Glycerophospholipid

In fungal microorganisms, as in other eukaryotes, there are two pathways for PC biosynthesis(Ref. 2014). In mammals, the major route for synthesis of PC is the CDP-choline pathway, while the methylation pathway apparently contributes to the synthesis of PC only in the liver(Ref. 2015). In CDP-choline pathway, free choline is phosphorylated and converted to CDP-choline, and then the phosphocholine moiety of CDP-choline is transferred to diacylglycerol for PtdCho formation. CDP-choline formation is rate limiting for PtdCho biosynthesis. In yeast and other fungi, however, the methylation pathway serves as the principle route for PC biosynthesis especially in cells growing in the absence of choline supp;ementation.
Under these conditions, PC is synthesized via a series of three sequential methylations of PE, catalyzed by the membrane-associated phospholipid N-methyltransferases(PLMTs). The two intermediates in this reaction series have been identified as PMME and phosphatidyl-dimethylethanolamine(PDME). Fungi, in contrast to mammals, have two PLMTs. Plants do not methylate PE, but can carry out the last two methylation steps to PC biosynthesis from PMME(Ref. 2016)

There are at least two major mechanisms by which dipalmitoyl-PC could be synthesized in the lung: (a) The initial acylations of sn-glycerol-3-P may be highly nonrandom, thereby producing large amounts of dipalmitoyl-PA whose acyl distribution pattern would be maintained through subsequent steps to the PC level. Dipalmitoyl-PC would, then, be produced as a consequece of the substrate and positional specificity of sn-glycerol-3-P acyltransferases. (b)The initial acylations of sn-glycerol-3-P may produce PA and, subsequently, PC species with varying degrees of randomness and asymmetry. The nonspecific fatty acid distribution pattern of these de novo produced PC species would then be modified to give dipalmitoyl-PC through the interaction of other enzymatic reacylation systems(Ref. 2028).

1-acyl-lyso-PC is formed from PC by the action of phosphlipase A₂ from various kinds of sources.

In mammalian cells, PtdSer is synthesized through the exchange of L-serine with choline moiety of phosphatidylcholine or ethanolamine moiety of phosphatidylethanolamine(Ref. 2208/2209). In bacteria and the yeast Saccharomyces cerevisiae, PtdSer is synthesized through transfer of the phosphatidyl moiety of CDP-diacylglycerol to L-serine(Ref. 2210/2211). Decarboxylation of PtdSer is an important pathway for phosphatidylethanolamine formation in both prokaryotes and eukaryotes(Ref. 2212).

N-methylphosphatidylethanolamine is the first intermediate of phosphatidylcholine synthesis from phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase(s) with S-adenosylmethionine serving as the methyl group donor. (Ref. 2414) This phospholipid is methylated and N,N-dimethylphosphatidylethanolamine, the second intermediate, and phosphatidylcholine are formed.

N,N-dimethylphosphatidylethanolamine is the second intermediate of phosphatidylcholine synthesis from phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase(s) with S-adenosylmethionine serving as the methyl group donor. This phospholipid is methylated and phosphatidylcholine is formed. Amino acid sequence of the enzymes of Saccharomyces cerevisiae (Ref. 2432) and rat liver (Ref. 2433) was reported.

N,N-dimethylphosphatidylethanolamine is the second intermediate of phosphatidylcholine synthesis from phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase(s) with S-adenosylmethionine serving as the methyl group donor (Ref. 2444). This phospholipid is methylated and phosphatidylcholine is formed (Ref. 2445).

1-Palmitoyl-2-lysophosphatidyl-N-methylethanolamine is methylated and 1-palmitoyl-2-lysophosphatidyl-N,N-dimethylethanolamine is formed by the phosphatidylethanolamine N-methyltransferase system with S-adenosylmethionine serving as the methyl group donor (Ref. 2452).

