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Pathway · 8 proteins

Glycerolipid assembly

Glycerol-phosphate and acyl-transfer chemistry builds membrane lipids.

How it works

  1. Acylation starts from glycerol-3-phosphate, produced by an NAD(P)H-dependent glycerol-3-phosphate dehydrogenase, and loaded with an acyl chain by PlsY, a glycerol-3-phosphate 1-O-acyltransferase.
  2. Phosphatidate cytidylyltransferase activates phosphatidate with CTP, and CDP-alcohol phosphatidyltransferase family enzymes transfer the phosphatidyl group onto a second alcohol to form the phospholipid head group.
  3. Phosphatidylglycerophosphatase and a lysyl-phosphatidylglycerol synthase modify the head group afterwards, which changes the charge of the membrane surface. Which lipids an organism can make is set by the head-group enzymes it carries, and this list is that set.

Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.

Its proteins

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
CDP-alcohol phosphatidyltransferase family protein———207System only
Phosphatidate cytidylyltransferase2.7.7.41a 1,2-diacyl-sn-glycero-3-phosphate + CTP + H(+) = a CDP-1,2-diacyl-sn-glycerol + diphosphate—259Step named
Uncharacterized protein aq_1480———196Step named
Glycerol-3-phosphate dehydrogenase [NAD(P)+]1.1.1.94sn-glycerol 3-phosphate + NAD(+) = dihydroxyacetone phosphate + NADH + H(+)—324Step named
CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase2.7.8.5a CDP-1,2-diacyl-sn-glycerol + sn-glycerol 3-phosphate = a 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycero-3'-phosphate) + CMP + H(+)—178Step named
YutG/PgpA domain-containing protein———145Step named
Uncharacterized protein———289System only
Glycerol-3-phosphate acyltransferase2.3.1.275an acyl phosphate + sn-glycerol 3-phosphate = a 1-acyl-sn-glycero-3-phosphate + phosphate—192Step named

Origins

Could two-chain membrane lipids, built on glycerol phosphate, have formed before this pathway existed?

How it was discovered

  1. 1977Hargreaves and colleagues make phosphatidic acid and other lipids without enzymes in the laboratory.Ruiz-Mirazo et al., Prebiotic Systems Chemistry, PDF p. 5
Naturalistic proposal

Membranes of single-chain fatty acids can assemble in water. Because phospholipids are complex, most researchers assume the first membranes were simpler, made of fatty acids, alkyl phosphates or similar molecules.

Design analysis

The same review calls it very improbable that fatty acids, glycerol and phosphate were ever present together on the early Earth in high enough concentrations. Fatty-acid membranes are fragile and stable only within a narrow range of acidity and salt.

Phospholipids, with two chains on one glycerol phosphate, make membranes stable. Eight proteins of the minimal set assemble them.

From the books: Ruiz-Mirazo et al., Prebiotic Systems Chemistry, PDF p. 5; Deamer, Assembling Life, p. 56.

The wider question for this part of the cell: origins for building and maintaining the membrane.

Sources

Other pathways in this group: Lipid A and outer envelope · Fatty-acid elongation · Substrate recognition · Terpenoid backbone biosynthesis · Fatty acid biosynthesis · Lipopolysaccharide biosynthesis · Biosynthesis of various nucleotide sugars · Not yet placed in a pathway