Metabolic transit

Metabolic Transitions and the Role of the Pyruvate Dehydrogenase Complex During Development of Ascaris suum... 

The parasitic nematode, Ascaris suum, undergoes a number of well-characterized metabolic transitions during its development (Table 14.1), but little is known about the regulation of these events (Barrett, 1976 Komuniecki and Komuniecki, 1995). Adults reside in the porcine small intestine and fertilization takes place under low oxygen tensions. The unembryonated egg that leaves the host is metabolically quiescent, has no detectable cytochrome oxidase activity or ubiquinone and appears to be transcriptionally inactive (Cleavinger et al., 1989 Takamiya et al., 1993). Embryonation requires oxygen and after about 48-72 h is accompanied by... 

Table 14.1. Metabolic transitions during the development of Ascaris suum.

In summary, it is clear that A. suum undergoes a number of metabolic transitions during development and, in the case of the pyruvate dehydrogenase complex at least, is constantly fine-tuning the subunit-specific expression and function of the PDC during the course of development. 

Fioravanti, C.F., Walker, D.J. and Sandhu, P.S. (1 998) Metabolic transition in the development of Hymenolepis diminuta (Cestoda). Parasitological Research 84, 777-782. 

Hand, S.C., and J.F. Carpenter (1986). pH-induced metabolic transitions in Artemia embryos mediated by a novel hysteretic trehalase. Science 232 1535-1537. 

Metabolic Transit. Free Amadori Compounds. It is well known that the synthetic Amadori compounds of the free amino acids are absorbed by the intestine and excreted unchanged in the urine (9,28,30). The transport is not active as observed with deoxyfructosyltryptophan (30) and c-deoxyfructosyllysine (40), and the level of absorption depends on the nature of the amino acid and on the conditions of ingestion. Nutritional assays and metabolic transit studies performed with radioactive Amadori compounds of tryptophan (12,30), leucine (12), and lysine (9,28,41) given orally or intravenously on normal or anti-biotics-treated animals have shown that the intestinal microflora can regenerate part of the amino acid. This can be absorbed subsequently at a very low level by the caecum or the large intestine and incorporated into the tissue proteins or utilized by the intestinal microflora. Barbiroli (13) showed also that some intestinal enzymes were able to liberate some amino acids from their Amadori compounds but to a very small... 

It was confirmed later that free cysteic acid and free methionine sulfone were not biologically available (63, 64,138) and that free methionine sulfoxide was partly available. Miller and Samuel (64) observed that the food efficiency of a mixture of free amino acids was lower when the methionine source was replaced by methionine sulfoxide. The food efficiency was restored when 50% of the methionine sulfoxide was replaced by free methionine. Gjoen and Njaa (66) confirmed that free methionine sulfoxide was nearly as available as methionine when the amino acid mixture contained cystine. This suggests that methionine sulfoxide is reduced before it is used for protein synthesis. In order to elucidate this point, we have compared the metabolic transit of free methionine sulfoxide with that of free methionine. 

Metabolic Transit of U-14C-L-Methionine Sulfoxide. U-14C-L-methionine sulfoxide was prepared according to the method of Lepp and Dunn (67) and its metabolic transit on rats was compared with that of free U-14C-L-methionine of the same specific activity (28). 

Metabolic Transit of Free Radioactive e-(y-Glutamyl) lysine. The first metabolic study of this isopeptide was made by Waibel and Carpenter (81) who showed that this molecule was present in the blood plasma of chicks and rats receiving it in their diet. Using c-(y-glutamyl)-[4,5-3H] -lysine, Raczynski et al. (82) confirmed that the isopeptide passed unchanged across the intestinal wall into the serosal fluid in everted sacs and found that the kidneys were very active in hydrolyzing this isopeptide. These authors also found small hydrolytic activities in the intestinal mucosa and the liver. 

We have compared the metabolic transit in rats of e-(y-glutamyl)-U-14C-lysine with that of U-14C-lysine, after ingestion by stomach tubing and intravenous injection (83). 

Table VI. Metabolic Transit of Free 14C-Lysine and Free (y-Glutamyl)-14C-Lysine in Rats°...

In order to elucidate the mechanism of the induction of cytomegaly, we investigated the metabolic transit of lysinoalanine. 

Metabolic Transit of Lysinoalanine. Urinary and Fecal Excretion of Protein-Bound Lysinoalanine (113). Three different alkali-treated proteins (lactalbumin, fish protein isolate, and soya protein isolate) containing, respectively, 1.79, 0.38, and 0.14 g of lysinoalanine/16 g nitrogen were given to rats and the urines and feces were collected. Lysinoalanine was measured before and after acid hydrolysis. The fecal excretion varied from 33 to 51% of the total ingested lysinoalanine and the urinary excretion varied from 10 to 25%. The higher level of lysinoalanine found after acid hydrolysis indicates that a certain quantity is excreted in the urines as combined lysinoalanine (see Table VII). The total recovery was inferior to the ingested quantity (50 to 71%) indicating that the molecule is transformed or retained in the body of the rat. 

Metabolic Transit of 14C-Lysinoalanine in Rats. The radioactive 14C-lysinoalanine was synthesized from uniformly labelled 14C-lysine. The compound a -N-formyl-14C-lysine, prepared according to... 

Table VIII. Metabolic Transit of 14C-Lysinoalanine and Retention in the Liver and the Kidneys0...

