Pyruvate amino acid family

Amino Acid Biosynthesis Aromatic amino acid family Aspartate family Glutamate family Pyruvate family Serine family Histidine family Other... 

Non-essential amino acids are those that arise by transamination from 2-oxoacids in the intermediary metabolism. These belong to the glutamate family (Glu, Gin, Pro, Arg, derived from 2-oxoglutarate), the aspartate family (only Asp and Asn in this group, derived from oxaloacetate), and alanine, which can be formed by transamination from pyruvate. The amino acids in the serine family (Ser, Gly, Cys) and histidine, which arise from intermediates of glycolysis, can also be synthesized by the human body. 

Sulfate Must Be Reduced to Sulfide before Incorporation into Amino Acids The Aspartate and Pyruvate Families Both Make Contributions to the Synthesis of Isoleucine... 

Outline of the biosynthesis of the 20 amino acids found in proteins. The de novo biosynthesis of amino acids starts with carbon compounds found in the central metabolic pathways. The central metabolic pathways are drawn in black, and the additional pathways are drawn in red. Some key intermediates are illustrated, and the number of steps in each pathway is indicated alongside the conversion arrow. All common amino acids are emphasized by boxes. Dashed arrows from pyruvate to both diaminopimelate and isoleucine reflect the fact that pyruvate contributes some of the side-chain carbon atoms for each of these amino acids. Note that lysine is unique in that two completely different pathways exist for its biosynthesis. The six amino acid families are screened. 

The aspartate (oxaloacetate) family of amino acids includes aspartate, asparagine, methionine, lysine, threonine, and isoleucine (see fig. 21.1). The pyruvate family includes alanine, valine, leucine, and also lysine and isoleucine (see fig. 21.1). Threonine is a precursor of isoleucine. It is converted into isoleucine by a group of enzymes that are also used in the synthesis of valine (fig. 21.10). 

The aspartate and pyruvate families together contain 11 amino acids. Because of the reactions involved in its synthesis, isoleucine is considered a member of both families. Isoleucine and valine use four enzymes in common in their biosynthetic pathways. 

GOT is a 90-kDa, homodimeric enzyme that catalyzes the reversible transfer of an amino group from aspartate to a-ketoglutarate (Fig. 8-1). Ox-aloacetate and glutamate are the products of this reaction. GOT is one member of the family of transaminase enzymes. All members of this family catalyze the transfer of an amino group from an amino acid to an a-keto acid, which is nearly always a-ketoglutarate or pyruvate. In the process,... 

Vitamins are required in the diet for groMh, maintenance, and reproduction. These qualities are shared by other nutrients, such as the amino adds and the minerals- Why are amino acids and minerals not called vitamins The vitamins share a family of characteristics. They are organic compounds required in the diet in only smaii amounts They are not catabolized to satisfy part of the energy requirement and are not used for structural purposes. Many vitamins are used as cofactors for enzymes. Pyruvate dehydrogenase is one striking example. This enzj me uses five cofactors, where four of these cofactors are derived from vitamins-... 

While each of the five LDH isoenzymes catalyzes the conversion of lactic acid to pyruvic acid, the isoenzymes are produced in different organs. Because of this, the polypeptide moieties and the rates at which lactate can be converted to pyruvate are slightly different for each isoenzyme. Similarly, different species often possess identical metabolic pathways, and have equivalent but slightly different enzymes that catalyze identical reactions. The differences that occur within such a family of enzymes usually occur in noncritical regions of the polypeptide moiety, by the substitution of one amino acid residue for another, or by the deletion of amino acid residues. 

On the basis of the similarities in their synthetic pathways, the amino acids can be grouped into six families glutamate, serine, aspartate, pyruvate, the aromatics, and histidine. The amino acids in each family are ultimately derived from one precursor molecule. In the discussions of amino acid synthesis that follow, the intimate relationship between amino acid metabolism and several other metabolic pathways is apparent. Amino acid biosynthesis is outlined in Figure 14.4. 

