Studies on the biosynthesis and degradation of sphingosine bases

Our studies in vivo and in vitro on the biosynthesis and the degradation of long chain sphingosine bases allow now to formulate the following reaction sequences. In the biosynthesis palmitoyl-CoA and L-serine are condensed with the pyridoxal phosphate dependent 3-dehydrosphinganine-L-serine synthetase with decarboxylation to yield 2S-3-dehydrosphinganine. The 3-keto-group is reduced by a NADPII dependent D-3-dehydrosphinganine reductase to D-erythro or 2S,3R-sphinganine. The B-side hydride ion is transferred to the 3-keto-group. Both enzymes are microsomal lipoprotein enzymes, of which so far the reductase has been purified 84 fold. The degradation of sphinganine is initiated with a kinase reaction yielding the sphinganine-1-phosphate ester. This is cleaved by a pyridoxal phosphate dependent sphinganine-1-phosphate:phosphoryl ethanolamine lyase to palmitaldehyde and phosphoryl ethanolamine. These cleavage products are preferably reutilized for the synthesis of phosphatidyl ethanolamine and alkenyl phospholipids. Finally the biosynthetic and degradation pathway taken together represent an additional route of serine transformation for the synthesis of the hydrophilic part of phospholipids.