Decreased tyrosine transport in fibroblasts from schizophrenics: implications for membrane pathology.
Two independent studies reported recently have shown a significant decrease in Vmax of tyrosine transport in fibroblasts grown from schizophrenics' skin compared with controls. It has also been shown that tyrosine transport into the brain is decreased in schizophrenics compared with controls. In view of the importance of these findings in elucidating the biochemical mechanism(s) associated with schizophrenia, we have studied the kinetics of tyrosine transport and the levels of monoamine oxidase (MAO) activity in fibroblasts grown from the skins of schizophrenics and unrelated control subjects. Using the Lineweaver-Burk plot, the Eadie Hostee plot and the Hanes plot we have calculated the Km and Vmax for tyrosine transport. We have found a significant decrease in the Km and Vmax values for tyrosine transport in schizophrenics compared with control fibroblast samples. No changes were observed in the levels of MAO. Using Lineweaver-Burk plot (1/S Versus 1/V) it has been shown that the tyrosine transport inhibition is uncompetitive. This finding proposes that the inhibition is in the substrate transport protein complex, which may be taking place during the transit of the substrate through the cell membrane. From the observed findings and from the literature evidence we suggest that the altered metabolism of phospholipids in schizophrenics, such as deficiency of arachidonic acid and docosahexaenoic acid, may be contributing to this observed phenomena.
Ramchand
C N
CN
Department of Psychiatry, Northern General Hospital, University of Sheffield, UK.
Peet
M
M
Clark
A E
AE
Gliddon
A E
AE
Hemmings
G P
GP
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism*
D014443:Tyrosine; D008995:Monoamine Oxidase