Aspartate 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. 

Although L-phenylalanine is a protein amino acid, and is known as a protein acid type of alkaloid precursor, its real role in biosynthesis (providing C and N atoms) only relates to carbon atoms. L-phenylalanine is a part of magic 20 (a term deployed by Crick in his discussion of the genetic code) and just for this reason should also be listed as a protein amino acid type of alkaloid precursor, although its duty in alkaloid synthesis is not the same as other protein amino acids. However, in relation to magic 20 it is necessary to observe that only part of these amino acids are well-known alkaloid precursors. They are formed from only two amino acid families Histidine and Aromatic and the Aspartate family . 

Fig. 2 Metabolic pathways in C. glutamicum for biosynthesis of the aromatic amino acids tryptophan, tyrosine, and phenylalanine (a) and amino acids belonging to the aspartate family including lysine, methionine, threonine, and isoleucine (b). Metabolic regulation by feedback inhibition is indicated by dotted lines...

THE ASPARTATE FAMILY Aspartate, the first member of the aspartate family of amino acids, is derived from oxaloacetate in a transamination reaction ... 

The aspartate family also contains asparagine, lysine, methionine, and threonine. Threonine contributes to the reaction pathway in which isoleucine is synthesized. The synthesis of isoleucine, often considered to be a member of the pyruvate family, is discussed on p. 467. 

The synthesis of the other members of the aspartate family (Figure 14.8) is initiated by aspartate kinase (often referred to as aspartokinase) in an ATP-requiring reaction in which the side chain carboxyl group is phosphorylated. Aspartate... 

Figure 18. Biosynthetic pathways for amino acids in the aspartate family. Circled Ps represent phosphate groups, POs. Pj represents inorganic phosphate, HPO/. [H] indicates reduction. T indicates transamination. Branch points and likely sites of isotopic fractionation are discussed in the text. In this and other reaction schemes, filled and open circles mark positions enriched or depleted in as a result of the source of the carbon flowing to that position. Upward and downward arrows mark positions likely to be enriched or depleted in C relative to precursor positions as a result of fractionations induced by isotope...

Miyajima, R. Shiio, I. Regulation of aspartate family amino acid biosynthesis in Brevibacterium flavum. V. Properties of homoserine kinase. J. Bio-chem., 71, 219-226 (1972)... 

Aspartate Family and Branched-Chain Amino Acids... 

Since the substrate specificity of individual aminotransferases may vary widely, it is not known whether the nitrogen atoms of the aspartate family and branched-chain amino acids are derived from a single, or from multiple precursors (Table I). Utilization of a common amino donor in aminotransferase catalyzed reactions would strengthen the biosynthetic relationship among the pathway products, whereas multiple precursors could tend to balance the synthesis of these amino acids with that of other protein precursors in a type of crosspathway or interfamily regulation. 

Fig. 1. Biosynthetic relationships among the aspartate family and branched-chain amino acids. Compounds which serve as branch point metabolites are bracketed and abbreviated as follows ASA, aspartate semialdehyde PHS, O-phosphohomoserine OlV, 2-oxoisovaierate. Each arrow represents an enzyme catalyzed reaction, and the details of the pathways for threonine, lysine, isoleucine, and valine, and leucine biosynthesis are presented in Figs. 2, 3, 4, and 5, respectively.

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). 

Aspartate Family and Branched>Chain Amino Adds... 

Fig. 7. Sequential control of the synthesis of the aspartate family of amino adds. Temporal control of the flow of carbon is illustrated by the successive Figs. 1-5. Potential quantitative changes in flow are approximated by the thickness of the solid arrows. As the concentration of an end product is increased (indicated by closed boxes), the pattern of synthesis is altered by utilization of negative (-) or positive (+) regulatory mechanisms as described in the text. The pattern of control which is illustrated assumes that aspartate kinase is sensitive to inhibition only by lysine. Variations of this pattern are discussed in the text.

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... 

The sequences of biochemical transformations involved in the synthesis of the aspartate family and branched-chain amino acids in multicellular plants are similar to those that occur in microorganisms. Support for this conclusion has been derived principally from isolation of a number of the requisite enzymes. Information on the kinetic and physical properties of enzymes is best achieved after extensive purification. In contrast, useful predictions of the physiological function of regulatory enzymes depend upon effective enzyme extraction and complete preservation of native properties. Since the latter objective has been emphasized during most investigations of enzymes associated with amino acid biosynthesis in plants, the bulk of our knowledge has been obtained from comparatively crude enzyme preparations. Results of both direct and competitive labeling experiments have added demonstrations of many of the predicted precursor-product relationships and a few metabolic intermediates have been isolated from plants. The nature of a number of intermediate reactions does, however, remain to be clarified notably, the reactions associated with the conversion of dihydropicolinate to lysine and those involved in the synthesis of leucine from 2-oxoisovalerate. 

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