Amino acid carbon skeleton

Early investigators grouped alkaloids according to the plant families in which they are found, the stmctural types based on their carbon framework, or their principal heterocycHc nuclei. However, as it became clear that the alkaloids, as secondary metaboUtes (30—32), were derived from compounds of primary metabohsm (eg, amino acids or carbohydrates), biogenetic hypotheses evolved to link the more elaborate skeletons of alkaloids with their simpler proposed pregenitors (33). These hypotheses continue to serve as valuable organizational tools (7,34,35). 

Amino group An -NH2 group attached to a carbon skeleton as in the amines and amino acids. 

One class of enzymes that follow a ping-pong-type mechanism are aminotransferases (previously known as transaminases). These enzymes catalyze the transfer of an amino group from an amino acid to an a-keto acid. The products are a new amino acid and the keto acid corresponding to the carbon skeleton of the amino donor ... 

A rather limited collection of simple precursor molecules is sufficient to provide for the biosynthesis of virtually any cellular constituent, be it protein, nucleic acid, lipid, or polysaccharide. All of these substances are constructed from appropriate building blocks via the pathways of anabolism. In turn, the building blocks (amino acids, nucleotides, sugars, and fatty acids) can be generated from metabolites in the cell. For example, amino acids can be formed by amination of the corresponding a-keto acid carbon skeletons, and pyruvate can be converted to hexoses for polysaccharide biosynthesis. 

Figure 9.3. Percentage of non-detectable amino acids in collagen extracts from archaeological human skeletons. Numbers on top of the columns indicate number of carbon atoms per amino acid. XW = weighted mean of % loss (cf. text). Only high-carbon amino acids are more frequently lost than the average.

The intramolecular cycloaddition of munchnone intermediates (derived from the cyclodehydration of A-acyl amino acids) with 1,3-dipolarophiles was employed to construct the mitomycin skeleton. Thus, heating alkynyl acids 23 with acetic anhydride forms the intermediates 24 which undergo cyclization with loss of carbon dioxide to afford the 4-oxo-tetrahydroindoles 25 <96TL2887>... 

The amino acids are required for protein synthesis. Some must be supplied in the diet (the essential amino acids) since they cannot be synthesized in the body. The remainder are nonessential amino acids that are supplied in the diet but can be formed from metabolic intermediates by transamination, using the amino nitrogen from other amino acids. After deamination, amino nitrogen is excreted as urea, and the carbon skeletons that remain after transamination (1) are oxidized to CO2 via the citric acid cycle, (2) form glucose (gluconeogenesis), or (3) form ketone bodies. 

Glucose provides carbon skeletons for the glycerol moiety of fat and of several nonessential amino acids. 

Aminotransferase (transaminase) reactions form pymvate from alanine, oxaloacetate from aspartate, and a-ketoglutarate from glutamate. Because these reactions are reversible, the cycle also serves as a source of carbon skeletons for the synthesis of these amino acids. Other amino acids contribute to gluconeogenesis because their carbon skeletons give rise to citric acid cycle... 

The citric acid cycle is amphibolic, since in addition to oxidation it is important in the provision of carbon skeletons for gluconeogenesis, fatty acid synthesis, and interconversion of amino acids. 

Cysteine, tyrosine, and hydroxylysine are formed from nutritionally essential amino acids. Serine provides the carbon skeleton and homocysteine the sulfur for cysteine biosynthesis. Phenylalanine hydroxylase converts phenylalanine to tyrosine. 

Other than a nutritional role linked to mineralization processes, humic compounds have been hypothesized to directly affect plant nutrition, since it has been suggested that roots may take up low-molecular-weight humic molecules (21). Interestingly, plants have been ob.served to express carriers for amino acids (22) and small peptides (23) at the root level. Certain components of the humic fraction have been found inside root cells and were, moreover, translocated to the shoots (24,25). Recent experiments performed on rice cells in suspension culture seem to suggest that they may use carbon skeletons from humic molecules to synthesize proteins and DNA (26). 

Three compounds acetoacetate, P-hydroxybutyrate, and acetone, are known as ketone bodies. They are suboxidized metabolic intermediates, chiefly those of fatty acids and of the carbon skeletons of the so-called ketogenic amino acids (leucine, isoleucine, lysine, phenylalanine, tyrosine, and tryptophan). The ketone body production, or ketogenesis, is effected in the hepatic mitochondria (in other tissues, ketogenesis is inoperative). Two pathways are possible for ketogenesis. The more active of the two is the hydroxymethyl glutarate cycle which is named after the key intermediate involved in this cycle. The other one is the deacylase cycle. In activity, this cycle is inferior to the former one. Acetyl-CoA is the starting compound for the biosynthesis of ketone bodies. 

