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At least 19 recordsLinked to original sources
PubMed1986

The risks and benefits of a low protein-essential amino acid-keto acid diet.

Twelve patients with progressive renal failure were placed on a very low protein diet supplemented by an essential amino acid-keto acid mixture for six to twelve months. Total daily intake was 0.04 g nitrogen/kg and 50 kcal/kg. Eight subjects had a significant change in the slope of reciprocal plasma creatinine, becoming less steep and in two cases positive. GFR did not improve, but in four patients the decline over twelve months was less than 0.5 mliter/min. There were significant falls in blood and urinary urea, serum phosphate PTH and calcium X phosphate product. Body wt decreased during the first three months. Arm muscle circumference fell by 0.9 cm (P less than 0.005). Serum albumin and transferrin levels did not change significantly. Muscle mass and plasma creatinine fell simultaneously in several patients. Creatinine excretion per kg muscle mass, assessed anthropometrically, declined by 21% in the first three months. This diet may slow the decline in renal function in a proportion of patients. However, muscle mass can be lost. Serum protein levels do not accurately reflect nutritional changes. A fall in plasma creatinine may not be due to improved GFR but instead to altered creatinine metabolism.

Adult↗
PubMed1977

Maple syrup urine disease: branched-chain keto acid decarboxylation in fibroblasts as measured with amino acids and keto acids.

Branched-chain keto acid decarboxylase activity in skin fibroblasts from control subjects and from patients with classical and variant forms of maple syrup urine disease (MSUD) was measured with leucine and alpha-ketoisocaproic acid. When the keto acid was used as substrate in high concentrations (more than 5 mM), the three groups overlapped extensively, even classical cases of MSUD exhibiting decarboxylase activity. With leucine as substrate, decarboxylase activity plateaued at about 1.5 mM, and the three groups could be clearly differentiated. Classical cases of MSUD had minimal or no decarboxylase activity.

Caproates↗
PubMed1991

[The effect of metabolic acidosis on amino acid and keto acid metabolism in chronic renal failure].

The effect of metabolic acidosis (MA) on amino acid and keto acid metabolism was studied in fourteen patients with chronic renal failure (CRF) under the low protein diet (0.6-0.8 g/kgBW). The comparative study of five patients with renal tubular acidosis was carried out. Each patient was investigated before [MA(+)period] and after correction with sodium bicarbonate administration lasting 10 days [MA(-)period]. The correction of MA improved nitrogen balance and elevated plasma branched-chain amino acids (BCAA), keto acids (BCKA), glutamine and alanine concentrations. No effect was however, observed in change of plasma insulin and glucagon. Oral administration of the keto-analogues of BCKA [0.1 g/kgBW of alpha-ketoisovalerates (KIV) and alpha-keto-isocaproic acid (KIC)] is made for the purpose of investigating the change in the metabolic conversion rate to amino acids. As a result, MA (+) suppressed an increase in plasma KIV and KIC concentrations. Moreover, an increase in plasma valine and leucine concentrations were suppressed by MA (+). These results suggested that MA stimulates BCKA oxidation and suppresses the protein sparing effect of leucine and KIC, and accelerates the catabolism in CRF under the low protein diet. The correction of MA is ineffective in severe renal failure (serum creatinine above 10.0 mg/dl), because the other uremic factors appear to be affecting protein and amino acid metabolism. Therefore, it might be concluded that MA should be corrected at an earlier stage of CRF.

Acidosis, Renal Tubular↗
PubMed1977

Effects of branched-chain amino acid antagonism in the rat on tissue amino acid and keto acid concentrations.

Growth rate, plasma amino acid, and alpha-keto acid concentrations and activities of the branched-chain amino acid degradative enzymes of rats were measured. Effects of ingestion of excessive amounts of branched-chain amino acids on these variables were determined. Excessive intake of a single branched-chain amino acid led rapidly to elevated plasma concentration of both the amino acid administered and its corresponding alpha-keto acid and, if the rats had previously been fed a low protein diet, to an increase in liver branched-chain alpha-keto acid dehydrogenase activity. Only leucine caused, in addition, marked growth and food intake depression and decreased plasma isoleucine, valine, alpha-keto-beta-methylvaleric acid and alpha-keto isovaleric acid concentrations. The growth depression was associated food intake depression and could be moderated by addition of isoleucine and valine to the diet. The decreases in plasma isoleucine, valine, alpha-keto-beta-methylvaleric acid and alpha-keto isovaleric acid were not caused by increased degradation of these metabolites to carbon dioxide as branched-chain amino acid oxidation rates in vivo were unchanged by leucine loading and the degradative enzymes were unchanged in adequately fed rats. The decreased concentrations of these amino and keto acids may be the result of decreased protein degradation or increased protein synthesis, possibly mediated by insulin.

