Plasma Acetone Metabolism in the Fasting Human

Abstract

A B S T R A C T The metabolism of acetone was studied in lean and obese humans during starvation ketosis. Acetone concentrations in plasma, urine, and breath; and rates of endogenous production, elimination in breath and urine, and in vivo metabolism were determined. There was a direct relationship between plasma acetone turnover (20-77 ,Umol/m2 per min) and concenitration (0.19-1.68 mM). Breath and urinary excretion of acetone accounted for a 2-30% of the endogenous production rate, and in vivo metabolism accounted for the remainder. Plasma acetone oxidation accounted for -60% of the production rate in 3-d fasted subjects and about 25% of the production rate in 21-d fasted subjects. About 1-2% ofthe total CO2 production was derived from plasma acetone oxidation and was not related to the plasma concentration or production rate. Radioactivity from [14C]acetone was not detected in plasma free fatty acids, acetoacetate, ,-hydroxybutyrate, or other anionic compounds, but was present in plasma glucose, lipids, and proteins. If glucose synthesis from acetone is possible in humans, this process could account for 11% of the glucose production rate and 59% of the acetone production rate in 21-d fasted subjects. During maximum acetonemia, acetone productioni from acetoacetate could account for 37% of the anticipated acetoacetate production, which implies that a significant fraction of the latter compound does not undergo immediate terminal oxidation.

Hydroxylation of acetone by ethanol‐ and acetone‐inducible cytochrome P‐450 in liver microsomes and reconstituted membranes

“…The extent of inhibition by imidazole in vitro of the cytochrome P-&O-dependent acetone oxidation correlated well with the findings in vivo regarding the ability of imidazole, at similar concentrations, to prevent the incorporation of ['4C]acetone into low-M, carbohydrates, such as glucose. The apparent J&,, of the reaction in microsomes of about 0.9 mM is lower than the acetone concentrations in plasma reported under starvation and conditions of ketoacidosis [7,8].…”

“…The plasma concentrations of acetone in such subjects are in the range l-10 mM [7,8]. At the smaller acetone concentration, 75% of the acetone produced is metabolized in vivo, especially to glucose [8].…”

Distribution and elimination of 2-[14C]-acetone in mice after inhalation exposure.

“…In our previou·3 study on acetone in man the uptake during 2 h of exposure was 8-16 mg/kg (0.14-0.28 mmol/kg) and the amount exhaled [16][17][18][19][20][21][22][23][24][25][26][27] Ofo of the uptake (21). In this present 3tudy with mice about 52 Ofo of the expired radioactivity after concluded exposure was unmetabolized acetone, and the remaining part carbon dioxide.…”

Acetone Response with Exercise Intensity

“…The acetone concentration correlates with the concentration of blood ß-hydroxybutyrate (Reichard et al 1979;Yamane et al 2006). The kinetic responses of ketone bodies to exercise is very complex.…”

“…Acetone is mainly generated from non-enzymatic, decarboxylation of acetoacetate (Laffel et al 1999;Owen et al 1982). Ketones in blood increased gradually with respect to the length of fasting periods in diabetics and obese people (Tassopoulos et al 1969;Reichard et al 1979). Owen et al (1982) demonstrated that in diabetic patients, plasma acetone concentration is significantly related to breath acetone concentration.…”