Effects of a dietary excess of leucine on the metabolism of tryptophan in the rat: a mechanism for the pellagragenic action of leucine

Bender, David A.

doi:10.1079/bjn19830068

Cited by 58 publications

(52 citation statements)

References 11 publications

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“…Furthermore, it is important to note that when tryptophan is diverted to produce kynurenic acid and quinolic acid, the amino acid is then less available for serotonin synthesis. Only approximately 1% of available tryptophan goes on to metabolize into serotonin, and it has recently been demonstrated that 5‐HT and kynurenine compete for available tryptophan, which leads to serotonin dysfunction during acute stress (Bender, ; Keszthelyi et al, ). However, the complex role of kynurenine is beyond the scope of this review.…”

Section: Serotoninmentioning

confidence: 99%

Neurotransmitters: The Critical Modulators Regulating Gut–Brain Axis

Mittal

Debs

Patel

et al. 2017

Journal Cellular Physiology

421

287

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Neurotransmitters including catecholamines and serotonin play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the “fight or flight” response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has demonstrated that neurotransmitters can play a significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin have recently been a topic of interest because of their roles in the gut physiology and their potential roles in gastrointestinal and central nervous system pathophysiology. These neurotransmitters are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, gastrointestinal innate immune system, and the microbiome. Furthermore, in pathological states such as inflammatory bowel disease (IBD) and Parkinson’s disease, the levels of these neurotransmitters are dysregulated, therefore causing a variety of gastrointestinal symptoms. Research in this field has shown that exogenous manipulation of catecholamine serum concentrations can help in decreasing symptomology and/or disease progression. In this review article, we discuss the current state-of-the-art research and literature regarding the role of neurotransmitters in regulation of normal gastrointestinal physiology, their impact on several disease processes, and novel work focused on the use of exogenous hormones and/or psychotropic medications to improve disease symptomology.

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Section: Serotoninmentioning

confidence: 99%

Neurotransmitters: The Critical Modulators Regulating Gut–Brain Axis

Mittal

Debs

Patel

et al. 2017

Journal Cellular Physiology

421

287

View full text Add to dashboard Cite

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“…Measurement of NI--methyl nicotinamide W-Methyl nicotinamide in the incubation medium was determined by the small-scale modification of the alkali-ketone fluorimetric method of Carpenter & Kodicek (1 950) that has been described previously (Bender, 1980). Measurement of methyl pyridone carboxamide Methyl pyridone carboxamide in the incubation medium was determined colorimetrically after removal of interfering substances with MB-5 1 13 mixed-bed ion-exchange resin, hypobromite-catalysed rearrangement to the amine, diazotization, and coupling with napthylethylene diamine, as described previously by Bender (1983), a modification of the methods described by Holman (1954) and Joubert & de Lange (1962).…”

Section: Measurement Of Total Niacinmentioning

confidence: 99%

Utilization of tryptophan, nicotinamide and nicotinic acid as precursors for nicotinamide nucleotide synthesis in isolated rat liver cells

Bender

Olufunwa

1988

Br J Nutr

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1. Incubation of isolated rat hepatocytes with nicotinamide or nicotinic acid showed that while both vitamers were taken up from the incubation medium, neither was utilized to any significant extent as a precursor of the nicotinamide nucleotide coenzymes, NAD and NADP, and neither was capable of preventing the loss of nucleotides that occurs on incubating the cells.2. Incubation of hepatocytes with tryptophan showed that de novo synthesis from tryptophan permitted replacement of the nucleotides lost during incubation ; at high concentrations of tryptophan there was an increase above the initial intracellular concentration of NAD(P). Incubation of hepatocytes with tryptophan also resulted in the formation and release from the cells of a considerable amount of niacin, as well as the two principal metabolities of NAD(P), "-methyl nicotinamide and methyl pyridone carboxamide.3. It is suggested that, in the liver, preformed niacin is not utilized for nucleotide synthesis, and indeed the function of the liver appears to be synthesis of niacin from tryptophan, and its release for use by extrahepatic tissues that lack the pathway for de novo synthesis of nicotinamide nucleotides from tryptophan.Previous studies from this laboratory have suggested that the de novo synthesis of nicotinamide nucleotides (NAD and NADP) from tryptophan may be a more important source of these coenzymes than is the utilization of dietary nicotinamide or nicotinic acid. The enzyme kinetic variables are such that the three enzymes involved in the incorporation of preformed niacin into nucleotides, nicotinamide phosphoribosyltransferase (EC 2.4.2.12), arylformamidase (nicotinamide deamidase; EC 3.5.1 -19) and nicotinate phosphoribosyltransferase (EC 2.4.2.11) (see Fig. l), all act at or near their maximum rates at the normal intracellular concentrations of nicotinamide and nicotinic acid (Bender et al. 1982). This suggests that there would be little or no utilization of any additional niacin which might be available from the diet or arising from the catabolism of NAD(P).Feeding rats on diets providing high intakes of either nicotinic acid or nicotinamide leads to a relatively small increase in the concentration of NAD(P) in the liver. A tenfold increase in dietary niacin resulted in only a 50 % increase in liver NAD(P). By contrast, a threefold increase in dietary tryptophan resulted in a 2.6-fold increase in liver NAD(P), as well as a very considerable increase in the urinary excretion of "-methyl nicotinamide and methyl pyridone carboxyamide, the two principal metabolites of nicotinamide, resulting from hydrolysis of NAD(P) (McCreanor & Bender, 1986).The present study was undertaken in order to investigate further the relative importance of utilization of preformed niacin and de novo synthesis from tryptophan in the synthesis of nicotinamide nucleotide coenzymes in isolated rat hepatocytes. METHODS Cell preparation and incubationsMale Wistar rats, weighing 200 g, fed from weaning on animal house stock diet (Diet 86;

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“…Magboul & Bender (1983) have confirmed that a relative excess of leucine in the diet inhibits the synthesis of NAD(P) from tryptophan in rats. A number of factors may be involved, including: competition between kynurenine and tryptophan for uptake into tissues; increased activity of picolinate carboxylase (Bender, 1983) and inhibition of kynureninase by leucine and of kynurenine hydroxylase by a-oxoisocaproate, the 0x0 acid of leucine (Magbod& Bender, 1983). This last is unlikely to be physiologically important.…”

mentioning

confidence: 99%