TY - JOUR
T1 - Autoxidation of cysteine generates hydrogen peroxide
T2 - Cytotoxicity and attenuation by pyruvate
AU - Nath, Karl A.
AU - Salahudeen, Abdulla K.
PY - 1993
Y1 - 1993
N2 - The reactivity of cys-teine presents a paradox: although regarded as an antioxidant, cysteine interacts with oxygen in a metal-catalyzed reaction to produce reactive species. Because ischemia provokes the appearance of millimolar amounts of cysteine and increased amounts of transition metals, we studied whether cysteine, in the presence of transition metals, consumes oxygen, generates hydrogen peroxide, and is toxic. Using fluorescence cytometry, we provide direct evidence that hydrogen peroxide is copiously generated during cysteine autoxidation. Pyruvate attenuates such generation of hydrogen peroxide and cytotoxicity. Cysteine oxidation is stimulated by an EDTA-chelatable diethyldithiocarbamate-chelatable constituent of kidney extract; this suggests that copper is the catalytically active metal. The toxicity resulting from cysteine oxidation is less than that induced by amounts of reagent hydrogen peroxide that produce comparable fluorescence. Cysteine also prevents hydrogen peroxide-induced toxicity. Thus, although cysteine generates hydrogen peroxide, it can guard against hydrogen peroxide toxicity, possibly by binding metals on which the toxicity of hydrogen peroxide is dependent. Thus the behavior of cysteine can be salutary or pernicious; the net effect of cysteine, within this wide ambit of actions, is decisively influenced by the conditions to which cysteine is exposed.
AB - The reactivity of cys-teine presents a paradox: although regarded as an antioxidant, cysteine interacts with oxygen in a metal-catalyzed reaction to produce reactive species. Because ischemia provokes the appearance of millimolar amounts of cysteine and increased amounts of transition metals, we studied whether cysteine, in the presence of transition metals, consumes oxygen, generates hydrogen peroxide, and is toxic. Using fluorescence cytometry, we provide direct evidence that hydrogen peroxide is copiously generated during cysteine autoxidation. Pyruvate attenuates such generation of hydrogen peroxide and cytotoxicity. Cysteine oxidation is stimulated by an EDTA-chelatable diethyldithiocarbamate-chelatable constituent of kidney extract; this suggests that copper is the catalytically active metal. The toxicity resulting from cysteine oxidation is less than that induced by amounts of reagent hydrogen peroxide that produce comparable fluorescence. Cysteine also prevents hydrogen peroxide-induced toxicity. Thus, although cysteine generates hydrogen peroxide, it can guard against hydrogen peroxide toxicity, possibly by binding metals on which the toxicity of hydrogen peroxide is dependent. Thus the behavior of cysteine can be salutary or pernicious; the net effect of cysteine, within this wide ambit of actions, is decisively influenced by the conditions to which cysteine is exposed.
KW - Antioxidants
KW - Autoxidation
KW - Copper
KW - Ischemia
KW - Thiols
KW - α-keto acids
UR - http://www.scopus.com/inward/record.url?scp=0027461450&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027461450&partnerID=8YFLogxK
M3 - Article
C2 - 8447440
AN - SCOPUS:0027461450
SN - 0363-6127
VL - 264
SP - F306-F314
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
IS - 2 33-2
ER -