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Biomedical subjects

M Walser

Publications and source records attributed to M Walser.

At least 91 records · Page 5Linked to original sources
PubMed1982

Growth of rats fed by a continuous intragastric infusion containing amino acids and keto acids.

A nutrient mixture was designed to minimize electrolyte and nitrogen excretion in rats while permitting growth. It contained lysine, threonine, histidine, tryptophan, ornithine, N-free analogues of the other essential amino acids, sucrose, corn oil, minerals, and vitamins. Intragastric infusion of this mixture for 25 days into 150-g rats with no access to food or water produced an average weight gain (after a 4-day lag period) of 3.48 +/- 0.09 g/day with proportionate increase in tail length. Urinary excretion rates of N, urea, Na, K, and P became very low. Fecal N fell to 4 mg/day. Urine pH averaged 6.1. Plasma amino acid concentrations changed markedly. Carcass analysis showed that an average of 63% of the 144 mg/day of administered N was retained for growth. Thus, this nutrient mixture is unusually efficiently utilized and leads to minimal excretion of waste products.

Amino Acids↗
PubMed1981

Organic acidaemia and Hyperammonaemia: review.

Recent clinical and experimental evidence on the effects of organic acids in producing or ameliorating hyperammonaemia is reviewed. The importance of hepatic mitochondrial N-acetylglutamate and its precursors, glutamate and acetyl-CoA, in the control of ureagenesis and thus blood ammonia levels is emphasized by recent work. The hypothesis is proposed that protein loads stimulated urea cycle activity via glutamate-induced changes in N-acetylglutamate concentration, while the effects of organic acids on ureagenesis are related in a predictable way to their effects on hepatic concentrations of acetyl-CoA.

Acetyl Coenzyme A↗
PubMed1981

Gyrate atrophy of the choroid and retina. Biochemical considerations and experience with an arginine-restricted diet.

Ornithine-delta-aminotransferase deficiency is the primary biochemical defect in gyrate atrophy of the choroid and retina and results in the characteristic accumulation of ornithine. An additional consequence of this inborn error is that arginine, the precursor of ornithine, becomes an essential amino acid. Therefore, to reduce the accumulated ornithine, we placed nine gyrate atrophy patients on an arginine-restricted diet. Plasma ornithine decreased by 50 to 85% within one month. Orally administered, alpha-aminoisobutyric acid facilitated the reduction in ornithine by augmenting renal losses. Over the long term, three patients have maintained near normal plasma ornithine concentrations from 4 to 32 months. Two patients have maintained less striking reductions in ornithine, and four have either been poorly controlled or have terminated the diet. Urinary losses of arginine and ornithine in gyrate atrophy patients with high or low plasma ornithine concentrations are less than 50% of the estimated arginine intake. This observation suggests that the bulk of ingested arginine is somehow metabolized despite the severe reduction in ornithine-delta-aminotransferase activity.

Adolescent↗
PubMed1981

Visual results of a long-term trial of a low-arginine diet in gyrate atrophy of choroid and retina.

Visual function has been serially assessed in two gyrate atrophy patients who have had long-term reduction of plasma ornithine concentrations by a low-arginine diet. One patient demonstrated subjective and objective improvement after 15 months of treatment. In addition to improvements in dark adaptation thresholds, enlargement of visual fields, and a more normal electroretinogram, there was marked improvement in cone function as measured by color vision. There has been no change noted in the second patient. These results suggest that reduction of plasma ornithine may be beneficial in gyrate atrophy patients and that the high ornithine concentrations characteristic of this disorder play some role in the pathophysiology.

Adult↗
PubMed1981

Effects of arginine-free meals on ureagenesis in cats.

Cats given a single arginine-free meal have been reported to develop severe hyperammonemia, attributed to impaired function of ornithine aminotransferase (OAT). We found that cats that developed hyperammonemia following an arginine-free meal had low hepatic ornithine levels. However, the average sum of hepatic ornithine plus arginine plus citrulline rose, indicating that some ornithine synthesis via OAT took place, and hyperammonemia failed to occur in cats with higher hepatic ornithine levels. OAT activity and kinetic constants were comparable to values reported in the rat. Furthermore, dietary supplementation with ornithine caused only occasional and transient hyperornithinemia. Thus, OAT can function in the cat. The Ka of N-acetylglutamate (AGA) synthetase for arginine was 5 times higher in cats than in rats, but AGA content and citrullinogenesis by intact mitochondria were the same following arginine-free or arginine-containing meals. Other kinetic parameters of AGA synthetase and carbamoylphosphate synthetase were similar to values in the rat. We conclude that low levels of hepatic ornithine are probably responsible for making some cats susceptible to hyperammonemia following this stimulus.

Acetyltransferases↗
PubMed1981

Nitrogen sparing induced by leucine compared with that induced by its keto analogue, alpha-ketoisocaproate, in fasting obese man.

