Comparison of different components in the fractional conversion of mevalonate to cholesterol with cholesterol synthesis and serum methyl sterols

Abstract

Serum squalene and methyl sterols (cholesterol precursors), and the fractional conversion of mevalonate to cholesterol (FCM) were determined after an i.v. injection of a labelled mevalonate-labelled cholesterol mixture in fifteen studies in eleven subjects with varying cholesterol synthesis rates (sterol balance values), including three cases with ileal dysfunction. FCM was divided in two components, FCM I and FCM II, hypothesised to represent rapidly and slowly mixing components of newly formed cholesterol, respectively. Cholesterol synthesis ranged from 1.42 to 8.75 mmol day⁻¹ and FCM from 0.352 to 0.857. The synthesis ratewas correlated with FCM, with FCM II, weakly or not at all with FCM I, highly significantly with serum methyl sterolsand insignificantly with serum squalene. However, within the fairly narrow normal synthesis limits (<3.3 mmol day⁻¹) the synthesis rate was not correlated significantly with FCM. Despite a marked range of obesity and a highly significant correlation between the synthesis and body weight only FCM II was correlated with body weight in subjects without ileal dysfunction. The findings suggest that FCM, and its components FCM I and FCM II reflect weakly the total cholesterol synthesis rate, and the rapidly and slowly mixing portions of newly formed cholesterol, respectively.

Key Words:

• cholesterol synthesis
• fecal steroids
• ileal dysfunction
• lanosterol
• mevalonate
• obesity
• oxandrolone
• squalene
• sterol balance