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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-11-8
pubmed:abstractText
It has been proposed that considerable DNA damage may be caused by endogenous metabolites produced during the body's normal metabolic processes. 5-hydroxytryptamine (serotonin) is an important neurotransmitter in brain and spinal cord. We have previously shown that serotonin induces oxidative cleavage of DNA strands in the presence of copper ions. In the present paper we have examined the mechanism of copper binding by serotonin using absorption spectroscopy, Cu(II)-mediated lipid peroxidation and by determining the oxidation of the serotonin molecule. Addition of increasing concentrations of Cu(II) to serotonin leads to a progressive enhancement in the absorption band and is accompanied by a shift towards a lower wavelength indicative of the formation of an oxidised species of serotonin. Studies with the structurally related molecules tryptophan and melatonin showed that only serotonin is able to reduce Cu(II) to Cu(I). Similarly, only serotonin was found to be able to abolish the copper-mediated peroxidation of mitochondria. These results suggested the involvement of the phenolic group in copper binding. Further, it was also shown that the binding of copper to serotonin leads to the formation of a quinone in the absence of molecular oxygen. Based on these results, a model has been proposed in which serotonin reduces two molar equivalents of Cu(II) to Cu(I) through a reaction involving two electron oxidation of the phenolic ring to a quinone methide.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0887-2333
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
669-74
pubmed:dateRevised
2009-4-10
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Serotonin-Cu(II)-mediated DNA cleavage: mechanism of copper binding by serotonin.
pubmed:affiliation
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh (U.P.) 202 002, India.
pubmed:publicationType
Journal Article