Disturbance of Creatine Metabolism in Rats with Chronic Renal Failure

Inouchi, Masato; Fujino, Tomoya; Sato, Takeo; Yasuda, Takashi; Tomita, Hayato; Kanazawa, Tsukasa; Shiba, Chikako; Ozawa, Shun; Ohwada, Shigeru; Ishida, Masaharu

doi:10.1007/978-1-4613-0821-8_34

Cited by 1 publication

(4 citation statements)

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“…Although GAA synthesis has been demonstrated to be lowered in the uremic kidney, there are few data showing impaired conver sion from Arg to GAA in uremia. Inouchi et al [15] and Owada et al [16] observed impaired conversion from Arg to GAA in CRF rats by using radioactive substances, although these results were demonstrated only semiquantitatively. Therefore, GAA metabolism must be investigated more fully in the uremic state.…”

Section: Introductionmentioning

confidence: 84%

“…Although GAA production in CRF has been studied with some radioactive substances [15,16], the results are not sufficient to explain directly the impairment of GAA meta bolism in CRF because a relationship between GAA pro duction and renal GAT activity was not demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…Owada et al [16] reported that the radioactivity of intrarenal l4C-GAA in the CRF group was significantly lower than in the normal group at 60 and 120 min after the injection of l4C-Arg. Inouchi et al [15] reported that the conversion rate of l4C-Gly to l4C-GAA detected radiochromatographically was 50% lower in CRF rats than that in a normal group 10-60 min after the injection of l4C-Gly. The author measured l4C-GAA from an earlier point and at shorter intervals after injection compared with these two studies and could obtain clearer results showing significantly lower levels of serum AI4C-GAA in the CRF group.…”

Section: Discussionmentioning

confidence: 99%

“…This substance plays an important role in muscle energy metabolism as a precursor of creatine (CR) and is synthesized from arginine (Arg) and glycine (Gly) by glycine amidinotransferase(GAT) mainly in the kidney and thereafter to C'R by GAA methyltransferase (GAA-MT) in the liver [7][8][9], It has been reported that in uremia, GAA production is reduced because of decreased GAT activity in the kidney, resulting in a lower concentration of serum GAA with a significant negative correlation with blood urea nitrogen (BUN) [10][11][12][13]. It has been suggested that GAA deficiency caused by the reduced production of GAA re sults in a CR deficiency in the uremic state [10][11][12][13][14][15]. Tsubakihara et al [12] reported that in chronic renal failure (CRF) rats, CR increased in each organ, while muscle strength and activity recovered when GAA was supplemented.…”

Section: Introductionmentioning

confidence: 99%

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Study on Impaired Metabolism of Guanidinoacetic Acid in Chronic Renal Failure Rabbits with Special Reference to Impaired Conversion of Arginine to Guanidinoacetic Acid

Kuroda

1993

Nephron

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Most chronic renal failure (CRF) patients show low serum concentrations of guanidinoacetic acid (GAA). In this study, the author investigated the impaired metabolism of GAA in CRF focusing on the transformation of arginine (Arg) to GAA by analyzing CRF rabbits using ¹⁴C-Arg. The CRF group which consisted of 6 CRF rabbits, was compared with 6 normal rabbits (normal group). Blood samples were obtained from each abdominal aorta after a bolus injection of 30 μCi of ¹⁴C-Arg into an ear vein of each rabbit. After the last sampling, the left kidney was obtained for measurement of renal glycine amidinotransferase (GAT) activity. In each blood sample, the concentrations of blood urea nitrogen (BUN), serum creatinine (Cr), GAA and Arg were measured. The radioactivity of serum ¹⁴C-GAA was measured with a liquid scintillation system. Δ¹⁴C-GAA was calculated as the difference between the ¹⁴C-GAA count and the Δ¹⁴C -background count. Serum concentrations of GAA and renal GAT activity were significantly lower in the CRF group as compared with the normal group. Significant negative correlations were found between the two groups for the following comparisons: serum concentrations of Cr and GAA, concentrations of BUN and renal GAT activity, and serum concentrations of Cr and renal GAT activity. There was a significant positive correlation in the two groups, between renal GAT activity and serum concentrations of GAA. The fact that the concentrations of neither GAA nor Arg changed significantly after the injection of ¹⁴C-Arg in either group suggested that the dosage of injected Arg is not sufficient to affect the transformation of Arg to GAA. After 5 min and at the following 5-min intervals, Δ¹⁴C-GAA was significantly lower in the CRF group than in the normal group. There was a positive correlation between Δ¹⁴C-GAA after 5 min and renal GAT activity. These results clearly show that renal GAT activity decreases with the progression of renal dysfunction, which directly causes a reduced transformation of Arg to GAA in the kidney, resulting in lower serum concentrations of GAA.

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Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%