Biochemistry and cell biology of long chain sphingosine bases and sphingolipids, galactocerebrosides and sphingomyelin

Genetics, cell biology and biochemistry of sphingolipid synthesizing and degrading enzymes: Cerebroside synthase (UDP-galactosyl-ceramide transferase, CGT), acid (SMPD-1) and neutral sphingomyelinases (SMPD-2 and SMPD-3).
Sphingosine bases, dihydrosphingosine and sphingosine (long chain bases) form the backbone molecule of complex sphingolipids, important building blocks of biological membranes, particularly of myelin of central and peripheral nervous system.

We unravelled the complete biosynthetic (A) and catabolic (B) pathways of long chain sphingosine bases.

A. The key enzyme in the biosynthesis of long chain sphingosine bases is palmitoyl-CoA serine transferase (SPT). Palmitoyl-CoA and serine are condensed to 3-keto-2S-sphinganine, which is reduced by 3-ketosphinganine reductase, a NADPH dependent enzyme, to sphinganine. After acylation to ceramide the trans double bond is introduced in the acyl-4trans-sphinganine desaturase reaction.

B. The degradation of the long chain bases is initiated by the ATP dependent sphingosine-kinase (SP-1-K) reaction to sphingosine-1-phosphate, which has been recognized as a potential lipid second messenger molecule. SP1-P is cleaved in a pyridoxal phosphate dependent aldolase reaction by SP-1-phosphate aldolase to palmitaldehyde and ethanolamine phosphate. The reutilization of these degradation products in the phospholipid synthesis has been established in this laboratory.

Literature

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