bds sphingolipid synthesis

Sphingolipid Synthesis

ByDr. C.I. Nyamwange

• The biosynthesis of sphingolipids takes place in four stages: 1. Synthesis of the 18-carbon amine sphinganine from

palmitoyl-coa and serine;

2. Attachment of a fatty acid in amide linkage to yield N-acylsphinganine;

3. Desaturation of the sphinganine moiety to form n-acylsphingosine (ceramide); and

4. Attachment of a head group to produce a sphingolipid such as a cerebroside or sphingomyelin

1

Sphingolipids are then made from ceramide which is synthesized in the endoplasmic reticulum from the amino acid serine

• Gangliosides are synthesized from ceramide by the stepwise addition of activated sugars (eg, UDPGlc and UDPGal) and a sialic acid, usually N-acetylneuraminic acid

Phospholipid biosynthesis

This pathway is located in peroxisomes.

• The synthesis pathway of phospholipids starts by reducing dihydroxyacetone phosphate to glycerol phosphate, with NADH as the reductant

• Alternatively, existing glycerol molecules may be phosphorylated by glycerol kinase.

• This is followed by two successive additions of acyl ester. Fatty acid (typically 16-18 C atoms) is first converted to the active CoA thioester by acyl CoA synthetase:

• The last product, 1,2-diacylglycerol-3-phosphate, is also known as phosphatidic acid, and its phospholipid derivatives are phosphatidyl-X. Phospholipids also tend to have a saturated fatty acid in position 1 and an unsaturated fatty acid in position 2.

• Phospholipid precursors are activated by forming a cytidine diphosphate derivative

• CDP-diacylglycerol contains a high energy bond between the two phosphates, so can act as a donor of diacylglycerol (bond breaks between glycerol and phosphate) or as a donor of the phosphatidyl radical

• Microorganisms use the head group hydroxyl compound to displace CMP and then link up to the phosphatidyl radical.

• The amino acid serine , which has a hydroxyl group side chain provides the head group for the negative phospholipid, phosphatidyl serine .

• Phosphatidyl serine can then be decarboxylated to produce the important neutral phospholipid, phosphatidyl ethanolamine.

• In animals, phosphatidyl ethanolamine and phosphatidyl choline are made by a different strategy, in which ethanolamine and choline are activated as CDP ethanolamine and CDP choline

• Diacylglycerol then displaces CMP to bond to the phosphate attached to the headgroup, as shown for the synthesis of phosphatidyl choline, a major animal phospholipid.

• The strategy used in animals is optimized for what is called salvage synthesis, in which existing molecules of ethanolamine, choline and diacylglyerol are reused.

Phosphatidyl ethanolamine + serine

phosphatidyl serine + ethanolamine

phosphatidyl ethanolamine

CO2 phosphatidyl serine decarboxylase

phosphatidyl ethanolamine serine transferase

Decarboxylation of phosphatidyl serine produces new molecules of ethanolamine.

The “salvage” pathway from phosphatidylserine tophosphatidylethanolamine and phosphatidylcholine

New molecules of choline are made on the phospholipid structure of phophatidyl ethanolamine.The methyl donor is a compound is S-adenosyl methionine or SAMfor short, leaving behind S-adenosylhomocysteine, SAHC

Pathway for phosphatidylcholine synthesis from choline in mammals.