부산대학교 도서관

Inherited deficiency of human phosphofructokinase, an enzyme which catalyzes the key regulatory step in glycolysis, results in a heterogeneous group of diseases characterized by myopathy and/or hemolysis. Genetic loci coding for three types of human PFK subunit - liver (L), muscle (M) and platelet (P) have been mapped by immunoprecipitation of protein synthesized in somatic cell hybrids to human chromosomes 21 (PFKL), 1 (PFKM) and 10 (PFKP). However, studies of the expression of individual PFK genes in human disease has been limited by lack of specific PFK DNA probes. We have used a human astrocytoma cDNA library, in conjunction with a mouse PFK cDNA probe, to isolate four human cDNA clones encoding at least three types of human PFK subunit. Complete DNA sequencing of one cDNA insert reveals 95% amino acid homology with rabbit muscle PFK (234 amino acids compared). Using a panel of mouse-human somatic cell hybrids, we have found that this human cDNA insert is derived from chromosome 12. Mutations in this previously unrecognized human PFK gene may be responsible for the severe mental retardation observed in several recently described patients with PFK deficiency.