Metabolic sequence, initiated

Metabolic control can be understood to some extent by focusing attention on those enzymes that catalyze rate-limiting steps in a reaction sequence. Such pacemaker enzymes1-4 are often involved in reactions that determine the overall respiration rate of a cell, reactions that initiate major metabolic sequences, or reactions that initiate branch pathways in metabolism. Often the first step in a unique biosynthetic pathway for a compound acts as the pacemaker reaction. Such a reaction may be described as the committed step of the pathway. It usually proceeds with a large decrease in Gibbs energy and tends to be tightly controlled. Both the rate of synthesis of the enzyme protein and the activity of the enzyme, once it is formed, may be inhibited by feedback inhibition which occurs when an end product of a biosynthetic pathway accumulates... 

The reduction of aromatic nitro and azo xenobiotics leads to aromatic primary amine metabolites. Aromatic nitro compounds are reduced initially to the nitroso and hydroxyl-amine intermediates, as shown in the following metabolic sequence ... 

To support metabolic studies, there is an option to restrict the growth of reaction sequences to products containing a specified, radio labeled atom. There is also an option to construct a very large metabolic tree initially and then to prune it automatically to show only branches that lead to structures with specified molecular formulas coming from mass spectrometric studies. 

Vomiting of gastric contents. A common example occurs in the vomiting of gastric contents, which results in the loss of hydrogen ions. When the vomiting is mild to moderate, the metabolic alkalosis initiates the sequence of events which you followed in section A3. 

Because the generation of C02 from [l- Cjglucose is a measure of pentose phosphate activity, the initiating step in the P5C-mediated metabolic sequence, it was used as the metabolic endpoint of parametabolic regulation. When hepatocytes or erythrocytes were incubated separately, proline had no effect on pentose phosphate activity in either cell and in the absence of proline the total activity in coincubations was the... 

Norcocaine 2, the demethylated metabolite of cocaine 1, is detected soon after administration of the parent drug. This transformation be the initial step in a metabolic sequence leading to the observed toxicity. Microsomes in the liver and brain further oxidize 2 to the. nitroxide which may be intimately involved in a variety of free... 

Fatty acids with odd numbers of carbon atoms are rare in mammals, but fairly common in plants and marine organisms. Humans and animals whose diets include these food sources metabolize odd-carbon fatty acids via the /3-oxida-tion pathway. The final product of /3-oxidation in this case is the 3-carbon pro-pionyl-CoA instead of acetyl-CoA. Three specialized enzymes then carry out the reactions that convert propionyl-CoA to succinyl-CoA, a TCA cycle intermediate. (Because propionyl-CoA is a degradation product of methionine, valine, and isoleucine, this sequence of reactions is also important in amino acid catabolism, as we shall see in Chapter 26.) The pathway involves an initial carboxylation at the a-carbon of propionyl-CoA to produce D-methylmalonyl-CoA (Figure 24.19). The reaction is catalyzed by a biotin-dependent enzyme, propionyl-CoA carboxylase. The mechanism involves ATP-driven carboxylation of biotin at Nj, followed by nucleophilic attack by the a-carbanion of propi-onyl-CoA in a stereo-specific manner. 

Xanthobacter sp. strain Py2 may be grown with propene or propene oxide. On the basis of amino acid sequences, the monooxygenase that produces the epoxide was related to those that catalyzes the monooxygenation of benzene and toluene (Zhou et al. 1999). The metabolism of the epoxide is initiated by nucleophilic reaction with coenzyme M followed by dehydrogenation (Eigure 7.13a). There are alternative reactions, both of which are dependent on a pyridine nucleotide-disulfide oxidoreductase (Swaving et al. 1996 Nocek et al. 2002) ... 

This arrangement of subgroups is due to the hypothetical biosynthetic sequence. It assumes that precursors for these alkaloids are the Af-methylphth-alideisoquinolinium salts, whose presence in plants is well documented. Enol lactones may be the initial degradation products formed in a Hofmann-type jft-elimination process. They could be hydrated to the keto acids and in the next step oxidated in air to the diketo acids. Diketo adds may undergo further oxidative cleavage to yield simple alkaloids of the fumariflorine (87) type 85,86), which seem to be the final products of the metabolism of phthalideiso-quinoline alkaloids. 

The Krebs cycle will only operate when the hydrogen atoms and electrons produced in the cycle enter the electron transfer chain, ultimately to react with oxygen that is, the two processes must take place simultaneously. A metabolic pathway is defined as a sequence of reactions that is initiated by a flux-generating step. In the cycle, citrate synthase catalyses the flux-generating reaction (Table 9.2) but there is no such reaction in the electron-transfer chain. Consequently, the cycle can be considered to be the first part of a longer pathway, which includes the electron transfer chain (Figure 9.3). 

Certain foods can trigger a migraine attack by effects on neurotransmitter release or metabolism in the brain. For example, a number of foods contain tryptamine which is known to cause release of other amines (dopamine, noradrenaline and 5-hydroxytryptamine) from both nerve terminals and platelets. This release could initiate the sequence of events that results in the migraine attack. Elimination of such foods from the diet can decrease the number of headaches. Compounds that discourage platelet aggregation (e.g. aspirin) may prevent such attacks. 

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