DECREASED TYROSINE TRANSPORT IN FIBROBLASTS FROM SCHIZOPHRENICS - IMPLICATIONS FOR MEMBRANE PATHOLOGY

Two independent studies reported recently have shown a significant dec rease in V-max of tyrosine transport in fibroblasts grown from schizop hrenics' skin compared with controls. It has also been shown that tyro sine transport into the brain is decreased in schizophrenics compared with controls. In view of the importance of these findings in elucidat ing the biochemical mechanism(s) associated with schizophrenia, we hav e studied the kinetics of tyrosine transport and the levels of monoami ne oxidase (MAO) activity in fibroblasts grown from the skins of schiz ophrenics and unrelated control subjects. Using the Lineweaver-Burk pl ot, the Eadie Hostee plot and the Hanes plot we have calculated the K- m and V-max for tyrosine transport. We have found a significant decrea se in the K-m and V-max values for tyrosine transport in schizophrenic s compared with control fibroblast samples. No changes were observed i n the levels of MAO. Using Lineweaver-Burk plot (1/S Versus 1/V) it ha s been shown that the tyrosine transport inhibition is uncompetitive. This finding proposes that the inhibition is in the substrate transpor t protein complex, which may be taking place during the transit of the substrate through the cell membrane. From the observed findings and f rom the literature evidence we suggest that the altered metabolism of phospholipids in schizophrenics, such as deficiency of arachidonic aci d and docosahexaenoic acid, may be contributing to this observed pheno mena.