Hydroxyproline ingestion and urinary oxalate and glycolate excretion

Abstract

Endogenous synthesis of oxalate is an important contributor to calcium oxalate stone formation and renal impairment associated with primary hyperoxaluria. Although the principal precursor of oxalate is believed to be glyoxylate, pathways in humans resulting in glyoxylate synthesis are not well defined. Hydroxyproline, a component amino acid of collagen, is a potential glyoxylate precursor. We have investigated the contribution of dietary hydroxyproline derived from gelatin to urinary oxalate and glycolate excretion. Responses to the ingestion of 30 g of gelatin or whey protein were compared on controlled oxalate diets. The time course of metabolism of a 10 g gelatin load was determined as well as the response to varying gelatin loads. Urinary glycolate excretion was 5.3-fold higher on the gelatin diet compared to the whey diet and urinary oxalate excretion was 43% higher. Significant changes in plasma hydroxyproline and urinary oxalate and glycolate were observed with 5 and 10 g gelatin loads, but not 1 and 2 g loads. Extrapolation of these results to daily anticipated collagen turnover and hydroxyproline intake suggests that hydroxyproline metabolism contributes 20-50% of glycolate excreted in urine and 5-20% of urinary oxalate derived from endogenous synthesis. Our results also revealed that the kidney absorbs significant quantities of hydroxyproline and glycolate, and their metabolism to oxalate in this tissue warrants further consideration.

Figure 1. Change in plasma hydroxyproline (inset), glycolate (■), and oxalate (–▲–) after ingestion of 10 g gelatin

Each time point represents the mean±s.e.m. *P<0.05 for the comparison of plasma glycolate or hydroxyproline at each post load collection time with the corresponding fasting value.

Figure 2. Urinary glycolate (■) and urinary oxalate (–▲–) following ingestion of 10 g gelatin

Each collection represents the mean±s.e.m. *P<0.05 for the comparison of urinary glycolate or oxalate at each post load collection period with the corresponding fasting value.

Figure 3. The ratio of glycolate clearance to creatinine clearance following 10 g load of gelatin

Each collection represents the mean±s.e.m.

Figure 4. Increases in urinary oxalate (■) and glycolate (□) excretion over fasting levels in a 6-h period following ingestion of various loads of gelatin

Increases in urinary oxalate and glycolate excretion were calculated by subtracting three times the fasting 2 h levels from the total amount measured in each collection. Plasma hydroxyproline (inset) was measured 3 h after ingestion of each load. The asterisk denotes significantly higher (P<0.05) values compared to the 0 g gelatin load. Each parameter represents the mean±s.e.m.

Figure 5. Hydroxyproline transport and metabolism in hepatocytes

Hyp, trans-4-hydroxy-L-proline; GR, glyoxylate reductase; DAO, D-amino oxidase; AGT, alanine:glyoxylate aminotransferase; GO, glycolate oxidase; LDH, lactate dehydrogenase.

Figure 6

| Calibration curve for glycolate determination by ion chromatography coupled with electrospray mass spectrometry.