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)

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

Putrescine plays a very important role in the regulation of division, differentiation and maturation of cells as well as apoptosis. As the polycationic molecule it stabilizes the structure of DNA and participates in the functioning of cell membranes. It is able to interact with series of ion channels and has affinity for many receptors. The article presents the participation of putrescine in the metabolism of iron and mechanism of its transport across biological membranes. Especially important for the homeostasis of putrescine has ornithine decarboxylase and availability of its substrate--ornithine. Affecting to this enzyme is the simplest and widely used method of controlling the concentration of putrescine. For this purpose its inhibitor-eflornithine is applied. There was also a number of other enzymes involved in the metabolism of putrescine that was presented. Current information about the clinical relevance of putrescine in infertility, embryonic development, hirsutism, epilepsy, Alzheimer's disease, Parkinson's disease, prevention of metastases and hemostasis was also described. These processes were presented, in which putrescine plays a major role and focused on the latest reports. Attention was drawn to the situations where it has beneficial effects and those in which it is the cause of the pathology. Some of the cited reports are in phase of speculation on the possible use of it, but a significant part is already confirmed and used in clinical practice. The facts presented in this article show how great is the meaning of putrescine and how important role this simple specimen plays in the metabolic processes of living organisms.
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PMID:[The importance of putrescine in the human body]. 2486 91