Abstract
Lack of prolidase I (PD I) leads to prolidase deficiency, a disease characterized by intractable skin lesions, recurrent respiratory infections, and mental retardation. The present study was undertaken to characterize and determine the physiologic roles of different prolidase isoenzymes. Two isoforms of prolidase were isolated from rat kidney. PD I showed higher activity against seryl-proline and alanyl-proline, whereas PD II was active especially against methionyl-proline. PD I was highly concentrated in the small intestine and kidney, whereas PD II was shown not to vary in the organs examined. Expression of PD I and PD II in the small intestine were maximal within 1 wk of birth, and then rapidly declined. The changes of prolidase in the kidney and heart were found to differ slightly. N-benzyloxycarbonyl-l-proline and captopril inhibited PD I dose-dependently, but showed no inhibition of PD II at low concentrations. NiCl2 inhibited PD II much more effectively than PD I. Our findings suggest that PD I functions by way of an intestinal peptide carrier, which may also be regulated by the uptake of various iminodipeptides. Similarly, age-related alterations of prolidase isoenzymes suggest that intestinal PD II also participates in absorption of proline and other amino acids early in life.
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Abbreviations
- Ala-Pro:
-
alanyl-proline
- Cbz-Proline:
-
N-benzyloxycarbonyl-l-proline
- Gly-Pro:
-
glycyl-proline
- Met-Pro:
-
methionyl-proline
- PD I:
-
prolidase I
- PD II:
-
prolidase II
- PEPT 1:
-
intestinal oligopeptide transporter
- Ser-Pro:
-
seryl-proline
References
Hui KS, Lajtha A 1980 Activation and inhibition of cerebral prolidase. J Neurochem 35: 489–494
Jackson SH, Heininger JA 1975 Proline recycling during collagen metabolism as determined by concurrent 18O2-and 3H-labeling. Biochim Biophys Acta 381: 359–367
Myara I, Charpentier C, Lemonnier A 1984 Prolidase and prolidase deficiency. Life Sci 34: 1985–1998
Donald SP, Sun XY, Hu CA, Yu J, Mei JM, Valle D, Phang JM 2001 Proline oxidase, encoded by p53-induced gene-6, catalyzes the generation of proline-dependent reactive oxygen species. Cancer Res 61: 1810–1815
Maxwell SA, Rivera A 2003 Proline oxidase induces apoptosis in tumor cells, and its expression is frequently absent or reduced in renal carcinomas. J Biol Chem 278: 9784–9789
Powell GF, Rasco MA, Maniscalco RM 1974 A prolidase deficiency in man with iminopeptiduria. Metabolism 23: 505–513
Kodama H, Umemura S, Shimomura M, Mizuhara S, Arata J, Yamamoto Y, Yasutake A, Izumiya N 1976 Studies on a patient with iminopeptiduria. I. Identification of urinary iminopeptides. Physiol Chem Phys 8: 463–473
Der Kaloustian VM, Freij BJ, Kurban AK 1982 Prolidase deficiency: an inborn error of metabolism with major dermatological manifestations. Dermatologica 164: 293–304
Jackson SH, Dennis AW, Greenberg M 1975 Iminodipeptiduria: a genetic defect in recycling collagen; a method for determining prolidase in erythrocytes. Can Med Assoc J 113: 759–763
Powell GF, Kurosky A, Maniscalco RM 1977 Prolidase deficiency: report of a second case with quantitation of the excessively excreted amino acids. J Pediatr 91: 242–246
Sheffield LJ, Schlesinger P, Faull K, Halpern BJ, Schier GM, Cotton RG, Hammond J, Danks DM 1977 Iminopeptiduria, skin ulcerations, and edema in a boy with prolidase deficiency. J Pediatr 91: 578–583
Butterworth J, Priestman D 1984 Substrate specificity of manganese-activated prolidase in control and prolidase-deficient cultured skin fibroblasts. J Inherit Metab Dis 7: 32–34
