Hyperprolinemia Type II

Applegarth, Derek A.; Ingram, P. L.; Hingston, James; Hardwick, David F.

doi:10.1016/s0009-9120(74)90174-x

Cited by 25 publications

(12 citation statements)

References 10 publications

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“…To verify and extend our findings in cultured fibroblasts, we assayed PC dehydrogenase activity in extracts of fresh peripheral leukocytes obtained from individuals with HP2 and members of their families (Fig. 4) mal (4)(5)(6). all five obligate heterozygotes for HP2 and one of two maternal grandparents in the E. D. family had leukocyte PC dehydrogenase activity at least 2 SD below the normal leukocyte mean (Fig.…”

Section: Resultsmentioning

confidence: 68%

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Type II hyperprolinemia. Delta1-pyrroline-5-carboxylic acid dehydrogenase deficiency in cultured skin fibroblasts and circulating lymphocytes.

Valle¹,

Goodman²,

Applegarth³

et al. 1976

J. Clin. Invest.

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A B S T R A C T Type II hyperprolinemia is an inherited abnormality in amino acid metabolism characterized by elevated plasma proline concentrations, iminoglycinuria. and the urinary excretion of A1-pyrroline compounds. To define the enzymologic defect of this biochemical disorder, we developed a specific, sensitive radioisotopic assay for the proline degradative enzyme A'-pyrroline-5-carboxylic acid dehydrogenase. Using this assay, we have shown an absence of A'-pyrroline-5-carboxylic acid delhydrogenase activity in the cultured fibroblasts from three patients with type II hyperprolinemia. \Ve confirmed this result on cultured cells by demonstrating a similar absence of Al-pyrroline-5-carboxylic acid dehydrogenase activity in extracts prepared from the peripheral leukocytes of these patients. Additionally, we found significantly decreased levels of A'-pyrroline-5-carboxylic acid dehlvdrogenase activity in the leukocyte extracts from five obligate heterozygotes for type II hyperprolinemia. We also demonstrated a reduction in leukocyte AL-pyrroline-5-carboxylic acid dehydrogenase activity in three successive generations of a family.A portion of this work was presented at

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Section: Resultsmentioning

confidence: 68%

“…This OAB-reactive material was initially thought to be PC, but recent evidence shows that the majority of the OAB-reactive material is A'-pyrroline-3-hydroxy-5-carboxylic acid (30HPC), the oxidized degradative product of hydroxyproline (5,6). This observation suggests an abnormality of hydroxyproline degradation in HP2.…”

Section: Resultsmentioning

confidence: 99%

Type II hyperprolinemia. Delta1-pyrroline-5-carboxylic acid dehydrogenase deficiency in cultured skin fibroblasts and circulating lymphocytes.

Valle¹,

Goodman²,

Applegarth³

et al. 1976

J. Clin. Invest.

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“…Adams and Goldstone (7) showed that PC and 3-OH-PC dehydrogenase activities share many physical, chemical, and catalytic properties. Goodman et al (10) and Applegarth et al (11) showed that abnormal amounts of both PC and 3-OH-PC are found in the urine of patients with HP2. This result indicates that derangements in the metabolism of both PC and 3-OH-PC are present in patients with deficient PC dehydrogenase.…”

Section: Discussionmentioning

confidence: 99%

“…In light of these findings, it may seem paradoxical that HP2 patients, who have 10-fold elevations in plasma proline, have only a twofold elevation in plasma hydroxyproline (10,11). This difference in precursor accumulation may be explained by several factors.…”

Section: Discussionmentioning

confidence: 99%

“…The recent discovery by Goodman et al (10) and Applegarth et al (11) that both PC and 3-OH-PC are present in the urine of individuals with HP2 may be explained by either hypothesis. Abnormal 3-OH-PC oxidation in HP2 would be a direct result of the documented deficiency of PC dehydrogenase ifthis enzyme is actually a common A'-pyrroline dehydrogenase.…”

Section: Introductionmentioning

confidence: 97%

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Genetic evidence for a common enzyme catalyzing the second step in the degradation of proline and hydroxyproline.

Valle¹,

Goodman²,

Harris³

et al. 1979

J. Clin. Invest.

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A B S T R A C T The initial step in the degradation pathways of proline and hydroxyproline is catalyzed by proline oxidase and hydroxyproline oxidase, yielding A1-pyrroline-5-carboxylate and A1-pyrroline-3-hydroxy-5-carboxylate, respectively. The second step is the oxidation of A1-pyrroline-5-carboxylate to glutamate and Al-pyrroline-3-hydroxy-5-carboxylate to y-hydroxyglutamate. To determine if this second step in the degradation of proline and hydroxyproline is catalyzed by a common or by separate enzyme(s), we developed a radioisotopic assay for Al-pyrroline-3-hydroxy-5-carboxylate dehydrogenase activity. We then compared Al-pyrroline-3-hydroxy-5-carboxylate dehydrogenase activity with that of Al-pyrroline-5-carboxylate dehydrogenase in fibroblasts and leukocytes from type II hyperprolinemia patients, heterozygotes, and controls. We found that cells from type II hyperprolinemia patients were deficient in both dehydrogenase activities. Furthermore, these activities were highly correlated over the range found in the normals, heterozygotes, and patients.We conclude from these data that a common Alpyrroline-5-carboxylate dehydrogenase catalyzes the oxidation of both Al-pyrroline-5-carboxylate and Alpyrroline-3-hydroxy-5-carboxylate, and that this activity is deficient in type II hyperprolinemia.

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Disorders of Metabolism of Amino Acids and Related Compounds

Arnold

Vockley

2015

Genetic Disorders and the Fetus

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Hyperprolinemia Type II

Cited by 25 publications

References 10 publications

Type II hyperprolinemia. Delta1-pyrroline-5-carboxylic acid dehydrogenase deficiency in cultured skin fibroblasts and circulating lymphocytes.

Type II hyperprolinemia. Delta1-pyrroline-5-carboxylic acid dehydrogenase deficiency in cultured skin fibroblasts and circulating lymphocytes.

Genetic evidence for a common enzyme catalyzing the second step in the degradation of proline and hydroxyproline.

Disorders of Metabolism of Amino Acids and Related Compounds

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