Amino acids common precursor” pathway

Diagram 1. Common-precursor pathway for biosynthesis of the aromatic amino acids. The asterisk represents unknown intermediates. 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

The shikimate pathway is the major route in the biosynthesis of ubiquinone, menaquinone, phyloquinone, plastoquinone, and various colored naphthoquinones. The early steps of this process are common with the steps involved in the biosynthesis of phenols, flavonoids, and aromatic amino acids. Shikimic acid is formed in several steps from precursors of carbohydrate metabolism. The key intermediate in quinone biosynthesis via the shikimate pathway is the chorismate. In the case of ubiquinones, the chorismate is converted to para-hydoxybenzoate and then, depending on the organism, the process continues with prenylation, decarboxylation, three hydroxy-lations, and three methylation steps. - ... 

The proteinogenic amino acids (see p. 60) can be divided into five families in relation to their biosynthesis. The members of each family are derived from common precursors, which are all produced in the tricarboxylic acid cycle or in catabolic carbohydrate metabolism. An overview of the biosynthetic pathways is shown here further details are given on pp. 412 and 413. 

Alkaloids are generally classified by their common molecular precursors, based on the biological pathway used to construct the molecule. From a structural point of view, alkaloids are divided according to their shapes and origins. There are three main types of alkaloids (1) true alkaloids, (2) protoalkaloids and (3) pseudoalkaloids. True alkaloids and protoalkaloids are derived from amino acids, whereas pseudoalkaloids are not derived from these compounds (Table 1). 

Figure 9-4. Metabolism of the branched-chain amino acids. The first two reactions, transamination and oxidative decarboxylation, are catalyzed by the same enzyme in all cases. Details are provided only for isoleucine. Further metabolism of isoleucine and valine follows a common pathway to propionyl CoA. Subsequent steps in the leucine degradative pathway diverge to yield acetoacetate. An intermediate in the pathway is 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), which is a precursor for cytosolic cholesterol biosynthesis.

T Given that many amino acids are either neurotransmitters or precursors or antagonists of neutrotransmitters, genetic defects of amino acid metabolism can cause defective neural development and mental retardation. In most such diseases specific intermediates accumulate. For example, a genetic defect in phenylalanine hydroxylase, the first enzyme in the catabolic pathway for phenylalanine (Fig. 18-23), is responsible for the disease phenylketonuria (PKU), the most common cause of elevated levels of phenylalanine (hyperphenylalaninemia). 

Amino Acid Pathways Absent in Mammals Offer Targets for Safe Herbicides Chorismate Is a Common Precursor of the Aromatic Amino Acid Family... 

Cyanogenic glycosides are produced from a range of amino acids by a common pathway (Figure 7.49). The amino acid precursor of pranasin is phenylalanine, which is... 

Lysine.—Lysine is a common precursor of piperidine alkaloids. Of the two enantiomers of this amino-acid, the L-isomer is the more direct precursor, in plants, for piperidine alkaloids, e.g. anabasine, whereas D-lysine is more directly implicated in the biosynthesis of pipecolic acid (24)1,2,23 (cf Vol. 7, p. 7). It has now been shown that a pathway exists in the plant Nicotiana glauca,24 and also in the micro-organism Neurospora crassa2S which transforms D-lysine into L-lysine by way of L-pipecolic acid (24). 

The Krebs-citric acid cycle is the final common pathway for the oxidation of fuel molecules amino acids, fatty acids and carbohydrates. Most fuel molecules enter the cycle as a breakdown product, acetyl coenzyme A (acetyl CoA), which reacts with oxaloacetate (a four-carbon compound) to produce citrate (a six-carbon compound), which is then converted in a series of enzyme-catalysed steps back to oxaloacetate. In the process, two molecules of carbon dioxide and four energy-rich molecules are given off, and these latter are the precursors of the energy-rich molecule ATP, which is subsequently formed and which acts as the fuel source for all aerobic organisms. 

Proteins of all organisms are based on the 20 common amino acids, generally referred to as protein amino acids. In some cases, these amino acids are modified post-translationally, e.g. the hydroxyproline moieties in several cell wall proteins. Apart from these protein amino acids, numerous other amino acids occur in plants. Some of them are known to be intermediates in various pathways of primary metabolism, e.g. ornithine as a metabolite in arginine bios)m-thesis, 8-aminolevulinic acid as a precursor of chlorophyll and 0-acetylserine as an S-acceptor to yield cysteine. In addition, about 900 other amino acids, which are not thought to be involved in primary metabolism, have been isolated from plants. These non-protein amino acids (NPAAs) are regarded as typical secondary metabolites with corresponding ecological functions. 

Chapter 25 covers the biosynthesis of nucleotides, including the role of amino acids as biosynthetic precursors. A key evolutionary insight emphasized here is that many of the enzymes in these pathways are members of the same family and catalyze analogous chemical reactions. The focus on enzymes and reactions common to these biosynthetic pathways allows students to understand the logic of the pathways, rather than having to memorize a set of seemingly unrelated reactions. 

Traditional fermentation using microbial activity is commonly used for the production of nonvolatile flavor compounds such as acidulants, amino acids, and nucleotides. The formation of volatile flavor compounds via microbial fermentation on an industrial scale is still in its infancy. Although more than 100 aroma compounds may be generated microbially, only a few of them are produced on an industrial scale. The reason is probably due to the transformation efficiency, cost of the processes used, and our ignorance to their biosynthetic pathways. Nevertheless, the exploitation of microbial production of food flavors has proved to be successful in some cases. For example, the production of y-decalactone by microbial biosynthetic pathways lead to a price decrease from 20,000/kg to l,200/kg U.S. Generally, the production of lactone could be performed from a precursor of hydroxy fatty acids, followed by p-oxidation from yeast bioconversion (Benedetti et al., 2001). Most of the hydroxy fatty acids are found in very small amounts in natural sources, and the only inexpensive natural precursor is ricinoleic acid, the major fatty acid of castor oil. Due to the few natural sources of these fatty acid precursors, the most common processes have been developed from fatty acids by microbial biotransformation (Hou, 1995). Another way to obtain hydroxy fatty acid is from the action of LOX. However, there has been only limited research on using LOX to produce lactone (Gill and Valivety, 1997). 

Terpenoids do not necessarily contain exact multiples of five carbons and allowance has to be made for the loss or addition of one or more fragments and possible molecular rearrangements during biosynthesis. In reality the terpenoids are biosynthesized from acetate units derived from the primary metabolism of fatty acids, carbohydrates and some amino acids (see Fig. 2.10). Acetate has been shown to be the sole primary precursor of the terpenoid cholesterol. The major route for terpenoid biosynthesis, the mevalonate pathway, is summarized in Fig. 2.16. Acetyl-CoA is involved in the generation of the C6 mevalonate unit, a process that involves reduction by NADPH. Subsequent decarboxylation during phosphorylation (i.e. addition of phosphate) in the presence of ATP yields the fundamental isoprenoid unit, isopentenyl pyrophosphate (IPP), from which the terpenoids are synthesized by enzymatic condensation reactions. Recently, an alternative pathway has been discovered for the formation of IPP in various eubacteria and plants, which involves the condensation of glyceraldehyde 3-phosphate and pyruvate to form the intermediate 1-deoxy-D-xylulose 5-phosphate (Fig. 2.16 e.g. Eisenreich et al. 1998). We consider some of the more common examples of the main classes of terpenoids below. 

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