Biochimica et Biophysica Acta (BBA) - General Subjects
ReviewOn the mammalian acetone metabolism: from chemistry to clinical implications
Introduction
Most probably the presence of acetone in scientific thinking may be dated from 1798, when an English physician, John Gallo, described a material in human breath of an odor of decaying apples [1]. In 1857, this compound was identified as acetone [1]. At that time, acetone was regarded as a characteristic feature of diabetic coma [1]. By the end of nineteenth century, on the basis of the observations of Schwartz [2] made in dogs and of Geelmuyden [3] made in rabbits, dogs and humans, it was concluded that acetone was not a worth-mentioning intermediate of metabolism. The above findings were corroborated by the experiments of Koehler et al., who after having reinvestigated the fate of acetone in humans came to the same conclusion, namely, acetone was poorly, if at all, utilized [4].
For a long time, acetone was regarded as a waste product of metabolism. This flat opinion on its role in metabolism started changing in the second third of twentieth century, when radioactive compounds were initiated in biochemical research. Since the end of 1940s, experimental data became available showing that 14C-carbons of labelled acetone were found in cholesterol, fatty acids, urea and glycogen, thus opposing the dogma that mammals were unable to metabolize acetone to intermediates of metabolism in a substantial degree [5], [6], [7], [8], [9]. Extensive oxidation of acetone to carbon dioxide exhaled in respiratory air was also recognized [6], [9], [10]. The possibility of in vivo formation of glucose from acetone in experimental animals was also published by several groups [9], [10], [11], [12], [13], [14], [15]. In vitro glucose formation from acetone was detected in isolated rat and murine hepatocytes [16], [17], but not in perfused rat liver [18]. Accordingly, 2-14C-acetone was reported to incorporate into glucose in fasting and diabetic humans [19], [20].
In the mid-1980s, two papers appeared trying to give an overview of the metabolic pathways of acetone metabolism [21], [22]. At that time, acetone research was brought into the focus and lived its second golden age, but since the 1990s, the interest has shown a tendency to decrease. This trend becomes obvious if somebody takes into consideration the number of papers published in this field. This paper reviews the chemistry of acetone in brief, the studies of acetone metabolism mostly in mammals, both in vivo and in vitro, and the toxicity of acetone. Attention is also paid to the possible physiological roles of acetone metabolism in humans and to the roles of acetone in disease processes.
Section snippets
Chemistry of acetone
Acetone (2-propanone, dimethyl ketone, β-keto-propane, pyroacetic ether) is a volatile, highly flammable liquid with a characteristic odor.
Acetone metabolism in mammals
At the end of nineteenth century, it was Schwartz, who demonstrated that less portion of administered acetone was recovered in the breath of dogs when the dose was lowered, thus raising the possibility of acetone metabolism at a very low rate if added in a small amount [2]. Later extensive studies were undertaken mostly with rats.
After administration of 2-14C-acetone or 1, 3-14C-acetone to rats by stomach tube or by injection, the examination of animal carcasses led to a demonstrable amount of
Acetone metabolism in vitro
Using liver homogenates, Rudney [46] and Coleman [44] detected 1,2-propanediol and lactate formation from 2-14C-acetone, respectively. In contrast, the first papers upon its in vitro metabolism in rat liver slices led to the conclusion that liver was able to convert acetone into metabolically active C2 fragments finally resulting in acetate formation [5], [8].
Casazza et al. [16] prepared hepatocytes from male rats maintained on 1% acetone drinking water for 5–6 days and starved for 48 h before
Production of acetone
There are two sources of acetone production: the decarboxylation of acetoacetate and the dehydrogenation of isopropanol. The former compound seems to be the major source of acetone in mammals and arises from either lipolysis or amino acid degradation.
