Aldose reductase: an aldehyde scavenging enzyme in the intraneuronal metabolism of norepinephrine in human sympathetic ganglia.
The neurotransmitter norepinephrine is metabolized by monoamine oxidase into an aldehyde intermediate that is further metabolized to the stable glycol derivative, 3,4-dihydroxyphenylglycol (DHPG). In this study, the possible role of aldose reductase in reducing this aldehyde intermediate in human sympathetic neurons has been examined. DHPG is formed when norepinephrine is incubated with aldose reductase in the presence of monoamine oxidase. DHPG metabolism is inhibited by the monoamine oxidase inhibitor, pargyline which prevents the deamination of norepinephrine, and by the aldose reductase inhibitor AL 1576, which inhibits DHPG formation without affecting the deamination of norepinephrine. Although similar formation of DHPG was observed with human liver aldehyde reductase, the production of DHPG was more effective with aldose reductase than aldehyde reductase. Two peaks of reductase activity corresponding to aldose reductase and aldehyde reductase were observed when sympathetic ganglia were chromatofocused. Molecular modeling studies indicate that the energy-minimized structure of 3,4-dihydroxymandelaldehyde bound to aldose reductase is similar to that of glyceraldehyde where the 2'-hydroxyl group forms hydrogen bonds with Trp111 and NADPH. These results suggest that aldose reductase may be important in metabolizing the potentially toxic aldehyde intermediate formed from norepinephrine in human sympathetic ganglia.
Kawamura
Minoru
M
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Eisenhofer
Graeme
G
Kopin
Irwin J
IJ
Kador
Peter F
PF
Lee
Yong S
YS
Fujisawa
Shigeki
S
Sato
Sanai
S
D000310:Adrenal Gland Neoplasms / Q000201:enzymology; D000368:Aged; D000449:Aldehyde Reductase / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000502:physiology; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008676:Metanephrine / Q000031:analogs & derivatives; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000378:metabolism; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010673:Pheochromocytoma / Q000201:enzymology; D013379:Substrate Specificity
D000447:Aldehydes; D008676:Metanephrine; D008734:Methoxyhydroxyphenylglycol; D000449:Aldehyde Reductase; D008995:Monoamine Oxidase; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D004837:Epinephrine