Decarboxylation biological example

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

In this type of spin traps, 5,5-dimethyl-l-pyrroline-Af-oxide (DMPO) deserves particular mention. DMPO is widely employed as a spin trap in the detection of transient radicals or ion-radicals in chemical and biological systems (see, e.g., Siraki et al. 2007). Characteristic ESR spectra arising from the formation of spin adducts are used for identification of specific spin species. In common opinion, such identification is unambiguous. However, in reactions with superoxide ion (Villamena et al. 2004, 2007b), carbon dioxide anion-radical (Villamena et al. 2006), or carbonate anion-radical (Villamena et al. 2007a), this spin trap gives rise to two adducts. Let us consider the case of carbonate anion-radical. The first trapped product arises from direct addition of carbonate anion-radical, second adduct arises from partial decarboxylation of the first one. Scheme 4.25 illustrates such reactions based on the example of carbonate anion-radical. 

True alkaloids derive from amino acid and they share a heterocyclic ring with nitrogen. These alkaloids are highly reactive substances with biological activity even in low doses. All true alkaloids have a bitter taste and appear as a white solid, with the exception of nicotine which has a brown liquid. True alkaloids form water-soluble salts. Moreover, most of them are well-defined crystalline substances which unite with acids to form salts. True alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as N-oxides. These alkaloids occur in a limited number of species and families, and are those compounds in which decarboxylated amino acids are condensed with a non-nitrogenous structural moiety. The primary precursors of true alkaloids are such amino acids as L-ornithine, L-lysine, L-phenylalanine/L-tyrosine, L-tryptophan and L-histidine . Examples of true alkaloids include such biologically active alkaloids as cocaine, quinine, dopamine, morphine and usambarensine (Figure 4). A fuller list of examples appears in Table 1. 

A number of naturally occurring compounds with a disulfide unit have shown interesting biological activity [28, 29]. Nereistoxin, charatoxin, asparagusic acid, a plant growth inhibitor, and lipoic acid, a key co-factor in the oxidative decarboxylation of pyruvate, are examples taken in the 1,2-dithiolan series. 

Aldolases such as fructose-1,6-bisphosphate aldolase (FBP-aldolase), a crucial enzyme in glycolysis, catalyze the formation of carbon-carbon bonds, a critical process for the synthesis of complex biological molecules. FBP-aldolase catalyzes the reversible condensation of dihydroxyacetone phosphate (DHAP) and glyceralde-hyde-3-phosphate (G3P) to form fructose-1,6-bisphosphate. There are two classes of aldolases the first, such as the mammalian FBP-aldolase, uses an active-site lysine to form a Schiff base, whereas the second class features an active-site zinc ion to perform the same reaction. Acetoacetate decarboxylase, an example of the second class, catalyzes the decarboxylation of /3-keto acids. A lysine residue is required for good activity of the enzyme the -amine of lysine activates the substrate carbonyl group by forming a Schiff base. 

Aromatic polyketides are structurally diverse, often polycyclic molecules that are derived from unreduced polyketone chains. This group of compounds is produced with the help of type II polyketide synthase (PKS), a complex of enzymes that catalyzes the iterative decarboxylative condensation of malonyl-CoA extender units with an acyl starter unit [70], The carbon framework of aromatic polyketides is further decorated with different functionalities, and carbohydrates are often one of them. Their presence has profound effects on physico-chemical and biological properties of aromatic polyketides. For example, anthracycline aglycones are stable and unpolar, while polyglycosylated anthracyclines are quite polar and often... 

It is clear that biological systems can manage the chemical reactivity of unstable species. For example, oxalo-acetate—a metabolic intermediate in terran metabolism that is a precursor of citric acid, malic acid, and the amino acid aspartic acid—decarboxylates readily, with a half-life measured in minutes at room temperature at neutral pH. The half-life for the decarboxylation of oxaloacetate drops to seconds at high temperatures in pure water. It is not clear how microorganisms that live at high temperatures manage the instability of oxaloacetate, which is a key intermediate in standard biochemistry for the formation of amino acids, such as aspartate, and asparagine. 

Table 6.1 lists the water-soluble vitamins with their structures and coenzyme forms. Certain portions of the coenzymes are especially important in their biological activities, and they are indicated by arrows. For example, in case of coenzyme A, a thiol ester is formed between its -SH residue and the acyl group being transferred. And in the case of pyridoxal phosphate, its carbonyl residue forms a Schiff base with the amino group of the amino acid that is being decarboxylated. Fat-soluble vitamins (Table 6.2) are also transformed into biologically active substances. However, with the possible exception of vitamin K, these do not operate as prosthetic groups or cosubstrates in specific enzyme reactions. 

The interest in the mechanisms of SchifF base hydrolysis stems largely from the fact that the formation and decomposition of SchifF base linkages play an important role in a variety of enzymatic reactions, for example, carbonyl transfers involving pyridoxal phosphate, aldol condensations, /3-decarboxylations and transaminations. The mechanisms for the formation and hydrolysis of biologically important SchifF bases, and imine intermediates, have been discussed by Bruice and Benkovic (1966) and by Jencks (1969). As the consequence of a number of studies (Jencks, 1959 Cordes and Jencks, 1962, 1963 Reeves, 1962 Koehler et al., 1964), the mechanisms for the hydrolysis of comparatively simple SchifF bases are reasonably well understood. From the results of a comprehensive kinetic investigation, the mechanisms for the hydrolysis of m- and p-substituted benzylidine-l,l-dimethylethylamines in the entire pH range (see, for example, the open circles in Fig. 13) have been discussed in terms of equations (23-26) (Cordes and Jencks, 1963) ... 

The properties of phenolic lipids have tended to be dominated by technological aspects and it is only comparatively recently that potential biological usefulness has come to the fore. For example, products derived from the Anacardiacae occidentale, notably cardanol obtained by semisynthesis through thermal decarboxylation were all directed to polymeric and technical applications and the vast industrial literature [246] contains only two references to insecticidal uses of chlorinated cardanol [247]. 

An example of a decarboxylation that occurs in biological systems is the decarboxylation of acetoacetate. Acetoacetate decarboxylase, the enzyme that catalyzes the reaction, first forms an imine with acetoacetate. The imine is protonated under physiological conditions... 

The imidazole molecule is incorporated into many biologically relevant molecules. For example, the amino acid histidine is present in proteins and enzymes, while histamine (its decarboxylated product) is important in the body s immune response system. The imidazole ring has been found in a number of natural products, particularly the oroidin-derived alkaloids. One of the structurally simple compounds in this class of natural products is girolline, containing a 2-amino-imidazole attached to a chlorohydrin moiety. ... 

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