In eukaryotic cells, PE is synthesized by decarboxylation of phosphatidylserine (PS) or by the CDP-ethanolamine pathway. In the latter case, PE is synthesized from 1,2-diacyl-sn-glycerol and CDP-ethanolamine by ethanolaminephosphotransferase (E.C. 2.7.8.1). In bacteria, PE is synthesized by the decarboxylation pathway, while the CDP-ethanolamine pathway has not been confirmed. (Ref. 2466/2467/2472/2473/2474/2478) / PE is catabolized by phospholipases and lysoPE, phosphatidic acid, diglyceride etc. are made (Ref. 2474/2475/2476/2478). PE is also converted to PC through methylation pathway (Ref. 2473/2474/2477/2478).

1-acyl-LysoPE is synthesized from phosphatidylethanolamine by phospholipase A₂ and is decomposed by lysophospholipase (Ref. 2532/2533). This lipid is reacylated by acyl-CoA: lysophospholipid transferase (Ref. 2532/2533).

PG is produced by dephospholylation of phosphatidylglycerophosphate, which is synthesized by the condensation of CDP-diacylglycerol with glycerol 3-phosphate.(Ref. 2601)

metabolism in Mycobacterium smegmatis(Ref. 2806).

Biosynthesis(Ref. 2820/2821).

Proposed biosynthesis pathway is described(Ref. 2825)

LysoPl 4-phosphate is rapidly dephosphorylated to 1-acyl-sn-glycero-(3)-phospho-(1)-L-myo-inositol by rat brain and liver microsomes(Ref. 2828), and this phosphatase activity does not require divalent cations(Ref. 2829). The generation of lysoPl 4-phosphate is stimulated by insulin in isolated rat fat cells(Ref. 2830).

Acylation of lysoPl is detected in aderenals(Ref. 2835), brain(Ref. 2836/2837/2838), liver(Ref. 2839/2840),heart(Ref. 2841) and platelets(Ref. 2842). LysoPl is phosphorylated by human platelet microsomes(Ref. 2843) and by carrot membranes(Ref. 2844). LysoPl can be degraded by lysoPl-specific phospholipase C(Ref. 2845/2846/2847/2848/2849). LysoPl levels increase in RAW264.7 macrophage stimulated with lipid A precursors, LPS, PMA, or A23187(Ref. 2850) and in platelet stimulated with thrombin or A23187(Ref. 2851).

PI 5-phosphate is formed by phosphorylation of PI, the reaction catalyzed by PI 5-kinase (type I PIP kinase) in vitro(Ref. 2857/2858). PI 5-phosphate can be produced in vitro by dephospharylation of PtdIns(4,5)P₂(Ref. 2858/2859). PI 5-phosphate can be phosphorylated in vitro by PI 3-kinase, producing PtdIns(3,5)P₂ or by PIP 4-kinase (type II PIP kinase), producing PtdIns(4,5)P₂(Ref. 2858/2859)

PI 4-phosphate is formed by phosphorylation of PI, the reaction catalyzed by PI 4-kinase(Ref. 2861/2862/2863). PI 4-phosphate is also produced by dephosphorylation of PtdIns(4,5)P₂ and PtdIns(3,4)P₂(Ref. 2857). PI 4-phosphate is phosphorylated by PIP 5-kinase (type I PIP kinase), producing PtdIns(4,5)P₂ or in vitro by PI 3-kinase, producing PtdIns(3,4)P₂(Ref. 2857/2859).

PtdIns(4,5)P₂ is produced by phosphorylation of PtdIns4P, the reaction catalyzed by PIP 5-kinase (type I PIP kinase), and by phosphorylation of PtdIns5P, the reaction catalyzed by PIP 4-kinase (type II PIP kinase) (Ref. 2857/2859).PtdIns(4,5)P₂ can also be synthesized by dephosphorylation of PtdIns(3,4,5)P₃(Ref. 2857). PtdIns(4,5)P₂ is phosphorylated by PI 3-kinase, producing the second messenger PtdIns(3,4,5)P₃(Ref. 2868).

PI is biosynthesized by the condensation of CDP-diacylglycerol and myo-inositol, the reaction catalyzed by phosphoinositide-specific phospholipase C(Ref. 2895/2896/2897/2898/2899). In response to various stimuli, PI is phosphorylated by PI 3-kinase and PI 4-kinase, producing PtdIns3P and PtdIns4P, respectively(Ref. 2857). PI can also be phosphorylated by PIPKI (PI 5-kinase), producing PtdIns5P(Ref. 2858).