Nadp

Serine palmitoyltransferase

3-Ketosphinganine reductase

SpHnganine ch2oh

Fatty acyl-CoA CoASH

Ceramide synthase

Dihydroceramide

Fatty acyl-CoA CoASH

Dihydroceramide

,ch2oh

Cofactors?

,ch2oh

Cofactors?

"Desaturase"

Ceramide

,ch2oh

,ch2oh

Fig. 7.12 Biosynthesis of ceramide.

of palmitoyl-CoA with serine using a pyridoxal phosphate-requiring enzyme. The selectivity of the serine palmitoyltransferase accounts for the prevalence of 18C bases in most sphingolipids. Some very potent inhibitors of the reaction have been recently developed including a myriocin that is at least ten times better as an immunosuppressant than cyclosporin A.

3-Ketosphinganine is then reduced to sphinga-nine using NADPH. The desaturation of the hydrocarbon chain of sphinganine to yield sphin-gosine uses a flavoprotein enzyme - possibly analogous to the acyl-CoA dehydrogenase of P-oxidation (Section 2.3.1). However, it appears to take place after an N-acyl group has been attached to the base by ceramide synthase. The latter uses acyl-CoAs as donors (Fig. 7.12).

Potent inhibitors of ceramide synthase (fumoni-sins) are produced by some strains of Fusarium moniliforsue a very common contaminant of corn. Fumonisins cause important veterinary diseases (e.g. horse leukoencephalomalacia, pig pulmonary oedema) and have been implicated in human cancer. Similar mycotoxins are produced by fungi that grow on other plants.

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