We measured the effects of seven consecutive daily infusions of alpha-ketoisocaproate (the alpha-keto analogue of leucine) or leucine itself on urinary urea and total nitrogen excretion during fasting. Two study protocols were undertaken. In protocol I, subjects underwent three separate 14-d fasts: one during which 34 mmol/d of leucine were infused on days 1--7; a second during which 34 mmol/d of alpha-ketoisocaproate were infused on days 1--7; and a third control fast during which no infusions were given. Infusions of alpha-ketoisocaproate significantly reduced daily urine urea nitrogen excretion compared with both the control fasts and the fasts in which leucine was infused (P less than 0.001). This nitrogen-sparing effect of alpha-ketoisocaproate persisted during days 8--14 even though no further infusions were given. Daily urinary urea nitrogen excretion during fasts when leucine was administered did not differ from values observed during control fasts. In protocol II, subjects were starved on two occasions for 14 d. During one fast, infusions of 11 mmol/d of alpha-ketoisocaproate were given on days 1--7; during the control fast, no infusions were given. Daily urine urea nitrogen excretion was lower (P less than 0.001) on days 1--7 and also on days 8--14 of the fast during which alpha-ketoisocaproate was given. The nitrogen-sparing effect of alpha-ketoisocaproate could not be related to changes in circulating levels of amino acids, ketone bodies, or insulin in either protocol. We conclude that alpha-ketoisocaproate infusions decrease the nitrogen wasting of starvation, whereas leucine, studied under identical conditions, does not.

Adult↗
PubMed1980

Gyrate atrophy of the choroid and retina: improved visual function following reduction of plasma ornithine by diet.

In a patient with gyrate atrophy of the choroid and retina, an arginine-deficient diet has reduced plasma ornithine concentration fivefold during the past 20 months. Subjective improvement in her visual function was noted approximately 15 months after institution of her diet. This has been documented by improvements in the electroretinogram, dark-adaptation, and color vision. The improvement involves rod and, to a lesser extent, cone function. The results, although preliminary and limited to a single patient, suggest that reduction of plasma ornithine with a low arginine diet is beneficial in this disease.

Adult↗
PubMed1980

Short term regulation of ureagenesis.

In order to examine the mechanism of the acute response of ureagenesis to amino acid loads, rats were injected intraperitoneally with various doses of a mixture of 20 amino acids. Blood ammonia rose only slightly with doses of 0.5 to 2.0 g/kg, but increased sharply at doses of 3 to 5 g/kg. Carbamyl phosphate synthetase I (EC 2.7.2.5) activity, assayed in intact mitochondria isolated from livers removed 15 min after injection of amino acids, with N-acetylglutamate at its endogenous levels, rose up to 5-fold with increasing doses up to 2 g/kg; no further activation occurred with larger doses. This maximal activity was the same as the activity measured in disrupted mitochondria. Hepatic levels of glutamate and N-acetylglutamate increased approximately linearly with dose of amino acids. The time course of these changes following a dose of 1.5 g/kg was studied. Glutamate, N-acetylglutamate, and carbamyl phosphate synthetase I activity all peaked 5 to 15 min after injection. All of these results were virtually unaltered by omission of arginine from the injected mixture, indicating that the increase in N-acetylglutamate was not attributable to activation by arginine of N-acetylglutamate synthetase. These results indicate that moderate loads of amino acids activate unreagenesis via a rapid increase in N-acetylglutamate levels, secondary to increased mitochondrial glutamate, and independently of injected arginine. This autoregulatory mechanism becomes saturated at large doses of amino acids, and hyperammonemia then supervenes.

Acetyltransferases↗
PubMed1980

Gyrate atrophy of the choroid and retina: amino acid metabolism and correction of hyperornithinemia with an arginine-deficient diet.

Four patients with gyrate atrophy of the choroid and retina were studied, all of whom exhibited the hyperornithinemia characteristic of this disorder. Elevated plasma histidine and diminished plasma lysine and branched-chain amino acids were also noted. The renal clearances of these four amino acids were not sufficiently elevated to explain their low plasma levels. In one subject, an arginine-deficient diet led to progressive reduction in plasma ornithine from 13 times normal to the upper limits of normal, along with the disappearance of ornithinuria and lysinuria. Orally administered alpha-aminoisobutyric acid facilitated the fall in plasma ornithine by increasing renal losses of ornithine. It also increased the clearances of most other amino acids. When plasma ornithine approached normal (less than 200 microM), plasma lysine became normal, plasma arginine became subnormal, and renal clearances of basic amino acids decreased. Long-term (1.5 yr) maintenance with a diet containing 10-20 g of protein plus essential amino acids served to keep plasma ornithine at between 55-355 microM; chorioretinal degeneration did not progress and vision apparently improved.

Adult↗