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1. Hexosaminidase A of human serum was resolved into two components, a minor form with properties identical with those of the single hexosaminidase A component of human liver, and a major form with significantly different properties. 2. The major serum hexosaminidase A form was eluted from a DEAE-cellulose column at a lower salt concentration than that required to elute the liver form. 3. A multiple-pass technique was used to elute the major serum enzyme A from a Sephadex G-150 column before that of liver enzyme A. 4. Clostridium perfringens neuraminidase converted the major component of serum hexosaminidase A into a form that was held less tightly by DEAE-cellulose, but the minor component of the A enzyme of serum, and the A enzyme of liver were not affected. 5. The hexosaminidase A from tears was similar to the A enzyme from serum, whereas those from several human tissues and from urine and lymph were similar to the liver form. 6. The A enzyme from serum may be derived from the A enzyme from liver by glycosylation before secretion.

Human α-mannosidases A, B and C were partially purified from liver by conventional and affinity chromatographic procedures. The kinetic, physical and immunologic properties of the A, B and C isozymes were determined including pH optima, K(m), effects of various inhibitors and activators, thermal stabilities, electrophoretic mobilities, native molecular weights and antigenic relationships. By gel filtration, the apparent native molecular weights were 240,000, 300,000 and 420,000 for the A, B and C isozymes, respectively. By polyacrylamide gel electrophoresis, the A and B isozymes had native molecular weights of approximately 150,000 and appeared to be charge isomers. Antibodies to the purified A and B isozymes were produced; cross-reactivity between the A and B isozymes against anti-A and anti-B immune sera were observed by double immunodiffusion and immunoprécipitation. In contrast, no reactivity of the C isozyme was detected with either immune serum. Based on these studies, models are presented for the molecular interrelationship of α-mannosidases A and B.

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Females with ornithine transcarbamylase (OTC) deficiency, an X-linked disorder, are mosaic in that they have hepatocytes with almost no enzyme activity and hepatocytes with normal enzyme activity. The normal and abnormal cells occur in clusters since cells in an area tend to be the progeny of the same parent cell. Marked variation in OTC was found in small liver biopsies from a female with OTC deficiency, probably because the samples included clusters of normal or abnormal cells. OTC activity was measured in 10 approx. 5 mg specimens of liver from a single surgical biopsy from a 7 year old girl with OTC def. (two experiments and control autopsy liver (three experiments). The OTC activity in the patient varied 10-40 fold in the two experiments with a coefficient of variation of 76 and 97 percent (control 20.21 and 26 percent). Thus OTC activity in a small biopsy in females with OTC def. may not be representative of the entire liver. The OTC activity in several bits of liver from our patient was very low suggesting that clusters of abnormal cells may often involve a major portion of a hepatic lobule. If so, blood passing through these areas would in effect be passing through a "metabolic shunt'! These shunts may, in part, account for the hyperammonemia in this disorder. The notion that an X-linked disorder can produce disease in heterozygotes by affecting small functional units could apply to other disorders such as nephrogenic diabetes insipidus or vitamin D dependent rickets.

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