On the basis of the biochemical pathways in which they are synthesized, the amino acids can be divided into six families glutamate, serine, aspartate, pyruvate, aromatics, and histidine. 

The a-ketoglutarate dehydrogenase complex is one of a three-member family of similar a-keto acid dehydrogenase complexes. The other members of this family are the pyruvate dehydrogenase complex, and the branched chain amino acid a-keto acid dehydrogenase complex. Each of these complexes is specific for a different a-keto acid structure. In the seqnence of reactions catalyzed by the complexes, the a-ketoacid is decarboxylated (i.e., releases the carboxyl gronp as CO2) (Fig.20.8). The keto gronp is oxidized to the level of a carboxylic acid, and then combined with CoASH to form an acyl CoA thioester (e.g., succinyl CoA). 

Classification of amino acids into biosynthetic families emphasizes the common origin of related metabolites and is conceptually useful in delineating regulatory relationships. Lysine, threonine, methionine, and isoleucine comprise a family of amino acids originating with aspartate. However, isoleucine is also structurally and metabolically related to the branched-chain amino acids, leucine and valine. The latter two amino acids, along with alanine, are members of the pyruvate family. The common metabolic pre-... 

An alternative approach to estimating the metabolic capabilities of chloroplasts entails measurement of the light-dependent metabolism of radioactive tracers. Using isolated pea chloroplasts. Mills and Wilson (1978a) found that lysine, methionine, threonine, and isoleucine were synthesized from [ C]aspartate. Further evidence that aspartate was being metabolized via the anticipated pathways was provided by the demonstration that the synthesis of homoserine was inhibited by lysine and threonine (Lea et al., 1979). These results, combined with those relating to enzyme localization, lead to the concept that chloroplasts contain a complete functional sequence of enzymes which can facilitate the synthesis of the aspartate family and at least some of the branched-chain amino acids. This is consistent with the importance of chloroplasts in ammonia assimilation (Miflin and Lea, this volume. Chapter 4) and with the evidence that protein can be synthesized from CO2 in isolated plastids (Shepard and Leven, 1972 Huberer al., 1977). The actual fraction of [ ]02 which is utilized for amino acid biosynthesis in isolated plastids is usually quite small. Thus, reactions which normally occur outside of chloroplasts are considered to be of major importance in the synthesis of carbon skeletons such as oxaloacetate or pyruvate (Kirk and Leech, 1972 Leech and Murphy, 1976). 

Regulation of the synthesis of the branched-chain amino acids, like that of the aspartate family, can be viewed in a temporal framework (Fig. 8). However, the nature of the controls associated with the pathway enzymes do not necessarily suggest an obligatory sequence of regulatory interactions. The sequence illustrated in Fig. 8 assumes that each of the end-products would initially be synthesized from its respective precursors. As isoleucine biosynthesis is reduced by inhibition of threonine dehydratase, the competition between pyruvate and 2-oxobutyrate for the active site of acetohydroxyacid synthase would be diminished. This could result in an increased rate of synthesis of leucine and valine (Fig. 8, 2). Leucine would eventually inhibit isopropylmalate synthase and, to a lesser extent, acetohydroxyacid synthase (Fig. 8, 3). The reduced flow of carbon through the pathway would be utilized for the synthesis of valine. As the concentration of valine increased, the activity of acetohydroxyacid synthase would be sharply curtailed due to... 

Fig.3. Amino acids. The pyruvate family of amino acids...

Lysine belongs to the aspartate family of amino acids including homoserine, methionine, isoleucine, and threonine. It is formed from pyruvate, oxaloacetate, and... 

Phosphoenol pyruvate carboxykinase and pyruvate carboxylase are the major anaple-rotic enzymes supplying the precursor for the aspartate family of amino acids. Engineering of these two enzymes resulted in redirecting the anaplerotic flux toward the amino... 

Further metabolism of amino acids produced by transamination results in the formation of biogenetically related families of amino acids. Thus the pyruvate family comprises alanine, leucine and valine and similar families are based upon aspartic and glutamic acids and serine. 

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