Pathways for metabolism

Primary amines are often rapidly inactivited in vitro by one of several pathways for metabolic degration. One of the more... 

A contrasting pathway was found for the metabolism of 2-fluoro-4-nitrobenzoate by Nocardia erythropolis that does not involve loss of fluorine concomitant with decarboxylation (Cain et al. 1968). The pathway (Figure 9.30) therefore differs from what has subsequently emerged as the principal pathway for metabolism of nonhydroxylated 2-halogenated benzoates. 

Marusak RA, Mears CF. 1995. Exploration of selected pathways for metabolic oxidative ring opening of benzene based on estimates of molecular energetics In Valentine JS, Foote CS, Greenberg A, Liebman JE, editors. Active Oxygen in Biochemistry. New York Chapman and Hall. p. 336. 

Drug Therapeutic category enzyme in the major pathway for metabolism of the drug Frequency of poor metabolizer genotypes, % ... 

Figure 2-4 illustrates the minor pathway for metabolism of cyanide in mammalian systems in which cyanide chemically combines with the amino acid cystine. This chemical reaction yields cysteine and B-thiocyanoalanine that is further converted to form 2-aminothiazoline-4-carboxylic acid and its tautomer, 2-iminothiazolidiene-4-carboxylic acid. 

The metabolites of ondansetron have been examined in urine and bile from rat and dog. The major pathways for metabolism of ondansetron are A-demethylation and hydroxylation Scheme 7.7). However, whereas A-de-methylation predominates in dog, this is only a minor metabolic route in rat. Hydroxylation may occur at the 6, 7 or 8 position in the carbazolone ring. Hydroxy metabolites of ondansetron are excreted predominantly as glucuronide or sulphate conjugates. Studies with immobilised glucuronyl-transferase (Heath, S.E., personal communication) have demonstrated that O- and A-glucuronidation of ondansetron metabolites may occur. 

In the preceding chapter, I emphasized the importance of carbohydrates as sources of metabolic energy. I also introduced the idea of metabolic pathways. Now it is time to pull those two themes together and understand how the pathways for metabolism of carbohydrates yield useful metabolic energy and how these processes are controlled. On the way, we will learn how a number of important drugs for human medicine work their therapeutic magic. 

Immune cells play major roles in defence against infection and also in recovery from trauma but, even when these cells are resting (i.e. when there is no or little immune activity), they use glutamine at a high rate to generate ATP (Chapters 9 and 17). The pathway for metabolism of glutamine in these cells is shown in Figure 8.28. 

Between them, the bone marrow and the small intestine possess the highest number of proliferating cells in the body. The bone marrow contains stem cells which proliferate and differentiate to produce red and white blood cells (Chapter 17). This requires not only this amino acids to support protein synthesis but also glutamine, both as a fuel and as a precursor for nucleotides, as in the other proliferating cells. The pathway for metabolism of glutamine in cells isolated from the bone marrow is similar to that in lymphocytes (Figure 8.28). 

Biochemical transformations of the —C=N—OH function of synthetic drugs to an NO and to nitroso intermediates " were recently demonstrated as a new pathway for metabolic activation of oxime-containing molecules. These reactions were recently explored in detail, and may underlie possible biochemical transformations of the —C=N— OH moiety in mammalian tissues, which are likely to be catalyzed by cytochrome P450 and by flavin-containing monooxygenase " . 

C. The branched-chain amino acids Leu, He, and Val share a common pathway for metabolism, which occurs in the peripheral tissues, such as muscle, rather than in the liver (Figure 9-4). 

Figure 9-8. Pathway for metabolism of heme and excretion as bilirubin. Heme degradation begins with heme oxygenase, which catalyzes a complex set of reactions that simultaneously open the protoporphyrin ring structure and release iron in the ferric (Fe ) state. This is the only physiologic reaction that makes endogenous CO in the body a portion of the small amounts made is expired via the lungs. The structure of the main form of bilirubin is shown. Symbols for the side groups indicate M, methyl V, vinyl P, propyl. Formation of the diglucuronide is catalyzed by bilirubin uridine diphosphate (UDP) glucuronyltransferase. RE, reticuloendothelial.

