Characteristics and partial purification of prolidase and prolinase from leukocytes of a normal human and a patient with prolidase deficiency

Kodama, Hiroyuki; Ohhashi, Toshitaka; Ohba, Chisa; Ohno, Takashi; Arata, Jirô; Kubonishi, Ichiro; Miyoshi, Isao

doi:10.1016/0009-8981(89)90297-0

Cited by 17 publications

(9 citation statements)

References 13 publications

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“…This result coincides with those of our previous studies [15,16]. The changes of K m and V max values of PD I, PD II and the patient's prolidase by the amino acids in the presence of 1 mM MnCl 2 may be due to an allosteric effect.…”

Section: Resultssupporting

confidence: 92%

Characterization of prolidase activity in erythrocytes from a patient with prolidase deficiency: Comparison with prolidase I and II purified from normal human erythrocytes

Liu

Nakayama

Sagara

et al. 2005

Clinical Biochemistry

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Section: Resultssupporting

confidence: 92%

Characterization of prolidase activity in erythrocytes from a patient with prolidase deficiency: Comparison with prolidase I and II purified from normal human erythrocytes

Liu

Nakayama

Sagara

et al. 2005

Clinical Biochemistry

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“…Prolidase I has a relative molecular mass of about 112000 and the highest activity towards GlyPro, whereas prolidase II has a relative molecular mass of about 185000 and is mainly active towards Met-Pro. Characteristics of the isozymes in patients and controls have been discussed in detail (12)(13)(14)(15)(16). The present paper also reports the prolidase activities for X-Hyp in patients, in their mother and in controls, which are closely correlated with the quantities of XHyp excreted in the urine.…”

Section: Introductionmentioning

confidence: 78%

The Use of Liquid Chromatography-Mass Spectrometry for the Identification and Quantification of Urinary Iminodipeptides in Prolidase Deficiency

Sugahara

Ohno²,

Arata³

et al. 1993

Clinical Chemistry and Laboratory Medicine

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It has been reported that the urine of patients with prolidase deficiency contains various iminodipeptides with a carboxyl-terminal proline (hydroxyproline). These iminodipeptides have hitherto been detected indirectly by acid hydrolysis or enzymatic digestion, followed by amino acid analysis. In the present study, it was shown that X-Pro could be distinguished from Pro-X when the iminodipeptides were analysed directly by liquid chromatography coupled with atmospheric pressure ionization mass Spectrometry (LC/API-MS), with scanning of the protonated molecule ions ([M + H]+). The same procedure also successfully quantified urinary iminodipeptides from patients with prolidase deficiency. A quantitative investigation of two siblings with prolidase deficiency revealed that the patient with severe clinical symptoms excreted more iminodipeptides than the other who did not have serious symptoms. LC/API-MS also revealed iminodipeptides (Gly-Hyp and Pro^Hyp) in the urine of the mother of the patients and in normal volunteers. Patients excreted much more Pro-Hyp than normal volunteers, whereas no quantitative differences were found between the mother and controls. In patients, the excretion of large quantities of X-Pro is due to their very low prolidase activity towards this type of substrate. In the erythrocytes of patients, prolidase activity towards X-Hyp was extremely low; even in the mother and normal volunteers, it was remarkably low in comparison with the activity against X-Pro.

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“…912 drug activation. Prolidase is not a well-studied enzyme, and its polymorphism is poorly understood, but it seemed to be present in patients who experienced prolidase deficiency (20). Therefore, the present study was undertaken to determine how prolidase is regulated in the intestine and to provide additional evidence in support of the presence of a second prolidase (or prolidase II) in the rat intestine.…”

Section: Discussionmentioning

confidence: 98%

“…Different optimal maximum pH has been reported for partially purified prolidase I and prolidase II, derived from leukocytes (20). The optimal pH for prolidase I was approximately 7.2 and for prolidase II was approximately 8.0 (20).…”

Section: Ph Effectmentioning

confidence: 89%

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Functional and Molecular Characterization of Rat Intestinal Prolidase

Cheng

Zheng

2003

Pediatr Res

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Genetic deficiency of prolidase can lead to severe problems in child development, including mental retardation. However, the exact pathogenesis of the disease is unclear. To understand the enzyme's physiologic functions, we studied the regulation of rat intestinal prolidase. The results indicated that 1) the activities of intestinal prolidase and its kinetic parameters (K m and V max ) are site-dependent; 2) the jejunal prolidase activity was the most sensitive to the dietary restriction, and the duodenal and jejunal but not colonic kinetic parameters changed with dietary restriction; 3) the pH activity profile of jejunal prolidase at 24 h postfeeding was different from that at 48 h postfeeding, whereas the inhibition profiles of prolidase were qualitatively independent of dietary restriction; and 4) old-aged rats have lower prolidase activities in the small intestine. We also purified rat intestinal prolidase I to homogeneity. The characterization study indicated that the purified rat intestinal prolidase I is fairly similar to prolidase I from other species with a molecular weight of 116,000, which consisted of two monomers, 58,000 D each. The purified prolidase I has a K m value of 178 M and a V max value of 601 mol · min Ϫ1 · mg protein Ϫ1 . Screening of a rat intestinal cDNA library produced a 1.8-kb fragment that encodes the rat intestinal prolidase. This enzyme has 494 deduced amino acid sequence, which is 96% or 86% identical to mouse or human erythrocyte prolidase I. This represents the first report of a successful attempt to purify and clone an intestinal prolidase and of investigation to study prolidase regulation by diet. Prolidase is essential for the digestion and metabolism of protein, because it is the enzyme responsible for the metabolism of the most abundant protein digest glycyl-proline (GlyPro) and other imino-dipeptides (1). It is also important for endogenous protein metabolism and amino acid recycling, because it participates in collagen metabolism (2). It plays an important role in cellular growth because Chinese hamster cells that lack proline biosynthesis capability could grow normally as long as Gly-Pro and prolidase were present (1). Genetic deficiency of prolidase can lead to severe problems in child development, including abnormal joints, skin lesion (3), skin cancer (4), and mental retardation (5-7). In addition, abnormal prolidase activities were reported to be associated with certain side effects of drugs (8), liver cirrhosis (9), and hepatoma (10). Finally, prolidase has been targeted as a prodrug converting enzymes by various research groups, primarily for the purpose of improving systemic or cellular bioavailability of poorly absorbed drugs (11,12).It is unclear how abnormal expression of prolidase contributes to the pathogenesis of various diseases associated with its deficiency. Previous studies have not generated a definitive cause for the pathogenesis of prolidase deficiency. For example, Dolenga and Hechtman (13) showed that fibroblasts obtained from symptomatic patients ...

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Characteristics and partial purification of prolidase and prolinase from leukocytes of a normal human and a patient with prolidase deficiency

Cited by 17 publications

References 13 publications

Characterization of prolidase activity in erythrocytes from a patient with prolidase deficiency: Comparison with prolidase I and II purified from normal human erythrocytes

Characterization of prolidase activity in erythrocytes from a patient with prolidase deficiency: Comparison with prolidase I and II purified from normal human erythrocytes

The Use of Liquid Chromatography-Mass Spectrometry for the Identification and Quantification of Urinary Iminodipeptides in Prolidase Deficiency

Functional and Molecular Characterization of Rat Intestinal Prolidase

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