Acetone body

Under metabolic conditions associated with a high rate of fatty acid oxidation, the liver produces considerable quantities of acetoacetate and d(—)-3-liydroxyl)utyrate (P-hydroxybutyrate). Acetoacetate continually undergoes spontaneous decarboxylation to yield acetone. These three substances are collectively known as the ketone bodies (also called acetone bodies or [incorrectly ] ketones ) (Figure 22-5). Acetoacetate and 3-hydroxybu-... 

It may be stated at this point that the presence of a /3-hydroxy-butyrate fat in certain organisms is a matter of general biochemical importance. Usually /3-hydroxybutyric acid and the acetone bodies are derived from n-butyric acid directly. The unambiguous formation of jS-hydroxybutyric acid anhydrides from carbohydrates opens up new vistas its formation from acetaldehyde, and from pyruvic acid, through aldol intermediates can be understood without difficulty. Kirrmann s reaction, to which little attention has been paid, is at the same time an example of an oxygen shift, leading from hydroxyaldehydes to fatty acids. 

Knodt, C. B., Shaw, J. C. and White. G. C. 1942. Studies on ketosis in dairy cattle. II. Blood and urinary acetone bodies of dairy cattle in relation to parturition, lactation, gestation and breed. J. Dairy Sci. 25, 851-860. 

A. The mechanism of toxicity is not well understood. Metaldehyde, like paraldehyde, is a polymer of acetaldehyde, and depolymerization to form acetaldehyde may account for some of its toxic effects. Further metabolism to acetone bodies may contribute to metabolic acidosis. 

These changes in GSH level, observed in both human and experimental diabetes, could be the result of (a) a diminished rate of GSH synthesis (b) the interaction of acetone bodies and GSH or (c) the secondary conse-cjuence of the electrolyte abnormalities associated with diabetic acidosis. 

Although GSH reacts with acetone at pH 7.4 (131, 132) it is not known whether this interaction accounts for the fall in the blood GSH observed following the injection of acetone bodies (29). Since ketosis is an accompaniment of severe insulin deficiency and since the observed fall in blood GSH level in human diabetes is correlated with ketosis, it is more probable that the ketosis as well as the decreased rate of GSH synthesis contribute to the lowering of the GSH values. The correction of the diabetic metabolic defect with insulin would not only diminish the ketosis but it would restore the rate of GSH synthesis. 

Coon studied the conversion of carboxyl, j3-carbon, and methyl-labeled isovalerate to acetone bodies. As had been found by previous workers, the carboxyl labeling yielded acetoacetate with tracer in the carboxyl and carbonyl carbons. This is in agreement with reactions 3 and 4 of Fig. 5. It is interesting that the ratios of carboxyl to carbonyl radioactivity in the acetoacetate was higher than unity. This parallels the situation found with the 2-carbon unit arising from the first 2-carbons of straight-chain fatty acids. 

Upon incubation of 2-methyl-C -butyrate, about 4% of the radioactivity appeared in the respiratory CO2 and about an equal amount in the acetone bodies. The major portion of the label was contained in propionate. This was isolated by the carrier technique and the identity of the compound demonstrated by conversion to the p-bromophenacyl ester. No labeled propionate is formed from the corresponding 2-methylbuty-rate-3-C ... 

Propan-2-on, 2-Propanon, Dimethylketon ketone body (acetone body)... 

Study of the conversion of the carboxyl, /8-carbon, and methyl-labeled isovalerate to acetone bodies produced the following results. 

Isopropyl alcohol is also employed widely as a solvent for cosmetics (qv), eg, lotions, perfumes, shampoos, skin cleansers, nail poHshes, makeup removers, deodorants, body oils, and skin lotions. In cosmetic appHcations, the acetone-like odor of isopropyl alcohol is masked by the addition of fragrance (144). 

Latentiation of ampicillin can also be achieved by tying up the proximate amino and amide functions as an acetone aminal. Inclusion of acetone in the reaction mixture allows 6-APA to be condensed directly with the acid chloride from 24. There is thus obtained directly the prodrug hetacillin (34). Although this compound has little antibiotic activity in its own right, it hydrolyzes to ampicillin in the body. The p-hydroxy derivative amoxycillin (35) shows somewhat better oral activity. A similar sequence using formaldehyde gives metampicillin (36). °... 

Mehrling and Welde first determined if hydro-aromatic ring aldehydes in general gave violet like odours when condensed with acetone, and it was found that in the case of the four following aldehydes only the first yields a body having a violet odour —... 

If the a-phellandrene nitrite be heated with an alcoholic solution of potash, it is converted into nitrophellandrene, Ck,Hi5(N02). This bodyis converted by reduction with sodium and alcohol into tetrahydrocarvone, or by less energetic reduction with zinc and acetic acid, into carvotan-acetone. The relationship between these bodies is shown by the following formulas —... 

The residue of the ether solution is fractionally distilled under a reduced pressure and the fraction is collected, which boils under a pres-sure of 12 mm. at a temperature of from 138° to 155° C., and from it the unattacked citral and unchanged acetone and volatile products of condensation are separated in a current of steam, which readily carries off these bodies. 

This ketone, of the formula Cj H O, isomeric with those above described, is found in the oils of thuja, tansy, wormwood, and sage. It is identical with the bodies formerly described under the names tan-acetone and salvone. It is best prepared in a state of purity from oil of wormwood. According to Semmler, 200 c.c. of the oil, 0 c.c. of a saturated solution of sodium bisulphite, 75 c.c. of water, and 300 c.c. of alcohol are well shaken at intervals during a fortnight. The crystals formed, consisting of the compound of thujone with the sodium bisulphite, are separated, washed with alcohol-ether, and pressed. On treatment with caustic soda solution, the thujone, amounting to over 40 per cent, of the oil used, separates, and can be distilled with steam. 

Benzylidene acetone, C Hg. CH CH. COCH, is a crystalline body melting at 42°, having an intense floral odour. It restilts from the condensation of benzaldehyde and acetone under the influence of caustic soda. It has the following characters —... 

Normally, only small amounts of acetone are produced in the human body. Diabetics produce larger amounts, sometimes enough to give their breath a sweet odor. 

Figure 15-3. Overview of fatty acid metabolism showing the major pathways and end products. Ketone bodies comprise the substances acetoacetate, 3-hy-droxybutyrate, and acetone.

In the liver, it forms ketone bodies (acetone, ace-toacetate, and 3-hydroxybutyrate) that are important fuels in prolonged starvation. 

In most cases, ketonemia is due to increased production of ketone bodies by the liver rather than to a deficiency in their utilization by extrahepatic tissues. While acetoacetate and d(—)-3-hydroxybutyrate are readily oxidized by extrahepatic tissues, acetone is difficult to oxidize in vivo and to a large extent is volatilized in the lungs. 

The ketone bodies (acetoacetate, 3-hydroxybutyrate, and acetone) are formed in hepatic mitochondria when there is a high rate of fatty acid oxidation. The pathway of ketogenesis involves synthesis and breakdown of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by two key enzymes, HMG-CoA synthase and HMG-GoA lyase. 

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