Major metabolic pathways in the brain during starvation. The numbers in the circles, which appear both on the figure and in the corresponding citation in the text, indicate important pathways for metabolism of fat or carbohydrates. 

Figure 13.8 Pathway for metabolism of citrate by Leuconostoc spp. and S. lactis subsp. diacetylactis. (1) Citrate permease, (2) citrate lyase, (3) oxaloacetic acid decarboxylase, (4) pyruvate decarboxylase, (5) a-acetolactate synthetase, (6) a-acetolactate carboxylase, (7) diacetyl synthetase, (8) diacetyl reductase, and (9) acetoin reductase.

Shimabukuro et al. (1966) identified 2-chloro-4-amino-6-isopropylamino-i-triazine (G-30033) as a major metabolite in shoots of mature pea plants. These results indicated that a second mechanism for tolerance to atrazine existed in some moderately susceptible plants. Later, Shimabukuro (1967a) was able to demonstrate that atrazine could be metabolized independently in both roots and shoots of young pea plants to 2-chloro-4-amino-6-isopropylamino-.t-triazine. This metabolite was much less phytotoxic than the parent compound. The metabolism of atrazine in resistant com and sorghum, in intermediately susceptible pea, and in highly susceptible wheat was reported by Shimabukuro (1967b). This study revealed two possible pathways for metabolism of atrazine in higher plants. All species studied were able to metabolize atrazine by TV-deal kyI ation of either of the two alkyl groups present. Com and wheat that contain the cyclic hydroxyamate (2,4-dihydroxy-7-methoxy-l,4-benzoxazine-3-one) also metabolized atrazine by conversion to hydroxy-atrazine (G-34048). Subsequent metabolism was postulated to be by conversion to more polar compounds. 

The Medinsky model (Medinsky et al. 1989a, 1989b, 1989c) is one of the original benzene PBPK models developed to describe and ultimately predict the fate of benzene in mice and rats and to determine if the observed differences in toxic effects could be explained by differences in pathways for metabolism of benzene or by differences in uptake of benzene. 

Medinsky MA, Sabourin PJ, Henderson RF, et al. 1989b. Differences in the pathways for metabolism of benzene in rats and mice simulated by a physiological model. Environ Health Persp 82 43-49. 

Figure 9.3. The two main pathways for metabolism of PTX-2 in shellfish. The oxidative pathway has so far been confirmed only in P. yessoensis. The hydrolytic pathway appears to occur in all other shellfish species studied, including mussels, clams, and other species of scallop.

In all studies thus far made on starch synthetase, the incorporation of D-glucose from a D-glucosyl ester of a nucleotide into an acceptor molecule has been made by using a radioactively labeled D-glucosyl group in the nucleotide ester, and so the results are unambiguous. However, the extent of the incorporation of D-glucose into the acceptor was very low in the early experiments, and the view has been expressed that starch synthetase is not the major pathway for metabolism of starch. This conclusion seems very reasonable starch biosynthesis is probably a multi-pathway process. Of interest in this connection is a comparison that has been made of starch synthetase activity in non-waxy and waxy maize and rice. ... 

Phase II is called the exponential growth phase owing to the fact that tlti cell s growth rate is proportional to the cell concentration. In this phase thq i cells are dividing at the maximum rate because all of die enzyme s pathways for metabolizing the media are in place (as a result of the lag phase) and it)e i cells are able to use the nutrients most efficiently,... 

Fig. 1. Kynurenine pathway for metabolic conversion of tryptophan to niacin.

Because of the wide chemical diversity of estrogenic pharmaceutics, it is difficult to categorize the pathways for metabolic conversion and excretion. However, the majority of these reactions occur in the liver where they are inactivated by various hydro-xylation and oxidation reactions, although the major pathways involve conjugation and excretion in the urine and feces as sulfates and glucuronates. 

Neuronal pathways are quantitatively far more important than extraneuronal pathways for metabolism of the catecholamines synthesized at neuronal locations, such as the norepinephrine produced in sympathetic nerves. The... 

Greenberg, A. Exploration of selected pathways for metabolic oxidative ring opening of benzene... 

Figure 4. Proposed pathway for metabolism of -dimethylaminobenzo-nitrile to a methyIsulfonyl containing acetanilide. Bracketed L J intermediates and processes are proposed. R= -NC(C 4)...

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