Guanidinoacetic Acid (GAA) Deficiency and Supplementation in Rats with Chronic Renal Failure (CRF)

Tsubakihara, Yoshiharu; Iida, Nobutoshi; Yuasa, Shigekazu; Kawashima, Takashi; Nakanishi, Isao; Tomobuchi, M.; Yokogawa, Tomoko; Ando, Akio; Orita, Yoshimasa; Abe, Hirohito; Kikuchi, Takeo; Okamoto, Hiroki

doi:10.1007/978-1-4757-0752-6_37

Cited by 9 publications

(11 citation statements)

References 7 publications

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“…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. 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.…”

Section: Introductionmentioning

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: 99%

Section: Introductionmentioning

confidence: 99%

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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“…In chronic renal failure (CRF), the reduction of GAA synthesis in the kidney re sulted in the decrease of creatine content in major organs, which induced various uremic symptoms [20], Furthermore, in CRF rats, oral GAA administration recovered creatine content in major organs, muscle power and physical strength [20].…”

Section: Introductionmentioning

confidence: 99%

Intranephron Distribution of Glycine-Amidinotransferase Activity in Rats

Takeda

Koide²,

Jung³

et al. 1992

Kidney Blood Press Res

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Guanidinoacetic acid (GAA), a precursor of creatine, is an essential substrate for muscle energy metabolism, and synthesized by glycine-amidinotransferase (transamidinase) mainly in the kidney. Since the intranephron distribution of transamidinase activity has never been quantified yet, the purpose of this study is to provide evidence about the localization of transamidinase activity using microdissected individual nephron segments. Synthesized GAA was separated by HPLC and detected fluorometrically after reacting with 9,10-phenanthrenequinone. Results obtained were as follows. (1) Transamidinase activity was distributed only in the first (S₁) and the second (S₂) portion of the proximal tubule Si being significantly higher than S₂. (2) In S₂, arginine and glycine were better substrates for GAA synthesis than canavanine and glycine. These results clearly indicate that GAA is synthesized in definite portions of the proximal tubule, and would be transported to the liver for further creatine production.

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“…Dietary GAA improved clinical outcomes and prevented muscle mass loss in patients with chronic renal failure [4]. Supplemental GAA also enhanced muscular performance in healthy volunteers [5] and improved health-related quality of life in patients with chronic fatigue syndrome [6].…”

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confidence: 97%

Advanced physiological roles of guanidinoacetic acid

Ostojić

2015

Eur J Nutr

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Dietary guanidinoacetic acid (GAA) seems to improve cellular bioenergetics by stimulating creatine biosynthesis. However, GAA could have other biological functions that might affect its possible use as a food ingredient in human nutrition. In this paper, we identified several alternative physiological roles of supplemental GAA, including the stimulation of hormonal release and neuromodulation, an alteration of metabolic utilization of arginine, and an adjustment of oxidant-antioxidant status. A better knowledge of how GAA affects human physiology may facilitate its use as an experimental nutritional intervention for novel purposes and conditions.

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Guanidinoacetic Acid (GAA) Deficiency and Supplementation in Rats with Chronic Renal Failure (CRF)

Cited by 9 publications

References 7 publications

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

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

Intranephron Distribution of Glycine-Amidinotransferase Activity in Rats

Advanced physiological roles of guanidinoacetic acid

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