Effect of regulating cholesterol biosynthesis on breath isoprene excretion in men.
Isoprene is a normal constituent of human breath and may be derived from the cholesterol synthetic pathway. Acute and chronic lovastatin and a cholesterol-supplemented diet were used to determine whether a mechanistic link exists between isoprene and cholesterol biosynthesis in vivo in humans. The acute effects of lovastatin, a competitive inhibitor of the rate-limiting step of cholesterol biosynthesis, on breath isoprene excretion was determined by administering a single 20, 40 or 80 mg dose of this drug to five healthy male subjects at 8 p.m. and measuring their breath isoprene levels every 4 h for one 24 h cycle before and after treatment. When compared to the baseline cycle, all three doses of lovastatin significantly reduced breath isoprene levels at 6 and 10 h post-drug treatment. Chronic lovastatin therapy (40 mg b.i.d. for 6 wk) reduced 6 a.m. breath isoprene levels (time of maximum baseline value) by 27 +/- 9% (SEM) and cholesterol synthesis measured in freshly isolated mononuclear leukocytes (ML) by 12 +/- 6%. A cholesterol-supplemented diet (1070 mg, total) ingested for 6 wk reduced breath isoprene excretion and ML sterol synthesis by 16 +/- 5 and 19 +/- 4%, respectively. The parallel decreases in isoprene excretion and cholesterol synthesis caused by these pharmacologic and dietary means suggest that breath isoprene is derived from the cholesterol synthesis pathway.
Department of Medicine, University of Minnesota, Minneapolis.
B G
BG
Stone
T J
TJ
Besse
W C
WC
Duane
C D
CD
Evans
E G
EG
DeMaster
D000293:Adolescent; D000328:Adult; D002070:Butadienes / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D045782:Hemiterpenes; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008148:Lovastatin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010420:Pentanes; D012119:Respiration / Q000502:physiology*
D002070:Butadienes; D002791:Cholesterol, Dietary; D045782:Hemiterpenes; D010420:Pentanes; C005059:isoprene; D002784:Cholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases