Keto acids, organic molecules

Mineral nitrogen in any form accepted by plants cannot be directly incorporated into proteins, however, it needs first to be transformed via keto acids into molecules of amino acids. All these processes are anabolic and endothermic and thus, they require energy, which is mainly released by the oxidation of organic substances produced during photosynthesis and CO2 assimilation. 

Recently, bacterial NRPS modules with the organization of A-KR-PCP have been discovered in the valino-mycin and cereulide synthetases. The A domains of these modules selectively activate a-keto acids. After the resulting adenylate is transferred to the PCP domain, the a-ketoacyl- -PCP intermediate is reduced to a PCP-bound, a-hydroxythioester by the KR domain. These domains use NAD(P)H as a cofactor and are inserted into A domains between two conserved core motifs analogous to MT domains. Their substrate specificity differs from that of polyketide synthase KR domains, which reduce /3-ketoacyl substrates. Similar fungal NRPSs, such as beauvericin synthetase, utilize A domains that selectively activate a-hydroxy acids. These molecules are thought to be obtained using an in trans KR domain, which directly reduces the necessary, soluble a-keto acid. 

We ll see in Chapter 29 that living organisms use many of the same tions that chemists use in the laboratory. This is particularly true of i bonyl-group reactions, where nucleophilic addition steps play a critical ruie in the biological synthesis of many vital molecules. For example, one of the pathways by which amino acids are made involves nucleophilic addition of an amine to w-keto acids. To choo.se a specific example, the bacterium Bari/ lus subtilis synthesizes the amino acid alanine from pyruvic acid. 

A polyfunctional organic molecule can contain many different kinds of functional groups, but for nomenclature purposes, we must choose just one suffix. It s not correct to use two sufhxes. Thus, keto ester 3 must be named either as a ketone with an -one. suffix or as an ester with an -oate suffix but can t be named as an -onoate. Similarly, amino alcohol 4 must be named either as an alcohol (-ol) or as an amine i-amine) but can t properly be named as an -olamine. The only exception to this rule is in naming compounds that have double or triple bonds. For example, the unsaturated acid H2C=CHCH2C00H is 3-butenoic acid, and the acetylenic alcohol HCSCCH2CH2CH2CH2OH is 5-hexyn-l-ol. 

Most CO2 assimilation takes place at a- and 8-carbons of carbonyl groups of organic molecules to give a-hydroxy-, a-keto, and )8-keto acids 90, 91). There has been no report of a-hydroxyketo acid formation by artificial CO2 fixation with the intention to mimic CO2 assimilation in green plants, in which two moles of 3-phosphoglycerate (PGA) are produced hy CO2 fixation to ribulose-l,5-bisphosphate(RuDP) ... 

Because transamination reactions are reversible, it is theoretically possible for all amino acids to be synthesized by transamination. However, experimental evidence indicates that there is no net synthesis of an amino acid if its a-keto acid precursor is not independently synthesized by the organism. For example, alanine, aspartate, and glutamate are nonessential for animals because their a-keto acid precursors (i.e., pyruvate, oxaloacetate, and a-ketoglutarate) are readily available metabolic intermediates. Because the reaction pathways for synthesizing molecules such as phenylpyruvate, a-keto-/Thydroxybutyrate, and imidazolepyruvate do not occur in animal cells, phenylalanine, threonine, and histidine must be provided in the diet. (Reaction pathways that synthesize amino acids from metabolic intermediates, not only by transamination, are referred to as de novo pathways.)... 

DIRECT INCORPORATION OF AMMONIUM IONS INTO ORGANIC MOLECULES There are two principal means by which ammonium ions are incorporated into amino acids and eventually other metabolites (1) reductive amination of a-keto acids and (2) formation of the amides of aspartic and glutamic acid with subsequent transfer of the amide nitrogen to form other amino acids. 

This may undergo reduction to the corresponding add, a-keto valeric acid, or may be decarboi lated to an aldehyde, which then reacts with another molecule of pyruvic acid to form a 7-carbon acid. By a continuation of this process, fatty acids of increasing length can be assembled. Intermediate reactants such as these have not been foimd as yet in animal tissues, but the fact that milk fat contains a variety of lower members of the aliphatic series su ests that fat construction in the organism is by such stages. The preferential occurrence in nature of fatty acids containing an even total number of carbon atoms is explained by the decarboxylation and subsequent terminal oxidation of the antecedent keto acid. 

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