Dihydroxyacetone phosphate to a fat: reduction, three acylations and one dephosphorylation
Route: Dihydroxyacetone phosphate → sn-Glycerol 3-phosphate → 1-Palmitoyl-sn-glycerol 3-phosphate (lysophosphatidate) → 1,2-Dipalmitoyl-sn-glycerol 3-phosphate (phosphatidate) → 1,2-Dipalmitoyl-sn-glycerol (diacylglycerol) → Tripalmitin (triacylglycerol)
Glycerol 3-phosphate is formed mainly by reducing dihydroxyacetone phosphate (DHAP) with NADH, and to a lesser extent by phosphorylating glycerol. Two acyl groups are then added from acyl-CoA. The first acylation gives lysophosphatidate and the second gives phosphatidate. A phosphatidic acid phosphatase removes the phosphate group and leaves a diacylglycerol, and diacylglycerol acyltransferase adds the third acyl group to give a triacylglycerol. The last two enzymes are associated in a complex bound to the endoplasmic reticulum membrane, and the liver is the main site of triacylglycerol synthesis. The phosphatase, also called lipin 1 in mammals, sets how much phosphatidate goes to triacylglycerol and how much to phospholipids. The drawings put palmitoyl (16:0) on every position as a stand-in; in most phosphatidates the chain on carbon 1 is saturated and the chain on carbon 2 is unsaturated. Palmitoyl-CoA stands for any long-chain acyl-CoA, and the one-atom stub is the CoA residue. The textbook assigns both acylations to glycerol phosphate acyltransferase. Here they are two steps, with the separate EC numbers 2.3.1.15 and 2.3.1.51. The first card shows glycerol-3-phosphate acyltransferase 1 and the second shows an acyltransferase with the activity of the second step. No structure of lipin 1 is available, so the phosphatase card shows lipid phosphate phosphatase 1. It belongs to a different class of phosphatidate phosphatases and shares the EC number.
Practice this pathway All pathways
| Step | Enzyme | EC | In | Out |
|---|---|---|---|---|
| 1 | Glycerol-3-phosphate dehydrogenase (NAD, cytoplasmic) | 1.1.1.8 | NADH | NAD⁺ |
| 2 | Glycerol-3-phosphate acyltransferase | 2.3.1.15 | Palmitoyl-CoA | CoA-SH |
| 3 | 1-Acylglycerol-3-phosphate acyltransferase | 2.3.1.51 | Palmitoyl-CoA | CoA-SH |
| 4 | Phosphatidate phosphatase | 3.1.3.4 | H₂O | Pᵢ |
| 5 | Diacylglycerol acyltransferase 1 | 2.3.1.20 | Palmitoyl-CoA | CoA-SH |
Build any of these from its atoms.
Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).