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

Enzymes: Cellular Protein Catalysts
Specificity of Enzyme Action

One of the most remarkable METABOLISM/8.html">Properties of Enzymes is their high Specificity. In some cases, substrate specificity is virtually absolute. For many years, it was believed that urea was the sole substrate for the enzyme urease, and succinate was the only substrate for succinate dehydrogenase. Even after extensive search, only one or two compounds with a very similar Structure were found to be acted upon by these enzymes:

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In other cases, Enzymes exhibit specificity toward a particular class of compounds. For example, renal D-Amino Acid Oxidase catalyzes The oxidation of a wide range of D-Amino Acids but has no effect on L-amino acids.

Equally remarkable is the specificity of enzymes toward a particular type of reaction. Quite often, substrate transformations can proceed along different pathways. An enzyme catalyzes only one pathway, having virtually no effect on alternative reactions. Comparing an enzymatic reaction with an uncatalyzed organic reaction, one is struck by the fact that while the latter yields a large amount of by-products, the enzymatic reaction proceeds in an exceptionally "clean" manner.

Box 6-B

Urease and Trace Amounts of Nickel

In addition to its previously noted virtually absolute specificity toward its substrate (urea), urease isolated from jack beans is also remarkable for being the first enzyme to be crystallized. This was achieved in 1926 by J. Sumner. Although Sumner was later awarded the Nobel Prize for this achievement, his initial reports were met with considerable skepticism.

Urease catalyzes the hydrolytic Cleavage of urea to form two molecules of ammonia and one molecule of carbon dioxide, and can be used for the analytical determination of urea. Recently, it was shown that two nickel atoms are associated with each urease molecule (mol. wt. 105,000) ^a-^b. The presence of a metal ion in the urease molecule had not been previously detected, although it was suggested by a "tail" extending into the visible region in the absorption spectrum of the purified enzyme, with a shoulder at 425 nm and small maxima at 725 and 1060 nm.

According to recent data, nickel is essential for animals^c. Thus, on a nickel-deficient diet, chicks grew poorly and had thickened legs; they also exhibited dermatitis. Swollen Cell/35.html">Mitochondria and an expanded perinuclear space were found in the Tissues of such animals, indicating impaired membrane function. The toxicity of nickel is very low, and homeostatic mechanisms exist in the animal body to regulate its concentration. The content of this element in tissues ranges from 1 to 5 µg∙L-1. In serum, nickel is present in low-molecular-weight complexes and is also bound to serum albumin. In addition, a specific nickel-containing protein of the macroglobulin class, named nickeloplasmin, is known^d. Nickel is present in plants, and certain species accumulate it in large amounts^e. Due to the ubiquitous nature of nickel, it is quite difficult to formulate a diet completely devoid of this element.

Although nickel can exist in various oxidation states, the most common is Ni(II). This ion contains eight 3d electrons, and therefore its coordination number is four, with the ligands arranged in a square planar geometry. However, the Ni²⁺ ion is "ambivalent": it is capable of forming a six-Ligand complex with an octahedral structure. It is assumed that the ambivalence of the Ni²⁺ ion has biochemical significance. The exact role of the Ni²⁺ ion in urease function has not been established, but it is possible that it participates in the catalytic process, similar to the Zn²⁺ ion in carboxypeptidase (Fig. 7-3). It is also possible that the Ni²⁺ ion forms a coordination compound with NH₃, a product of substrate cleavage. It has been suggested that nickel ions or those of some other transition metals are also contained in several Other Enzymes that catalyze the Hydrolysis of glutamine to form ammonia (Ch. 14, Sec. B, 2)⁶.

^a Dixon N. E., Gazzola C., Blakeley R. L., Zerner B. (1975). J. Amer. Chem. Soc., 97, 4131—4133.

^b Dixon N. E., Gazzola C., Blakeley R. L., Zerner B. (1976). Science, 191, 1144—1150.

^c Nielson F. H. (1974). In: Trace element metabolism in animals-2 (W. G. Hoekstra, J. W. Suttie, H. E. Ganther and W. Mertz, eds.), pp. 381—395. University Park Press, Baltimore, Maryland; see also Schnegg A., Kirchgessner M. (1976). Int. J. Vitamins Nutr. Res., 46, 96—99.

^d Nomoto S., McNeely M. D., Sunderman F. W., Jr. (1971). Biochemistry, 10, 1647—1651.

^e Severne B. C. (1974). Nature (London), 248, 807—808.