The metabolism of malondialdehyde.
Interest in malondialdehyde (MDA) metabolism stems from its formation as a product of lipid peroxidation in the diet and in the tissues; its reactivity with functional groups of nucleic acid bases, proteins and phospholipids; its mutagenicity in bacteria, and its reported skin and liver carcinogenicity in animals. Administration of the Na enol salt of MDA in the drinking water of mice over a range of 0.1-10.0 micrograms/g/day for 12 mo produced dose-dependent hyperplastic and neoplastic changes in liver nuclei and increased mortality at the highest level but produced no gross hepatic tumors. Addition of MDA to the medium of rat skin fibroblasts grown in culture caused nuclear abnormalities at concentrations as low as 10(-6) M despite an uptake of only 4%. [1,3-14C]MDA was rapidly oxidized to [14C]acetate in rat liver mitochondria and to 14CO2 in vivo; however, approximately 10% of the radioactivity was recovered in the urine. Chromatographic analysis of rat urine revealed the presence of several compounds which yield MDA on acid hydrolysis. Total MDA excretion increased in response to conditions which stimulate lipid peroxidation in vivo, including vitamin E deficiency, Fe or CCl4 administration, and enrichment of the tissues with PUFA. N-acetyl-e-(2-propenal)lysine was identified as a major urinary metabolite of MDA in rat and human urine. This compound is derived primarily from N-alpha-(2-propenal)lysine released in digestion as a product of reactions between MDA and the epsilon-amino groups of N-terminal lysine residues in food proteins. However, its presence in the urine of animals fasted or fed MDA-free diets indicates that it is also formed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Draper
H H
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McGirr
L G
LG
Hadley
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D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004032:Diet; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008314:Malonates / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced
D008054:Lipid Peroxides; D008314:Malonates; D008315:Malondialdehyde