPAT deficiency) (25,6) and type 3 (alkyl-DHAP synthase deficiency) (25.7) classical forms (80/10/10 patients) ...

Ether phospholipids are important cell membrane biomolecules involved in signal transduction, neuroplasticity, tumor growth, and membrane fluidity and trafficking." Alkyidihydroxyacetonephosphate synthase (ADPS) is an FAD-containing protein that catalyzes the formation of the ether bond of ether phospholi-pids." " Alkyidihydroxyacetonephosphate (alkyl-DHAP) is formed by exchange of the acyl moiety of acyl-DHAP with a fatty alcohol (Equation (20)). 

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.

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