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.
Stone
B G
BG
Department of Medicine, University of Minnesota, Minneapolis.
Besse
T J
TJ
Duane
W C
WC
Evans
C D
CD
DeMaster
E G
EG
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