Serum aldolase

Dl. Dale, E. A., Demonstration of aldolase in human platelets. The relation to plasma and serum aldolase. Clin. Chim. Acta 5, 652-663 (1960). 

Since the work of Sibley and Fleisher (S22) made it plain that elevation of serum aldolase activity occurred quite characteristically in other diseases besides myopathy, such as in hemolytic anemia and in acute hepatitis, it would be most useful to know that in muscular dystrophy the increased serum aldolase was indeed derived from the diseased muscle. Direct demonstration of this origin has been provided (D14) by showing that in 5 of 10 patients with muscular dystrophy the femoral venous return had a higher serum aldolase activity than the femoral arterial supply to the diseased muscles of the lower limb. Further strong support is given by the discovery that serum contains two aldolases (S8) with different substrate requirements (H5) whereby colorimetric methods have been devised for the separate assay of each (S5). These are 1,6-diphosphofructoaldolase ( muscle aldolase) and 1-phosphofruc-toaldolase ( liver aldolase). The ratio in mammalian tissues of muscle to liver aldolase activity is 40 in skeletal and cardiac muscle, 12-25 in spleen, lung, and red cells, and only unity in liver and kidney (S6, S7). The serum activities of both are equally elevated in hepatitis, but in muscular dystrophy and in muscle crush injury only that of muscle aldolase is raised (S4, S6) indeed, the ratio of serum activity of muscle to liver aldolase has been reported as about unity in healthy individuals and in patients with virus hepatitis, but as about 26 in a series of 14... 

The maintenance within a recognizable range of the serum enzyme activities implies some similarity between their rate of discharge from the tissues into the blood stream and the rapidity of their clearance from it. This clearance can be exceedingly swift, though confronted by skeletal muscle of which 300 mg contains as much aldolase as the entire adult circulation (S22). After the intravenous injection of crystalline aldolase in rats the activity of the serum aldolase rises 7-fold in the first 15 minutes, but 12 hours later has fallen to only 1.5 times the normal value (S24). Further, the intravenous injection in rabbits of pure crystalline aldolase labeled with and the measurement of the rate of disappearance of radioactivity in successive serum specimens indicate... 

Even in normal individuals, however, only moderately strenuous exercise usually causes modest but distinct elevations of the serum activities of aldolase (B6, C5, F3, R3), both transaminases (B6, C5, F3, P12, S21), lactic (B6, C5, F3, T4) and malic (F3) dehydrogenases, and creatine kinase (Al, B6, F2a, R4) which rapidly return to normal after rest, though GPT seems least affected. More sustained military or athletic training programs cause a similar but more persistent rise in these values, but not in that of SGPT (C13, R5). In particular it has been found that serum aldolase activity in untrained subjects rises immediately after 5-10 minutes of exercise, falls to normal shortly afterwards, then rises again briefly from these normal values to fm-ther maxima at 30 minutes and again at 90 minutes after termination of the exercise (R3). It is of in-... 

Diphosphofructoaldolase is a soluble glycolytic enzyme especially abundant in skeletal muscle, occurring also in the myocardium and to a lesser extent in liver and erythrocytes, so that hemolysis of blood specimens elevates the serum aldolase activity and must therefore be avoided. The molecular weight of muscle aldolase is 147,000-180,000 (DIO), Its function is specifically the reversible splitting of D-fructose-1,6-diphosphate (FDP) into equimolecular amounts of the trioses D-glyceralde-hyde-3-phosphate (G-3-P) and dihydroxyacetone phosphate (DAP). 

Throughout the text, serum aldolase has been determined by the spec-trophotometric method (BIO, L7, S29) and both transaminases by the colorimetric method (R2). The normal ranges (R13) in conventional units are for serum aldolase 2.3-8.8 units per ml (mean 5.7 units), for SCOT 12-36 units per ml (mean 19 units), and for SGPT 4-24 units per ml (mean 12 units). In each figure the activity of serum aldolase is denoted by an uninterrupted line, of SCOT by long strokes, and of SGPT by short strokes (Figs. 7-15). 

Condition Age (years) Sex Serum aldolase SCOT SGPT... 

Relationship between serum aldolase activity and age in Duchenne-type dystrophy. 

Thus in muscular dystrophy it is apparent that both the mean elevations of the serum enzyme values and the magnitudes of their variations upon physical activity are proportional to the mass of dystrophic muscle remaining and to the severity of the disease in it. Both are thus greater in early than in evident Duchenne-type dystrophy, less in limb-girdle dystrophy, and least in myotonia congenita. Further, though serum creatine kinase has been found to be an exceedingly delicate index of myopathy (A2, S14), for present purposes serum aldolase is suflBciently... 

Methods have recently been used for measuring arm-to-arm (total) circulation time separately (D6) or simultaneously with arm-tongue (central) circulation time (D5), and abnormal reductions in the difier-ence (peripheral circulation time) predictably found in dystrophic patients (D3) have been found also in female carriers of Duchenne-type dystrophy (D5a, S18) and may be due to increased metabolism of the diseased muscle. By combining these techniques with simultaneous serum aldolase and creatine kinase assay, successful detection of 85-90% of carriers is said to be possible (D7, D7a, D8). Further, electromyographic studies in known carriers have now disclosed the presence of polyphasic responses intermediate in frequency between those found in normal and in dystrophic individuals, thus providing an additional means of discrimination (VI). 

A6. Aronson, S. M., and Volk, B. W., Serum aldolase activity in neuromuscular disorders. II. Experimental application. Proc. Soc. Exptl. Biol. Med. 94, 360 (1957). 

K8. Kitiyakara, A., and Murmanis, 1., Dependence of high serum aldolase on local circulation of injured muscle. Am. /. Physiol. 202, 1059 (1962). 

R14. Rowland, L. F., and Ross, G., Serum aldolase in muscular dystrophies, neuromuscular disorders, and wasting of skeletal muscle. A.M.A. Arch. Neurol. Psychiat. 80, 157 (1958). 

Sibley, J. A., and Fleisher, G. A., The clinical significance of serum aldolase. Proc. Staff Meetings Mayo Clin. 29, 591 (1954). 

Soltan, H. C., and Blanchaer, M. C., Activity of serum aldolase and lactic dehydrogenase in patients affected with Ducherme muscular dystrophy and in their relatives. J. Pediat. 54, 27 (1959). 

Visnapuu LA, Karlson LK, Dubinslreference ranges for serum aldolase. An J Clin Pathol 1989 91 476-7. 

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