Inherited Variants of Human Red Cell Carbonic Anhydrases

Abstract

The present state of knowledge concerning the genetic control of human red cell carbonic anhydrases I and II (CA I and CA II) is reviewed. A total of 25 electrophoretic variants, and one deficiency variant of CA I, and 7 electrophoretic variants of CA II have been discovered after screening a minimum of about 50,000 (CA I) and 39,000 (CA II) individual bloods from a variety of human populations. The amino acid substitution has been determined for 8 of the CA I variants and one of the CA II variants. Three previously undescribed variants of CA I (CA I Montreal-1, CA I Montreal-2, and CA I Montreal-3) and two new variants of CA II (CA II London and CA II Detroit) are reported. Three of the CA I variants (CA I Australia-1, CA I Bombay, and CA I Mindanao), and four of the CA II variants (CA II2, CA II Australia, CA II Bombay, and CA II Baniwa) were observed to occur at frequencies of greater than 1%; however, CA I Bombay, CA I Mindanao, CA II Bombay, and CA II Baniwa appear to be private polymorphisms limited to small populations. None of the electrophoretic variants, or the CA I deficiency variant, even in the homozygous state, appear to be associated with any clinical disorder. A defective form of CA I reported as possibly responsible for an inherited type of renal tubular acidosis has not been characterized sufficiently to exclude the possibility of secondary effects.

Human hypoxanthine-guanine phosphoribosyltransferase. Demonstration of structural variants in lymphoblastoid cells derived from patients with a deficiency of the enzyme.

“…Detailed studies on the structure and function of enzyme variants in man have been limited to the more abundant erythrocyte-or plasma-borne enzymes such as glucose-6-phosphate dehydrogenase (1), phosphoglycerate kinase (2), and carbonic anhydrase (3). Similar studies on mutant forms of the many other less abundant human intracellular enzymes have been unsuccessful because of the extreme difficulty in purifying the products of the mutant alleles in quantities necessary for detailed analyses.…”

Polymorphic gene for human carbonic anhydrase II: a molecular disease marker located on chromosome 8.

“…So far, in human tissues and cells, CA I has been detected primarily in erythrocytes, CA II in a wide variety of tissues, CA III mainly in red skeletal muscle, and CA IV in lung (4,5,7). Several electrophoretic variants of human ervthrocyte CA I and CA II have been described, some of which occur at polymorphic frequencies (10). An electrophoretically silent variant of human skeletal muscle CA III has recentlv been reported to occur at high frequencies in both Black and White populations (11).…”

Effect of Metabolic Acidosis on Hydrogen Ion Excretion in a Pigtail Macaque with Erythrocyte Carbonic Anhydrase I Deficiency

“…Furthermore, we have recently reex- amined one of the individuals with RTA and an inactive red cell CA I originally reported by Shapira et al (9) and found the levels and activities of her red cell CA I to be within normal limits (23). It is possible that the discrepancies between our findings and those of Shapira et al (9) could be due to the presence or absence of inhibitors resulting from differences in the purification procedures.…”