Amino acid synthesis committed step

Figure 10.1. Schematic diagram showing inhibition of synthesis of amino acids a) single chain inhibition occurs when enzyme controlling committed step (S ) is inhibited by increasing concentrations of product AAj b) branched chain inhibition of by increased concentration of AA2 occurs at a post-branching step (sj), while permitting continued production of product of other branch (AAj). In general, each step is controlled by a single enzyme.

This three-step process for transferring fatty acids into the mitochondrion—esterification to CoA, transesterification to carnitine followed by transport, and transesterification back to CoA—links two separate pools of coenzyme A and of fatty acyl-CoA, one in the cytosol, the other in mitochondria These pools have different functions. Coenzyme A in the mitochondrial matrix is largely used in oxidative degradation of pyruvate, fatty acids, and some amino acids, whereas cytosolic coenzyme A is used in the biosynthesis of fatty acids (see Fig. 21-10). Fatty acyl-CoA in the cytosolic pool can be used for membrane lipid synthesis or can be moved into the mitochondrial matrix for oxidation and ATP production. Conversion to the carnitine ester commits the fatty acyl moiety to the oxidative fate. 

Consider, for example, the biosynthesis of the amino acids valine, leucine, and isoleucine. A common intermediate, hydroxy ethyl thiamine pyrophosphate (hydroxy ethyl-TPP Section 17.1.1). initiates the pathways leading to all three of these amino acids. Hydroxyethyl-TPP can react with a-ketobutyrate in the initial step for the synthesis of isoleucine. Alternatively, hydroxyethyl-TPP can react with pyruvate in the committed step for the pathways leading to valine and leucine. Thus, the relative concentrations of a-ketobutyrate and pyruvate determine how much isoleucine is produced compared with valine and leucine. Threonine deaminase, the PLP enzyme that catalyzes the formation of a-ketobutyrate, is allosterically inhibited by isoleucine (Figure 24.22). This enzyme is also allosterically activated by valine. Thus, this enzyme is inhibited by the product of the pathway that it initiates and is activated by the end product of a competitive pathway. This mechanism balances the amounts of different amino acids that are synthesized. 

The cell achieves its efficiency, stability, and responsiveness through the use of metabolic pathways. A metabolic pathway is a sequence of enzyme-catalyzed reactions in which the product of one reaction is the substrate for the next. Usually, a pathway ends with the production of a particular product, such as an amino acid needed for protein synthesis. A particular starting material, such as glucose, may be used for a variety of purposes. In this case, the metabolic pathways have an initial section that is common to each purpose eventually, each pathway splits off into its own section. At this point, a key enzyme controls the flow of substrate into the specific section of the pathway. This enzyme is controlled allosterically, typically by a product of the pathway, in a negative feedback loop, as described below. This first step on a unique pathway is called the committed step or committed reaction. 

The a-oxoamine synthases family is a small group of fold-type I enzymes that catalyze Claisen condensations between amino acids and acyl-CoA thioesters (Figure 16). Members of this family are (1) 8-amino-7-oxononanoate (AON) synthase (AONS), which catalyzes the first committed step in the biosynthesis of biotine, (2) 5-aminolevulinate synthase (ALAS), responsible for the condensation between glycine and succinyl-CoA, which yields aminolevulinate, the universal precursor of tetrapyrrolic compounds, (3) serine palmitoyltransferase (SPT), which catalyzes the first reaction in sphingolipids synthesis, and (4) 2-amino-3-ketobutyrate CoA ligase (KBL), involved in the threonine degradation pathway. With the exception of the reaction catalyzed by KLB, all condensation reactions involve a decarboxylase step. 

Figure 9. ArsC and y-ECS catalyzed reactions. The bacterial arsenate reductase (ArsC) catalyzes the electrochemical reduction of arsenate to arsenite. The bacterial y-glutamylcysteine synthetase (y-ECS) catalyzes the formation of y-glutamylcysteine (y-EC) from the amino acids glutamate and cysteine and is the committed step in the synthesis of glutathione (GSH) and phytochelatins, PCs (indicated by three arrows). Reduced arsenite can bind organic thiols (RS) such as those in y-EC, GSH, and PCs through the replacement of oxygen by organic sulfttr species.

Transcripts that encode all of the enzymes involved in the biosynthesis of vitamin E are elucidated in Table 18.2. The identified enzymes used to reconstruct the pathway of vitamin E bios5mthesis are presented in Fig. 18.3. The vitamin E biosynthetic pathway in D. tertiolecta is similar to that of the plant AraUdopsis thaliana, and the cyanobacterium Synecho-cystis sp. D. tertiolecta utilizes the metabolism of the aromatic amino acid tyrosine for the s5mthesis of the polar head group, whereas the unsaturated tail is derived from phytyl-pyrophosphate (PPP), which is a metabolite of terpenoid backbone biosynthesis (DellaPenna and Pogson, 2006). The committed step in the synthesis of the head group is catalyzed by the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27), which converts... 

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