Plasmalopsychosine, a novel plasmal (fatty aldehyde) conjugate of psychosine with cyclic acetal linkage. Isolation and characterization from human brain white matter.
Through a systematic examination of basic (cationic) lipids separated on Folch's lower phase from extracts of human brain by cation exchange chromatography on carboxymethyl Sephadex in a chloroform/methanol mixture, followed by successive chromatographies on Florisil and Iatrobeads columns, five compounds of basic lipids were separated. Two major unknown compounds A and B and a minor unknown compound C were separated, in addition to minor compounds sphingosine and N,N-dimethylsphingosine. This paper describes the isolation and chemical characterization of major unknown compounds A and B, which were found only in the white matter but not in the gray matter of the human brain. Unmodified psychosine (galactosylsphingosine) was essentially undetectable under the experimental conditions. Unknown compounds A and B were identified as novel plasmal (fatty aldehyde) conjugates of psychosine with cyclic acetal linkage at the galactosyl residue of psychosine. Fatty aldehydes were identified as mainly palmital (16:0) and stearal (18:0). Sphingosine was identified as d18:1 sphingosine. Faster migrating compound A had 3,4-cyclic acetal linkage, and slower migrating compound B had 4,6-cyclic acetal linkage (where m is 14 or 16 and n is 12) as shown below. [formula: see text] Preliminary studies showed that compounds A, B, and C had a weak inhibitory effect on protein kinase C (PKC) and had no cytotoxic effect. In contrast, psychosine displayed a strong cytotoxicity and inhibitory effect on PKC. Therefore, the process controlling the addition or deletion of plasmal cyclic linkage to psychosine could be a crucial step in regulation of PKC, src, or other kinases susceptible to psychosine.
Nudelman
E D
ED
Biomembrane Institute, Seattle, Washington 98119.
Levery
S B
SB
Igarashi
Y
Y
Hakomori
S
S
D000080:Acetals / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002554:Cerebrosides / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008745:Methylation; D008875:Middle Aged; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011609:Psychosine / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000080:Acetals; D002554:Cerebrosides; D011609:Psychosine; D011493:Protein Kinase C