Alanine↗
PubMed1977

Influence of essential amino acids and keto acids on protein metabolism and the anaemia of patients on chronic intermittent haemodialysis.

Ten patients were treated with 10 g essential amino acids per day orally; 9 patients received 9.5 g of a mixture of essential amino acids (Lys, Thr, Try, His, Tyr) and ketoanalogues of Ile, Leu, Phe, Val, Met per day and a control group of 11 patients received no supplementation. All patients were on a liberal food intake amounting to 1g protein/kg body weight and 31 kcal/kg body weight daily. Before and three months after the beginning of supplementation the following parameters were measured: serum concentrations of albumin, transferrin, urea, creatinine, blood haemoglobin content and haematocrit, activities of the enzymes delta-aminolevulinic acid dehydrase and porpho-bilinogen desaminase, and globin synthesis in peripheral red blood cells. After treatment with either essential amino acids or keto acids a significant stimulation of globin synthesis occurred. None of the other parameters was altered. It is concluded that in well-nourished patients supplements of essential amino acids or keto acids are ineffective.

Amino Acids, Essential↗
PubMed1988

Amino acids and keto acids in the treatment of chronic renal failure.

Clinical trials using very low protein supply supplemented with amino acid or keto acid preparations have shown the possibility of slowing the rate of decline of renal function in patients with advanced chronic renal failure together with preservation of nutritional status. The possible mechanisms by which this effect is obtained are reviewed. The potential advantages of keto acids upon amino acids, the optimal composition of the preparations used, and the best time to start treatment in chronic uremics are discussed. Projection of recent data indicate that a prolongation of renal autonomy of about 4 years instead of a spontaneous duration of 15 months until dialysis can be expected using keto acid treatment if started when plasma creatinine reaches 500 mumol/l.

Amino Acids↗
PubMed1978

Nitrogen balance in uremic patients on different amino acid and keto acid formulations--a proposed reference pattern.

Nitrogen balance was studied in 12 uremic patients given nitrogen intakes in varying formulations, either solely as amino acids or as keto acid and amino acid mixtures. It was shown that of the three formulas studied, the one that was most effective in promoting positive balance was the one having threonine as reference unit, with a relatively high tyrosine intake and lower methionine content, and histidine in the proportions found in human milk and in the egg pattern. Also, in all instances in which an amino acid formulation caused a deviation in nitrogen balance, the same effect was obtained with formulations containing keto acids. However, the effect with the keto acids was less pronounced.

Adolescent↗
PubMed1984

Differences in properties between aromatic amino acid: aromatic keto acid aminotransferases and aromatic amino acid: alpha-ketoglutarate aminotransferases.

Homogenates of rat liver transaminate phenylpyruvate (PP), as well as alpha-ketoglutarate (alpha-KG), in the presence of L-tyrosine, 3,4-dihydroxyphenylalanine (L-DOPA) or L-tryptophan. Aminotransferase activity with phenylpyruvate and DOPA, but not with tyrosine, was inhibited by excess phenylpyruvate. Tyrosine and DOPA aminotransferase activities with phenylpyruvate were more heat stable than the corresponding activities with alpha-ketoglutarate. Aminotransferase activities with phenylpyruvate were not significantly induced following intraperitoneal injections of cortisol, glucagon or serotonin, compared with a 3 to 7-fold increase in the aminotransferase activities with alpha-ketoglutarate. Tyrosine:phenylpyruvate aminotransferase activity rose 40% at night, compared with a 300% increase in tyrosine:alpha-ketoglutarate aminotransferase activity. The results suggest that aminotransferases catalysing transfers between aromatic keto acids and aromatic amino acids are separate enzymes from those utilizing alpha-ketoglutarate as the acceptor keto acid.

