Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews and correlates three separate recent findings that implicate the one-carbon cycle in neuropsychiatric disease: (i) the demonstration by kinetic studies that the Vmax of methionine adenosine transferase (MAT) is reduced in some schizophrenics and depressives and is increased in some manics, and that the activity of serine hydroxymethyltransferase (SHMT) is reduced in a further subpopulation of schizophrenics; (ii) the demonstration that S-adenosylmethionine (the product of MAT) is an effective clinical antidepressant; and (iii) the reports that L-methionine is an effective treatment for certain of the symptoms of Parkinson's disease. These clinical findings may be correlated with recent findings that transmethylation reactions (lipid and carboxymethylation) play an important role in synaptic events (coupling of receptors to adenylate cyclase and release of neurotransmitters).
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PMID:The role of the one-carbon cycle in neuropsychiatric disease. 632 30

The vitamin B(6)-derived pyridoxal 5'-phosphate (PLP) is the cofactor of enzymes catalyzing a large variety of chemical reactions mainly involved in amino acid metabolism. These enzymes have been divided in five families and fold types on the basis of evolutionary relationships and protein structural organization. Almost 1.5% of all genes in prokaryotes code for PLP-dependent enzymes, whereas the percentage is substantially lower in eukaryotes. Although about 4% of enzyme-catalyzed reactions catalogued by the Enzyme Commission are PLP-dependent, only a few enzymes are targets of approved drugs and about twenty are recognised as potential targets for drugs or herbicides. PLP-dependent enzymes for which there are already commercially available drugs are DOPA decarboxylase (involved in the Parkinson disease), GABA aminotransferase (epilepsy), serine hydroxymethyltransferase (tumors and malaria), ornithine decarboxylase (African sleeping sickness and, potentially, tumors), alanine racemase (antibacterial agents), and human cytosolic branched-chain aminotransferase (pathological states associated to the GABA/glutamate equilibrium concentrations). Within each family or metabolic pathway, the enzymes for which drugs have been already approved for clinical use are discussed first, reporting the enzyme structure, the catalytic mechanism, the mechanism of enzyme inactivation or modulation by substrate-like or transition state-like drugs, and on-going research for increasing specificity and decreasing side-effects. Then, PLP-dependent enzymes that have been recently characterized and proposed as drug targets are reported. Finally, the relevance of recent genomic analysis of PLP-dependent enzymes for the selection of drug targets is discussed.
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PMID:Pyridoxal 5'-phosphate enzymes as targets for therapeutic agents. 1750 14

L-threo-3,4-Dihydroxyphenylserine (DOPS) is a chiral unnatural beta-hydroxy amino acid used for the treatment of Parkinson disease. We developed a continuous bioconversion system for DOPS production that uses whole-cell biocatalyst of recombinant Escherichia coli expressing L-threonine aldolase (L-TA) genes cloned from Streptomyces avelmitilis MA-4680. Maximum conversion rates were observed at 2 M glycine, 145 mM 3,4-dihydroxybenzaldehyde, 0.75% Triton-X, 5 g E. coli cells/l, pH 6.5 and 10 degrees C. In the optimized condition, overall productivity was 8 g/l, which represents 40 times the synthesis yield possible with no optimization of conditions.
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PMID:Enhanced synthesis of L-threo-3,4-dihydroxyphenylserine by high-density whole-cell biocatalyst of recombinant L-threonine aldolase from Streptomyces avelmitilis. 1903 30