Relationship between proline balance in the rat kidney and intrarenal concentration of amino acids

Abstract

Summary In the present study, a proline‐deficient diet was fed to rats in order to reduce the plasma proline concentration to that observed during fasting and then the carotid‐artery‐renal‐vein differences in various amino acids and intrarenal amino acid concentrations were measured in order to investigate the kinetics of amino acid metabolism in the kidney. The plasma proline concentration in the carotid arteries of the proline‐deficient diet group 8 h after the beginning of the last feed was significantly lower than that in the control group, and the concentration of proline was as low as that of the fasted rats in the control group. The results of the carotid artery‐renal vein difference in proline showed that, at 8 and 16 h after the beginning of the last feed, proline was absorbed by the kidney in the control group and was released from the kidney in the proline‐deficient diet group. The results of the carotid artery‐renal difference in arginine 8 h after the beginning of the last feed showed that the amount of arginine released from the kidney was significantly lower in the proline‐deficient diet group than in the control diet group. The results of the carotid artery‐renal vein difference in intrarenal free amino acids 8 h after the beginning of the last feed showed that the concentrations of amino acids that are metabolically related to proline, such as, arginine, ornithine and alanine, were significantly lower in the proline‐deficient diet group than in the control diet group. There was significant positive correlation between the intrarenal proline concentration and the arteriovenous difference in proline 8 h after the beginning of the last feed (r = 0.653, p < 0.05). At 8 h after the beginning of the last feed, the release of proline from the kidney was observed in the proline‐deficient diet group, and there was significant positive correlation between the carotid‐artery‐vein difference in proline and intrarenal arginine concentration (r = 0.887, p < 0.05). The above findings suggest that when the intrarenal proline concentration decreases, proline is released from the kidney, and when the intrarenal proline concentration increases, proline is absorbed by the kidney. In addition, when the amount of proline released from the kidney increases, the intrarenal arginine concentration decreases. In combination, these results indicate that a portion of the proline released from the kidney is synthesized from arginine in the kidney. Zusammenfassung Beziehung zwischen der Prolinbilanz der Rattenniere und der intrarenalen Aminosäurekonzentration. Nach Fütterung von Ratten mit prolinfreiem Futter ergaben sich so niedrige Serumprolinkonzentrationen, wie sie bei fastenden Ratten beobachtet wurden. In der vorliegenden Studie untersuchten wir die Dynamik des Aminosäuremetabolismus in der Niere, indem wir in diesem Zustand die Prolinkon‐zentrationsdifferenz swischen der A. carotis und der V. renalis und die Konzentration der freien Aminosäuren in der Niere bestimmten. Die Messung der Plasmaprolinkonzentration in der A....

Proline catabolism is a key factor facilitating Candida albicans pathogenicity

“…Interestingly, the kidney is a hub for arginine/proline biosynthesis, which likely increases local concentrations of arginine/proline that contribute to rapid filamentation in C . albicans [ 60 – 62 ]. Two-photon microscopy has previously been used to image fungal infections in translucent mouse pinna (ears) [ 90 ], however, to our knowledge, our studies represent the first in which C .…”

“…Previous work showed that compared to other organs, C. albicans filament faster in the kidney suggesting the presence of kidney-specific cues. Interestingly, the kidney is a hub for arginine/proline biosynthesis, which likely increases local concentrations of arginine/proline that contribute to rapid filamentation in C. albicans [60][61][62]. Two-photon microscopy has previously been used to image fungal infections in translucent mouse pinna (ears) [90], however, to our knowledge, our studies represent the first in which C. albicans infections have been imaged under physiological in situ conditions in a complex intravital organ (Fig 6).…”

“…Subsequent work by the same group [59] suggested that compared to other organs, filamentation of C. albicans occurs remarkably fast in the kidney (within 2 h), implicating kidney-specific factors that drive the rapid filamentation. Notably, the kidney is a major hub for arginine and proline biosynthesis and is tightly connected to the metabolic activities in other organs [60][61][62]; arginine biosynthesis in the kidney is derived from citrulline produced from intestinal breakdown of glutamine [61]. To directly test the significance of proline metabolism and to obtain a detailed understanding of nutrient acquisition, we sought to follow the colonization of kidneys in situ in an intact living host.…”

Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

“…While proline and Pycr1 regulation has been linked to Atf4 signalling previously, this was in the context of stem cell differentiation (D'Aniello et al, 2015) and not that of mitochondrial dysfunction. Although it has been suggested that the pancreas is the major site of proline production in vivo (Tran et al, 2021), the kidney has been proposed to operate as a proline-producing organ under conditions of fasting and with low proline diets (Watanabe et al, 1999;Watanabe et al, 1997). Given the high density of mitochondria in proximal kidney tubules, it would be tempting to speculate that high rates of oxidative TCA activity could be important to facilitate proline biosynthesis for use by other organs under conditions of fasting or nutrient scarcity.…”