Metabolic Transit of 14C-Lysinoalanine in Other Species. In mice and in hamsters, the metabolic transit of lysinoalanine is not very different from that of rats except in the composition of some urinary catabolites (113) and the level of the radioactivity remaining in the kidneys (see Table VIII). In quails the feces contained small amounts of lysinoalanine (6-15%) and only two important catabolites. The urines of mice and hamsters contained two catabolites less than those of rats (see Figure 5), and although mice and hamsters do not develop nephrocytomegaly, they presented the same kind of retention of radioactivity in the kidney cells as rats. This retention in the medular part of the kidneys is well observed on the whole-body autoradiographies of Figure 2 however, in mice and hamsters, this retention is quantitatively less important than in rats (see Table VIII). 

Metabolic Transit of Lysine Bound to Caffeic Acid. In order to follow the metabolism of lysine bound to caffeic acid, goat casein, biologically labelled with tritiated lysine, was treated with caffeic acid at pH 7 with tyrosinase and at pH 10 without tyrosinase and was given to rats. The urinary and fecal excretions and the incorporation of lysine in the tissues were measured (120) (see Figure 6). 

The chemical modifications of the tryptophan residues lead to a decrease in the nutritive value of proteins as observed in autoclaved soja meals (124), heated meats (125), heated casein (126), and heated skim milk (122) this last reference is probably the most reliable work published in this field. The nutritional effects and the metabolic transit of heat-treated and oxidized tripeptide (gly-try—gly) have been investigated (123,132,137) recently only the metabolic transit study is related here. 

Metabolic Transit of Peptide Bound Heat-Treated and Oxidized T ryptophan. The radioactive glycyl-L- (3H) -tryptophylglycine was synthesized by the method proposed by Zimmerman et al. (134) (N-hydroxysuccinimide -j- dicyclohexylcarbodiimide) and treated under the following conditions (a) oxidation by 0.2M hydrogen peroxide at pH 7 for 30 min at 50°C and (b) heat treatment (130°C for 3 h at pH 7) (137). The untreated, oxidized and heat-treated radioactive peptides were given to rats accustomed to eating two meals a day in metabolic cages to collect the urines and feces. 

The metabolic transit studies of the molecules formed provide information complementary to those obtained by the conventional nutritional approaches. This information can be used to control the analytical methods, to explain the nutritional responses, and also to foresee the possible physiological effects. The extrapolation to humans of the results... 

Finot, P.-A., Bujard, E., and Amaud, M. (1977). Metabolic transit of lysinoalanine (IAL) bound to protein and of free radioactive [14C]-lysinoalanine. In "Protein Crosslinking — Nutritional and Medical Consequences," M. Friedman, Ed., Plenum Press, N.Y., pp. 51-71. 

Free radicals are generated from within hepatocytes in several ways, such as ionizing radiation, oxidative metabolism by cytochrome P450, reduction and oxidation (redox) reactions that occur during normal metabolism, transition... 

Reduction metabolic transition time. This relates to the temporality of the lag phase during the transition of a metabolic process from one steady-state to another (see Figure 3). It is a function of metabolite diffusion, enzyme density, and kinetic parameters. Close spatial proximity of sequentially-acting enzymes in organized microcompartments can sharply reduce the temporality associated with reaction-diffusion events for sequences of enzyme reactions in dilute solution. Accordingly, the flux condition in metabolic pathways can rapidly switch in response to external stimuli. 

Figure 3. Graphical definition of the metabolic transition time, x. The concentration of some metabolic product, P, is plotted as a function of time after the pathway is switched on (e.g., by addition of the initial substrate), with the system being devoid of metabolic intermediates initially. The extrapolation to the time axis, of the linear portion of the product accumulation curve is denoted as the transition time (see Welch and Easterby, 1994).

The metabolic transitions that occur as a person eats a meal and progresses through the various stages of fasting have been described in detail in the previous chapters. This chapter summarizes the concepts presented in these previous chapters. Because a thorough understanding of these concepts is so critical to medicine, a summary is not only warranted but essential. 

The chemical and enzymatic browning reactions of plant polyphenols and their effects on amino acids and proteins are reviewed. A model system of casein and oxidizing caffeic acid has been studied in more detail. The effects of pH, time, caffeic acid level and the presence or not of tyrosinase on the decrease of FDNB-reactive lysine are described. The chemical loss of lysine, methionine and tryptophan and the change in the bioavailability of these amino acids to rats has been evaluated in two systems pH 7.0 with tyrosinase and pH 10.0 without tyrosinase. At pH 10.0, reactive lysine was more reduced. At pH 7.0 plus tyrosinase methionine was more extensively oxidized to its sulphoxide. Tryptophan was not chemically reduced under either condition. At pH 10.0 there was a decrease in the protein digestibility which was responsible for a corresponding reduction in tryptophan availability and partly responsible for lower methionine availability. Metabolic transit of casein labelled with tritiated lysine treated under the same conditions indicated that the lower lysine availability in rats was due to a lower digestibility of the lysine-caffeoquinone complexes. 

Goat s milk casein containing tritiated lysine was used to study the metabolic transit of the lysine-caffeoquinone complexes in rats. As before, an aqueous system containing 5 % casein and 0.2 % caffeic acid (4 % by weight of the casein) was stirred and oxygenated for 3 hours at room temperature either at pH 10.0 or at pH 7.0 with tyrosinase. After precipitation and drying, the test materials were fed to rats. The results (Table 3) show that rats fed materials prepared at pH 10.0 or at pH 7.0 with tyrosinase excreted far more radioactivity in their feces than... 

The first part of our study unambiguously demonstrates that the role of carbohydrates is dominant in the formation of CML in drink mixes and that the more protein there is in a food product the less will be the proportion of lysine converted to CML. However this work needs fiirther studies on other types of foods to confirm the origin of CML formed during heat treatment of food. Among the data currently available in the literature the results of our two intervention studies permit to confirm that CML excretion is influenced by dietary CML levels. However the absorption mechanism and the metabolic transit of CML will necessitate further investigation for a full understanding of its utilization in vivo. 

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