Excretion of Hydroxyproline in Patients With Rheumatic and Non-Rheumatic Diseases 1

Abstract

The amino acid hydroxyproline constitutes approximately 13 per cent of collagen (1, 2), and 1 to 2 per cent of elastin (2). It is present in no other protein of the body. For this reason, the determination of hydroxyproline has been utilized for the estimation of collagen in various animal tissues (3), and in the fibrinoid material of the subcutaneous nodule of rheumatoid arthritis (4).It is, at the present time, not clear whether in the diseases of the connective tissue, or "collagen diseases," significant alteration and degradation of the protein collagen occurs. The light microscope studies of Klinge (5) and of Bahrmann (6), who observed swelling of collagen in tissue sections of lesions from patients with rheumatic and other diseases, suggested that these changes do occur. Others (7-9) have shown in addition that swelling and focal degeneration of collagen fibers is a common and striking effect of anaphylactoid hypersensitivity reactions.Using the electron microscope, however, Gross (10) and Gale (11) did not find abnormal fibers in material from lesions of rheumatoid arthritis, rheumatic fever, disseminated lupus erythematosus, and scleroderma. Though Wolpers (12) did observe fibrils lacking cross striations in necrotic areas of old rheumatoid nodules, the fibers were normal in non-necrotic areas and in samples of collagen obtained from Arthus lesions. When cross sections of rheumatoid nodules were submitted to careful X-ray diffraction study by Kellgren, Ball, Astbury, Reed, and Beighton (13) In contrast to the preceding workers, Rich, Voisin, and Bang (14) did observe altered fibrils in a small percentage of samples of tissue from Arthus lesions examined with the electron microscope. The fibrinoid material of the subcutaneous nodule of rheumatoid arthritis has recently been extracted (4) and found to contain negligible amounts of hydroxyproline, indicating that, in all probability, it does not contain degraded collagen and arises from other components of the connective tissue.Because hydroxyproline is present almost entirely in collagen, it was felt that if there were a significant deviation from normal in the metabolism of collagen or an increase in degradation of this protein in patients with collagen diseases, these changes might be reflected by increased levels of excretion of this amino acid in urine. METHODSSixty-four patients were studied, of whom 48 were adults ranging in age from 17 to 74, and 16 were children ranging in age from 5 to 14. Twenty-four of the adults were men and 22 women; all but one of the children were boys. Among the adults, 8 were normal individuals and 16 had rheumatoid arthritis. Eight had one of the collagen diseases, i.e., 2 had disseminated scleroderma; 1, isolated scleroderma; 2, disseminated lupus erythematosus; 1, dermatomyositis; and 2, acute rheumatic fever. Sixteen had one of a group of miscellaneous diseases; these included 4 patients with resolving pneumonia, and one patient each with the following conditions: multiple sclerosis, coronary heart disease, acromegaly...

Biochemical Monitoring of Cancer: A Review

“…Studies of its metabolism have shown that the urinary excretion of OHP is related to bone matrix turnover (Prockop and Kivirikko, 1967). It is, thus, not surprising to find that OHP excretion is elevated in bone diseases where there is increased turnover such as some endocrine diseases and rheumatoid disease and in osseous metastatic cancer (Ziff et al, 1956;Benoit et al, 1963;Kivirrikko et al, 1964;Guzzo et a/., 1969). Guzzo et al, (1969) observed that the output of urinary hydroxyproline was increased not only with osseous but also with soft tissue metastases.…”

Urine hydroxyproline correlates with progression of spasticity in cerebral palsy

“…The other 30% is excreted via the urine. It has been suggested that the ratio of hydroxyproline excreted from the lung to that excreted from the urine is fairly constant; therefore, changes in collagen breakdown can be quantified by measuring the changes in the urine concentration of the prolyl-hydroxyproline peptide, which may reflect ineffective peptidase activity (10,11,12). However, no studies have investigated the correlations between the severity of clinical spasticity, Muscle Hydroxyproline (MH), and Urine Hydroxyproline (UH).…”

Effects of lead on collagen synthesis and renal function in the rat

“…The degradation of collagen results in excretion of hydroxyproline in the urine (Ziff et al 1956). From injection of ^^C-proline into young rats, at least three distinct hydroxyproline pools were found, with half-lives of 1, 5, and 50 to 200 days respectively (Lindstedt and Prockop 1961).…”

“…In urine 97% of the hydroxyproline exists as peptides (pro-OHpro and gly-pro-OHpro) (Schrohenloher et al 1958), and only 3% as the free imino acid (Ziff et al 1956). Actually only around 25% of the peptides derived from collagen degradation end up in the urine.…”

“…The free imino acid is rapidly oxidized in liver and kidney by a specific oxidase, resulting in the formation of A' -pyrroline-3-hydroxy-5-carboxylic acid, which is further broken down to urea and .CO2 via y-hydroxy-L-glutamate (Adams 1973). The processes of tissue degradation and of hydroxyproline renal tubular reabsorption are so efficient that only 3% of total urinary hydroxyproline is found as the free imino acid (Ziff et al 1956). …”