Christopher J. Danpure

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We have previously shown that in some patients with primary hyperoxaluria type 1 (PH1), disease is associated with mistargeting of the normally peroxisomal enzyme alanine/glyoxylate aminotransferase (AGT) to mitochondria (Danpure, C.J., P.J. Cooper, P.J. Wise, and P.R. Jennings. J. Cell Biol. 108:1345-1352). We have synthesized, amplified, cloned, and(More)
Activities of alanine:glyoxylate aminotransferase in the livers of two patients with primary hyperoxaluria type I were substantially lower than those found in five control human livers. Detailed subcellular fractionation of one of the hyperoxaluric livers, compared with a control liver, showed that there was a complete absence of peroxisomal(More)
Protein-targeting sequences are specific for each intracellular compartment, so that most proteins are found at only one location within the eukaryotic cell. Increasingly, however, examples are being found of proteins that occur and function in more than one cellular compartment. In some cases, the multicompartmentalized isoforms are encoded by the same(More)
The autosomal recessive disorder primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific pyridoxal-phosphate-dependent enzyme alanine:glyoxylate aminotransferase (AGT). Numerous mutations and polymorphisms in the gene encoding AGT have been identified, but in only a few cases has the causal relationship between genotype and(More)
A deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT) is responsible for the potentially lethal hereditary kidney stone disease primary hyperoxaluria type 1 (PH1). Many of the mutations in the gene encoding AGT are associated with specific enzymatic phenotypes such as accelerated proteolysis (Ser205Pro), intra-peroxisomal(More)
Primary hyperoxaluria type 1 (PH1) is an atypical peroxisomal disorder, as befits a deficiency of alanine:glyoxylate aminotransferase (AGT), which is itself an atypical peroxisomal enzyme. PH1 is characterized by excessive synthesis and excretion of the metabolic end-product oxalate and the progressive accumulation of insoluble calcium oxalate in the kidney(More)
The subcellular distribution of alanine:glyoxylate aminotransferase 1 (AGT1) enzyme activity and immunoreactive protein has been determined in the livers of a variety of mammalian species (marmoset, baboon, cat, rabbit, pig, sheep) using the techniques of post-embedding protein A-gold immunoelectron microscopy and isopycnic density gradient centrifugation.(More)
Not all members of the order Carnivora are carnivorous. Some are omnivorous, and a few, such as the giant panda, Ailuropoda melanoleuca, are almost exclusively herbivorous. Although a number of adaptations to increased plant-eating are recognized within Carnivora, few have been studied at the molecular level. One molecular adaptation to diet that is spread(More)
Although human alanine:glyoxylate aminotransferase (AGT) is imported into peroxisomes by a Pex5p-dependent pathway, the properties of its C-terminal tripeptide (KKL) are unlike those of any other type 1 peroxisomal targeting sequence (PTS1). We have previously suggested that AGT might possess ancillary targeting information that enables its unusual PTS1 to(More)
A deficiency of activity of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT,EC been found in the livers of six patients with primary hyperoxaluria type 1 (PH), including three in whom the tissue was obtained by percutaneous needle biopsy. AGT activity, assayed in unfractionated liver tissue, ranged from 11 to 47% of the mean(More)