Clinical implications
For etiological reasons, acetonemiae are classified as of endogenous and exogenous origin. An acetonemia is referred to as endogenous when the reason of why plasma level of acetone increases is due to a metabolic disturbance related to a disease or to physical exercise (Table 2). In all other cases, acetonemia is considered of exogenous origin regardless of whether the cause of the rise of plasma acetone concentration is the intake of an acetone precursor (e.g. isopropanol) or acetone itself,
Conclusions
Even in 1980, Robinson and Williamson [163] wrote in their work on ketone bodies, that “we make no mention of acetone, which is formed by non-enzymatic breakdown of acetoacetate and is unlikely to be important in metabolism of the intact animal”. Since then, lots happened in this field and in present days, it is beyond doubt that acetone is a normal constituent of metabolism and cannot be regarded as a waste product of metabolism [21], [22]. However, there are two sets of problems that we face.
Acknowledgements
At that time when the experiments were undertaken by the author and his coworkers, the financial support was provided by the Ministry of Welfare (Budapest, Hungary). Herewith, the author acknowledges Ms. Gizella Ferencz, Ms. Anikó Lakatos, Mr. Tamás Gábler and Mr. Antal Holly for their participation in the technical part of the experiments. Dr. Gábor Bánhegyi, Dr. Ferenc Antoni, Tamás Garzó, Dr. József Mandl and Dr. Pál Riba are acknowledged for their valuable participation in discussions when
References (173)
- et al.
J. Biol. Chem.
(1941) - et al.
J. Biol. Chem.
(1949) J. Biol. Chem.
(1950)- et al.
J. Biol. Chem.
(1951) - et al.
J. Biol. Chem.
(1986) - et al.
J. Biol. Chem.
(1986) - et al.
J. Biol. Chem.
(1984) - et al.
Int. J. Biochem.
(1994) - et al.
J. Biol. Chem.
(1987) Trends Biochem. Sci.
(1986)
Trends Biochem. Sci.
J. Biol. Chem.
J. Biol. Chem.
J. Biol. Chem.
Lancet ii
J. Chromatogr.
Clin. Chim. Acta
Biochem. Pharmacol.
J. Chromatogr.
Arch. Biochem. Biophys.
Anal. Biochem.
J. Biol. Chem.
J. Nutr.
Int. J. Biochem. Cell Biol.
Clin. Chim. Acta
Clin. Chim. Acta
Life Sci.
J. Biol. Chem.
Jpn. J. Pharmacol.
Toxicol. Appl. Pharmacol.
J. Biol. Chem.
Toxicol. Appl. Pharmacol.
Int. Hepatol. Commun.
Biochem. Biophys. Res. Commun.
Biochem. Pharmacol.
J. Biol. Chem.
Med. Hypotheses
Biochim. Biophys. Acta
Trans. Am. Clin. Climatol. Assoc.
Arch. Exp. Pathol. Pharmakol.
Z. Physiol. Chem.
J. Biol. Chem.
J. Biol. Chem.
Am. J. Physiol.
Am. J. Physiol.
Biochem. J.
Horm. Metab. Res.
Diabetes
J. Clin. Invest.
Chem. Eng. News
Cited by (176)
Application of metal-organic frameworks for sensing of VOCs and other volatile biomarkers
2024, Coordination Chemistry ReviewsNMR analysis seeking for cognitive decline and dementia metabolic markers in plasma from aged individuals.
2024, Journal of Pharmaceutical and Biomedical AnalysisProfiling of exhaled volatile organics in the screening scenario of a COVID-19 test center
2022, iScienceCitation Excerpt :As SARS-CoV-2 infection causes dysbiosis of intestinal flora and disrupts gut barrier integrity leading toward leaky gut (Giron et al., 2021; Hussain et al., 2021), it is likely to reduce upstream production of crotonaldehyde but to increase uptake of glucose. Consequently, the exhalation of the putative biproduct of hepatic and cellular glycolysis, i.e. acetone (Kalapos, 2003), increased significantly in the SARS-CoV-2-infected individuals, while compared to the healthy subjects. In line with our findings, elevated breath acetone concentrations in COVID-19 patients are also reported in a recent study (Ruszkiewicz et al., 2020).
Monitoring rapid metabolic changes in health and type-1 diabetes with breath acetone sensors
2022, Sensors and Actuators B: ChemicalFlame-made chemoresistive gas sensors and devices
2022, Progress in Energy and Combustion Science