One of the sex pheromone components of the housefly, Musca domestica, is Z9-21 H that is found on the cuticular surface of the fly. This compound is formed by the elongation of Z9-18 CoA using malonyl-CoA and NADPH to Z15-24 CoA which is decarboxylated to form Z9-21 Hc (Fig. 3) [78-80]. Other pheromone components include an epoxide and ketone that are produced from Z9-21 Hc by a cytochrome P450 [81,82] and methyl-branched alkanes that are produced by the substitution of methylmalonyl-CoA in place of malonyl-CoA at specific points during chain elongation [83,84]. A novel microsomal fatty acid synthase is involved in production of methyl-branched alkanes in most insects [85-87]. This fatty acid synthase is different from the ubiquitous soluble fatty acid synthase that produces saturated straight chain fatty acids in that it is found in the microsomes and prefers methylmalonyl-CoA. The amino acids valine and isoleucine can provide the carbon skeletons for methylmalonyl-CoA as well as propionate [83]. 

It should be emphasized that citric acid is not the only possible acid employed in Pechini-type syntheses. Other polybasic carboxylic hydroxy acids (malic, tartaric, hydroxyglutaric, etc.) and polybasic carboxylic acids (e.g., succinic) have been probed in Refs. [4, 13-16], As far as amino acids are concerned, glycine seems to remain the only representative [13, 14]. However, the choice of each particular organic acid has never been justified, and no comparative studies are performed in order to find possible dependencies of the process (ability to form a sol, a gel, or a resin, easiness of thermal decomposition of precursors, etc.) on the steric factors, specifically, on the number of hydroxy and carboxylic groups in the molecule of an acid, as well as on the length of its carbon skeleton. 

Replacement of the hydroxyl group on the phenyl ring with a carboxyl group forms a molecule of benzoic acid. Addition of a hydroxyl at the 2-position on a benzoic acid molecule forms 2-hydroxybenzoic acid or salicylic acid. The slightly more complex phenylpropanoid skeleton contains a linear three-carbon chain (the propanoic group) added to the benzene ring (the phenyl group). Addition of ammonia to carbon 2 of this three-carbon side chain yields the amino acid phenylalanine (Fig. 3.3). Phenylalanine... 

Reaction of the thia-amino acid 392 with trifluoroacetic anhydride gave the 2,2,2-trifluoro-l-[7-(trifluoromethyl)-l//-pyrrolo[l,2-c]-[l,3]thiazol-6-yl] ethanone pyrrole 395. The formation of the pyrrole can be rationalized by a sequence involving trifluoroacetylation of the enamine 392 affording dione 393 followed by loss of water and carbon dioxide to give the aromatic product 395. These decarboxylations afford fluorinated derivatives of heterocyclic skeletons known to exhibit interesting biological activity (Scheme 58) <2000T7267>. 

GNG from the carbon skeletons of glucogenic amino acids and lactate... 

Following their deamination, several amino acids can be converted into oxaloacetate via pyruvate or other components of the TCA cycle these are termed glucogenic amino acids because their carbon atoms may eventually appear in glucose (see Table 6.7). The carbon skeletons of other amino acids may be converted into acetyl-CoA or acetoacetyl-CoA and these are ketogenic amino acids. A few amino acids be metabolized through both glucogenic and ketogenic pathways. 

As we have seen, normally pyruvate would be the substrate for pyruvate dehydrogenase complex to form acetyl-CoA, but during fasting in the absence of glucose, acetyl -CoA for the TCA cycle is derived from fatty acid (3-oxidation (see Section 7.5.2) so pyruvate is diverted into oxaloacetate by the enzyme pyruvate carboxylase. Thus any amino acids whose carbon skeletons can be converted into pyruvate, OAA or another substrate of the TCA cycle, can be used for glucose synthesis. 

The calorific capacity of amino acids is comparable to that of carbohydrates so despite their prime importance in maintaining structural integrity of cells as proteins, amino acids may be used as fuels especially during times when carbohydrate metabolism is compromised, for example, starvation or prolonged vigorous exercise. Muscle and liver are particularly important in the metabolism of amino acids as both have transaminase enzymes (see Figures 6.2 and 6.3 and Section 6.4.2) which convert the carbon skeletons of several different amino acids into intermediates of glycolysis (e.g. pyruvate) or the TCA cycle (e.g. oxaloacetate). Not all amino acids are catabolized to the same extent... 

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