Priestman DA, Butterworth J 1984 Prolidase deficiency: characteristics of human skin fibroblast prolidase using colorimetric and fluorimetric assays. Clin Chim Acta 142: 263–271
Kodama H, Ohhashi T, Ohba C, Ohno T, Arata J, Kubonishi I, Miyoshi I 1989 Characteristics and partial purification of prolidase and prolinase from leukocytes of a normal human and a patient with prolidase deficiency. Clin Chim Acta 180: 65–72
Myara I 1987 Effect of long preincubation on the two forms of human erythrocyte prolidase. Clin Chim Acta 170: 263–270
Myara I, Cosson C, Moatti N, Lemonnier A 1994 Human kidney prolidase-purification, preincubation properties and immunological reactivity. Int J Biochem 26: 207–214
Nakayama K, Awata S, Zhang J, Kaba H, Manabe M, Kodama H 2003 Characteristics of prolidase from the erythrocytes of normal humans and patients with prolidase deficiency and their mother. Clin Chem Lab Med 41: 1323–1328
Ohhashi T, Ohno T, Arata J, Sugahara K, Kodama H 1990 Characterization of prolidase I and II from erythrocytes of a control, a patient with prolidase deficiency and her mother. Clin Chim Acta 187: 1–10
Liu G, Nakayama K, Sagara Y, Awata S, Yamashita K, Manabe M, Kodama H 2005 Characterization of prolidase activity in erythrocytes from a patient with prolidase deficiency: comparison with prolidase I and II purified from normal human erythrocytes. Clin Biochem 38: 625–631
Bradford MM 1976 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254
Chinard FP 1952 Photometric estimation of proline and ornithine. J Biol Chem 199: 91–95
Endo F, Tanoue A, Nakai H, Hata A, Indo Y, Titani K, Matsuda I 1989 Primary structure and gene localization of human prolidase. J Biol Chem 264: 4476–4481
Hu M, Cheng Z, Zheng L 2003 Functional and molecular characterization of rat intestinal prolidase. Pediatr Res 53: 905–914
Shen H, Smith DE, Brosius FC 3rd 2001 Developmental expression of PEPT1 and PEPT2 in rat small intestine, colon, and kidney. Pediatr Res 49: 789–795
Guandalini S, Rubino A 1982 Development of dipeptide transport in the intestinal mucosa of rabbits. Pediatr Res 16: 99–103
Wu G, Morris SM Jr 1998 Arginine metabolism: nitric oxide and beyond. Biochem J 336: 1–17
Wu G 1997 Synthesis of citrulline and arginine from proline in enterocytes of postnatal pigs. Am J Physiol 272: G1382–G1390
Davis TA, Nguyen HV, Garcia-Bravo R, Fiorotto ML, Jackson EM, Lewis DS, Lee DR, Reeds PJ 1994 Amino acid composition of human milk is not unique. J Nutr 124: 1126–1132
Lupi A, Rossi A, Vaghi P, Gallanti A, Cetta G, Forlino A 2005 N-benzyloxycarbonyl-L-proline: an in vitro and in vivo inhibitor of prolidase. Biochim Biophys Acta 1744: 157–163
Ganapathy V, Pashley SJ, Roesel RA, Pashley DH, Leibach FH 1985 Inhibition of rat and human prolidases by captopril. Biochem Pharmacol 34: 1287–1291
Miltyk W, Surazynski A, Kasprzak KS, Fivash MJ Jr, Buzard GS, Phang JM 2005 Inhibition of prolidase activity by nickel causes decreased growth of proline auxotrophic CHO cells. J Cell Biochem 94: 1210–1217
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Liu, G., Nakayama, K., Awata, S. et al. Prolidase Isoenzymes in the Rat: Their Organ Distribution, Developmental Change and Specific Inhibitors. Pediatr Res 62, 54–59 (2007). https://doi.org/10.1203/PDR.0b013e3180676d05
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DOI: https://doi.org/10.1203/PDR.0b013e3180676d05
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