Biochemistry - The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Organization of Metabolism: Catabolic Pathways
Catabolism of Propionyl-CoA and Propionate

During the $\beta$-oxidation of odd-chain Fatty acids, not only acetyl-CoA but also propionyl-CoA is produced. The three-carbon propionyl group is also formed during The breakdown of isoprenoid compounds, isoleucine, Threonine, and Methionine.

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FIG. 9-5. The Dicarboxylic Acid Cycle, in which glyoxylate is oxidized to carbon dioxide.

Humans consume small amounts of propionic acid, which is found, for example, in Swiss cheese (produced by propionic acid-producing Bacteria during manufacturing); propionate is also added to bread to prevent mold growth. For ruminants, particularly cows¹⁾, propionate serves as one of the primary Energy Sources.

¹⁾ In cattle, sheep, and other ruminants, ingested food undergoes intensive Fermentation in the rumen, a large digestive organ containing Cellulose-degrading bacteria and certain Protozoa. The main End products of rumen fermentation are acetate, propionate, and butyrate.

Box 9-E

Selenium: Deadly Poison and Essential Nutrient

Schwarz and his coworkers discovered a remarkable fact in 1957: the highly toxic element selenium turned out to be an essential dietary component, the absence of which led to rat Liver Cell death^a. As little as 0.1 ppm of selenium in the diet was sufficient to prevent liver necrosis. Approximately similar amounts of selenium were later found to prevent The Development of muscular dystrophy ("white Muscle disease") in cattle and sheep grazing in selenium-deficient areas. Sodium selenite and other inorganic selenium compounds proved more effective in this regard than Organic compounds in which S was replaced by Se.

Recently, four selenium-containing Proteins have been discovered^b,c. Using radioactive ⁷⁵Se, small quantities of these selenoproteins were isolated in pure form. Selenium is likely covalently bound to the protein, possibly to an aromatic or heterocyclic prosthetic group.

One of the selenoproteins, whose function has not yet been established, was isolated from muscle. It is absent in animals with muscular dystrophy. This is a small protein with a Molecular Weight of ~ 10,000, containing a heme prosthetic group.

Another selenium-containing protein is Glutathione peroxidase, which catalyzes The oxidation of glutathione (GSH, Box 7-G) by hydrogen peroxide^c,d:

Unlike most peroxidases, this enzyme is not a hemoprotein, but contains a single selenium atom linked to a peptide chain with a molecular weight of ~ 22,000. The native enzyme is a tetramer composed of four such chains. Glutathione peroxidase is the primary defense mechanism against the accumulation of H₂O₂ and organic peroxides in Cells (Box 10-A).

A third selenoprotein, formate dehydrogenase (described in the main text), contains both selenium and molybdenum.

The function of the fourth selenoprotein, isolated from Clostridium sticklandii, is associated with the reductive deamination of Glycine.

The Mechanism of this remarkable amino acid reduction by a dithiol compound remains an enigma, but among the three or four proteins of this reductase system is a thermostable acidic protein with a molecular weight of ~ 12,000 containing one selenium atom per molecule^b.

Other potential BIOLOGICAL Functions OF selenium have also been considered. A selenoprotein may act as an electron transfer mediator from reduced glutathione to the cytochrome system^e. There are reports of selenium's ability to protect animals against the Toxic effects of mercury—a fact that may be related to the ease with which selenium undergoes methylation (Chap. 8, Sec. M, 7). Numerous data indicate a close interrelationship between the dietary requirements for selenium and vitamin E. Deficiency in either causes muscular dystrophy in many animals and severe edema ("exudative diathesis") in chickens. Since vitamin E-deficient rats also exhibit low selenide (Se^2-) levels, it has been suggested that Vitamin E protects reduced selenium from oxidation^f. Based on these observations, it has also been postulated that proteins containing an Fe—Se center exist, analogous to the well-known Fe—S proteins (formate dehydrogenase from Clostridium thermoaceticum contains both nonheme iron^b and selenium).

Relatively little is known about selenium METABOLISM^b. Using ⁷⁵Se as a tracer, it has been shown that normal rat liver contains Se^2-, SeO^2-₃, and selenium in more oxidized states^b. It is hypothesized that the reduction of selenite to selenide involves glutathione^g. Nonenzymatic reduction of selenite by glutathione leads to The formation of a selenotrisulfide

The latter compound spontaneously decomposes into oxidized glutathione and elemental selenium, or, in the presence of glutathione reductase, into glutathione and selenium. It is highly probable that selenium can be incorporated into organic groups from seleno-persulfide Intermediates of the type postulated in the final reaction.

^a Frieden E., Sci. Am., 227, 52—60 (Jul 1972).

^b Stadtman T. C., Science, 183, 915—922 (1974).

^c Ganther H. E. In: Selenium (R. A. Zingaro and W. C. Cooper, eds.), pp. 546—614, Van Nostrand-Reinhold, Princeton, New Jersey, 1974.

^d Rotruck I. T., Pope A. L., Ganther H. E., Swanson D., Hafeman G., Hoekstra W. G., Science, 179, 588—590 (1973).

^д Levander О. A., Morris V. C., Higgs D. I., Fed. Proc., Fed. Am. Soc. Exp. Biol., 32, 886 (abstr.) (1973).

^е Diplock A. T., Lucy I. A., FEBS Lett., 29, 205—210 (1973).

^ж Sandholm M., Sipponen P., ABB, 155, 120—124 (1973).