High cerebroside sulfotransferase activity in a hereditary demyelinating neuropathy

'Trembler', a spontaneous, dominantly-inherited murine mutation causes spastic paralysis and an action tremor in mice. Peripheral nerves of Trembler mice show recurrent demyelination, remyelination and onion bulb formation resembling findings reported for onion bulb neuropathies in man. The metabolism of sulfatide, a lipid enriched in myelin, was investigated in this mutation. The sulfatide content of the nerve was decreased in Trembler mice but reflected the low myelin content. The specific activity of cerebroside sulfotransferase (CST), the enzyme responsible for the transfer of sulfate to cerebroside to form sulfatide, was increased by 257 percent in 15-day-old mutants. No activator or inhibitor effect and no lack of product inhibition could explain these results. In mutant PNS, Km, Vmax and heat sensitivity values for CST differed from controls In contrast, no abnormality could be demonstrated in mutant brain. These results suggest the presence of an abnormal enzyme, with a decreased affinity for its substrate but present in larger amounts. In vivo incorporation of radioactive sulfate into sulfatide and nonlipidic material was increased. The lack of accumulation of sulfatides could be explained by the low levels of substrate available and high arylsulfatase A activities. High arylsulfatase A activities with normal CST activities were observed in demyelinating diseases.