Urea Metabolism in Man*

Abstract

Urea has long been considered to be metabolically inert. However, recent studies with isotopic urea in several species of animals have revealed that urea is hydrolyzed in the alimentary tract even when administered parenterally (1-5). This breakdown is presumably due to the action of bacterial urease, since urea metabolism can be eliminated or reduced to negligible proportions by the administration of antibiotics.In the studies reported herein, labeled urea was administered intravenously to normal subjects and the rate of extrarenal disposal was determined. Both N15-and C14-labeled materials were employed in order to minimize the problem of reincorporation of tracer atoms into urea. In the case of N'5, enriched ammonia produced by urea hydrolysis in the gut becomes reincorporated into newly formed urea. In the case of C14, recent evidence (6) suggests that reincorporation into urea of labeled CO2, formed by bacterial ureolysis in the gut, may also occur; a conclusion supported by the present experiments.Despite these limitations, the results indicate that 15 to 30 per cent of the urea being synthesized in normal subjects is continually being destroyed. This breakdown can be eliminated by oral administration of neomycin. METHODSUrea containing 60.9 atoms per cent N"5 was synthesized by the ammonolysis of diphenyl carbonate (7) and purified by recrystallization.' The resulting product had a melting point of 130°C. (uncorrected). The nitrogen content was 46.7 per cent (calculated 46.7 per cent).

Caecal pH and ammonia in experimental uraemia.

“…Tracer studies indicate that at least 25 % of the urea in the body undergoes hydrolysis within the gut (Walser and Bodenlos, 1959), but a proportion of the ammonia produced is absorbed and re-synthesized to urea in the liver. The practical importance of this metabolic cycle, therefore, lies in the concentration of ammonia within the gut and its effect on the pH of the gastric and intestinal fluids.…”

Carbon Dioxide Formation and Elimination in Man

“…Fasting adults seem to transport some 4-8 g ( 220-440 mmol) ammonia per 24h via the portal vein to the liver (28,29). Our group has documented enteric release of ammonium ions in piglets (33) of the same magnitude.Out of the endogenous urea production 1530% is hydrolyzed in the gut implying that this amount of ammonium ions (or urea) is recirculating as the faecal content is only 50 mg/24h (29).…”

“…Their calculations of the bicarbonate balance have confirmed that oxidation of many amino acids should in fact generate bicarbonate, but in addition Jungas et a1 (14) have found that the large production of acid (protons) in the urea cycle is balanced within the liver by a local amino acid oxidation generating large amounts of bicarbonate. Furthermore, it now seems to be proven that the same ammonium ion is recirculated and reused for the donation of protons to bicarbonate via an enterohepatic recirculation (16,28,29,30,31,32).…”

“…The breakdown of urea normally takes place in the intestine (28,29,56,57,58,59,60) by means of urease-producing bacteria (61,62) which colonize the newborn infant's intestine, which initially after birth is sterile. This colonization is considered to take place during the first days of life, but according to my hypothesis it is delayed, inhibited or in some other way insufficient in those infants who develop respiratory insufficiency leading to sudden infant death.…”

Relationship between birth weight and urea kinetics in children

“…A portion of urea production is not excreted, but is secreted into the colon, hydrolysed by the resident microflora and the resulting nitrogen containing compounds are salvaged and reutilized in the body (Walser and Bodenlos, 1959). Data by Danielsen and Jackson (1992) have indicated that the ability to maintain urea production is the primary driver of the salvage mechanism.…”