3-Ketosphinganine

Write a reasonable mechanism for the 3-ketosphinganine synthase reaction, remembering that it is a pyridoxal phosphate-dependent reaction. 

In the second step of the sphingolipid biosynthetic pathway, the carbonyl group of 3-ketosphinganine is reduced with NADPH to... 

Ketosphinganine (JS) synthetase Sphingosine synthesis palmitoyl-CoA + serine - KS + C02... 

Recall that sphingolipids in animals possess ceramide, a derivative of the amino alcohol sphingosine. The synthesis of ceramide begins with the condensation of pafrni-toyl-CoA with serine to form 3-ketosphinganine. This reaction is catalyzed by 3-ketosphinganine synthase, a pyridoxal-5 - phosphate-dependent enzyme. (Because... 

Figure 4 Pathway for the production of Cer, the lipid component of mammalian GSL. In the ER, palmitoyl-CoA is condensed with i-serine to produce ketosphinganine, which is then reduced, and acylated to form Cer.

De novo sphingolipid biosynthesis begins with the condensation of palmitoyl-CoA and L-serine (Fig. 6) to form 3-ketosphinganine catalyzed by serine palmitoyltransferase (SPT). 

A protein that would be a logical interaction partner for SPT is 3-ketosphinganine reductase, which catalyzes the next step of the sphingolipid biosynthetic pathway. The gene for this reductase has been identified in yeast (T. Beeler, 1998) and in mammals (FVTl) (A. Kihara, 2004), and the sequence has coil-coil motifs that might interact with a similar motifs on SPT. 

See also Fatty Acids, Table 10.1, Synthesis of Long Chain Fatty Acids, Fatty Acid Desaturation, Palmitate Synthesis from Acetyl-CoA, Biosynthesis of Sphingolipids, 3-Ketosphinganine... 

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