Investigations of the biological phenomenology and aetiology of schizophreniahave produced a complex pattern which defies unitary theories. It is not surprising that within this framework several com peting theories are equally viable and few can be totally dismissed. One area which has received little attention has been the area of oxidative metabolism (the site of which is the mitochondrion), presumably because it has no obvious association with either the classical pharmacological systems generally assumed to underlie schizophrenic biology or with structural biology. The association of mitochondrial function with human disease has, however, only 35 years after the demonstration of mitochondrial involvement in myopathy, become a rapidly expanding field.Changes in mitochondrial function are now implicated in over 100 diseases, usually associated with mutationsin the mitochondrialgenome. Primary mutation in the mitochondrial genome generally affects tissues with a large energy demand, such as muscle and brain, and result in specific clinical syndromes some of which are discussedin detail below. In addition, however, mitochondrial mutations and impaired oxidative metabolism are also observed associated with some common age-related illnesses, probably as secondaryphenomena. These conditions include the ageing process itself as well as specific centralnervous system disorderssuch as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntingdon's disease. The exact relationship between these mitochondrial changes and these illnesses is still under debate, but this serves to illustrate the growing influence of ideas regarding oxidative phosphorylation in the debate about human disease.In the phenomenology of schizophrenia two main biological clues stand out and yet their exact role remains frustratingly elusive.
The PsMT gene family of pea (Pisum sativum L.) encodes predicted proteins with sequence similarity to metallothioneins. However, PsMT proteins have not yet been characterised in planta and their functions remain obscure. PsMT transcripts were identified in the cortex tissue of pea roots using tissue squash-blotting techniques. Transcripts were not detected on northern blots of RNA isolated from the embryonic radicle, but PsMT transcript abundance in roots increased with age of germinating seedlings. The PsMT A gene was expressed in E. coli as a carboxyterminal extension of glutathione-S-transferase (GST). Fusion protein purified from crude cell lysates (500 mL cultures) bound an estimated amount of 5.99, 6.27 and 7.07 moles of Zn, Cu and Cd respectively per mole protein, compared to equivalent estimates of 0.37, 0.63 and 0.26 moles for GST alone. Similar estimates for Fe-binding were 0.28 moles for GST-PsMT A fusion protein and 0.1 moles for GST alone.In summary, these data: 1, show that PsMT transcripts are abundant in roots of pea plants that have not been exposed to supra-optimal concentrations of trace metals and hence appear to be constitutively expressed and 2, indicate that PsMT A protein can bind certain trace metal ions. We have also identified and partially purified a Zn ligand (Zn-A) and two Cu ligands (Cu-A, Cu-B) from pea roots which have not been exposed to supra-optimal conditions of trace metal ions and are therefore defined as 'constitutive'. Whether or not these ligands include the products of PsMT genes remains to be established.
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