Animals↗
PubMed1990

Versatile stable isotope technique for the measurement of amino acids and keto acids: comparison with radioactive isotope and its use in measuring in vivo disposal rates.

Tracer methods using both carbon-13 and -14 have been utilized for determination of ovine fetal amino acid disposal and the results compared in seven animals. We infused [1-13C]leucine simultaneously with [1-14C]leucine into the fetal circulation of pregnant sheep chronically catheterized during late gestation. Radioactive and stable isotope enrichments of leucine (Leu) and stable isotope enrichments of ketoisocaproic acid (KIC) in the umbilical artery and vein and the maternal artery and uterine vein were measured. Stable isotope enrichments and concentrations of both Leu and KIC were determined from a single 0.2-ml sample by the use of internal standards and electron ionization GC/MS analysis after a simple isolation and derivatization procedure. The KIC/Leu enrichment ratio was measured for the first time in fetal arterial plasma and was 0.66 +/- 0.05 (SE). Fetal leucine disposal rate was 9.0 +/- 0.5 (SE) micron/min/kg. Disposal rates determined by stable isotopes were not different from those determined by radioactive isotopes. The GC/MS stable isotope method provided higher precision in both leucine concentration and enrichment measurements and has been shown to be a general method for the determination of concentration and isotopic enrichment of other amino acids and their corresponding keto acids. Furthermore, this method is ideally suited to clinical studies where large numbers of samples of rather small volume can easily be studied with a short turnaround time.

Amino Acids↗
PubMed1983

Supplements containing amino acids and keto acids in the treatment of chronic uremia.

Three mixtures containing varying proportions of threonine, tyrosine, and the ornithine, lysine, and histidine salts of branched-chain keto acids have been tested as dietary supplements to a 20- to 25-g mixed-quality protein diet in patients with severe chronic uremia. Two of the three supplements improved the abnormalities of plasma amino acid concentrations, and slowed or arrested progression of renal insufficiency. The second supplement, which contained less threonine and lysine, led to subnormal plasma concentrations of these two amino acids and aggravated hypophosphatemia. The third supplement, which also contained a small amount of the hydroxy analogue of methionine, was the most effective in slowing progression. The results emphasize the importance of optimizing the composition of such supplements.

Amino Acids↗
PubMed1990

High branched-chain alpha-keto acid intake, branched-chain alpha-keto acid dehydrogenase activity, and plasma and brain amino acid and plasma keto acid concentrations in rats.

Diets containing high quantities of individual branched-chain alpha-keto acids (BCKAs) or a combination of BCKAs as used for treatment of renal disease were fed to rats. When the diet contained a single BCKA, its concentration was high in plasma and the concentration of its corresponding amino acid was high in plasma and brain. Liver BCKA dehydrogenase (BCKD) was 42% active in control rats. Consumption of diets containing 0.38 mol/kg diet of alpha-ketoisocaproate (KIC), alpha-keto-beta-methylvalerate (KMV), or alpha-ketoisovalerate (KIV) resulted in complete activation of liver BCKD. Consumption of the diet containing the combination of BCKAs increased basal BCKD activity of liver twofold. Muscle BCKD was activated after feeding the KIV diet (2-fold), the KIC diet (3-fold), and the KMV diet (15-fold). Total BCKD activity of liver and muscle was unaffected by dietary treatments. Activation of liver and muscle BCKD by dietary BCKA is consistent with their ability to inhibit BCKD kinase in vitro.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1984

Nitrogen balance studies in patients with uremia during treatment with protein-reduced diet and supplementation with essential amino acids or keto acids.

Nitrogen balance was studied in 4 patients with uremia during treatment with a protein-reduced diet (20 g) supplemented with either essential amino acids and histidine or a mixture of keto analogues of five of the essential amino acids and essential amino acids. 3 patients completed the study. Nitrogen balance was negative on the diet only and was improved with both forms of supplementation. However, supplementation with the keto acids did not offer any advantage over the conventional essential amino acid supplementation. 1 patient developed serious hypercalcemia during treatment with the keto acid supplementation.

Adult↗