The metabolic behavior of a heavy chain disease protein (γ HCD-JM) has been investigated in four patients with normal IgG levels, in the heavy chain disease patient himself, in a patient with a G-myeloma protein and in a patient with myotonic dystrophy. The protein was isolated from urine, labeled with 131I and administered once to each of the patients. The γ HCD-JM belongs to the G3 subclass of IgG and its catabolic behavior is like that of intact proteins of the same G3 subclass. The survival

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... half time of 6.6 days and the fractional catabolic rate of 39.5% per day is similar to that of intact G3 immunoglobulins. The γ HCD-JM resembles pooled normal IgG (predominantly composed of IgG1 molecules) in several other catabolic properties. Thirty-nine per cent is distributed in the intravascular pool, as compared with 44% for normal IgG. The survival half time and fractional catabolic rate of this protein is altered by the serum IgG level. Subjects with hypercatabolism of IgG associated with myotonic dystrophy or with high serum levels of IgG (multiple myeloma) also have shortened γ HCD survival and high fractional catabolic rate (FCR). The proteinuric rate is low, like that of IgG. Two per cent of the intravascular pool is lost as proteinuria daily. These findings support the concept that the Fc portion of the IgG molecule determines the catabolic rate of IgG. Studies of the metabolism of the γ HCD-JM in the heavy chain disease patient himself show that the FCR is slightly elevated and the synthetic rate is high (0.42 g/kg/day compared to mean IgG synthesis of 0.034 g/kg/day in normal individuals). This indicates that the accumulation of H-chain in patients with heavy chain disease does not arise from defective catabolism of the protein but is due to excessive synthesis.