Deamination citric acid cycle

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. 

The citric acid cycle is not only a pathway for oxidation of two-carbon units—it is also a major pathway for interconversion of metabolites arising from transamination and deamination of amino acids. It also provides the substtates for amino acid synthesis by transamination, as well as for gluconeogenesis and fatty acid synthesis. Because it fimctions in both oxidative and synthetic processes, it is amphibolic (Figure 16—4). 

This enzyme is found in many tissues, where it catalyzes the reversible oxidative deamination of the amino acid glutamate. It produces the citric acid cycle intermediate a-ketoglutarate, which serves as an entry point to the cycle for a group of glucogenic amino adds. Its role in urea synthesis and nitrogen removal is stiU controversial, but has heen induded in Figure 1-17-1 and Table 1-17-1. 

Gluconeogenic precursors are molecules that can be used to produce a net synthesis of glucose. They include all the intermediates of glycolysis and the citric acid cycle. Glycerol, lactate, and the o-keto acids obtained form the deamination of glucogenic amino acids are the most important gluconeogenic precursors. 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

Some Aa are transaminated or deaminated to ketoacids, which are then metabolised by many pathways, including the Krebs-citric acid cycle (Figure 2.3). Others are metabolised to ammonia and urea by the Krebs-Fienseleit urea cycle (Figure 2.4). 

The carbon skeletons of several five-carbon amino acids enter the citric acid cycle at a -ketoglutarate. These amino acids are first converted into gluta-mate, which is then oxidatively deaminated by glutamate dehydrogenase to yield a-ketoglutarate (Figure 23.23). 

The carbon skeletons produced by these and other deamination reactions enter glycolysis or the citric acid cycle at many steps. For instance, we have seen that... 

Amino acids are oxidized in the mitochondria. The first step of amino acid catabolism is deamination, the removal of the amino group. The carbon skeletons of amino acids are converted into molecules that can enter the citric acid cycle. 

Aspartate, when it is deaminated, thus contributes directly to the insertion of additional molecules of oxaloacetate. Glutamate produces a-ketoglutarate, which, as a component of the citric acid cycle, is a precursor of oxaloacetate. 

Deamination of amino acids in animal tissue is generally effected by transamination with an a-keto-acid. In the majority of cases, this is 2-oxoglutarate formed by the citric acid cycle. Aspartate aminotransferase and alanine aminotransferase are examples of this kind of reaction. In Figure 2.7, transamination involving these enzymes is depicted as it is known to occur in mammalian liver. Note that the scheme shown here requires participation of oxalacetate and pyruvate and thus is intimately connected with metabolic pathways considered earlier. Serine and glycine are readily interconvertible in animal tissue by the enzyme serine hydroxymethyltransferase. It is worth noting also that decarboxylation of serine to ethanolamine as mentioned above can be followed by A -methylation to yield choline. Choline is both an essential component of many... 

Describe the reactions of transamination, oxidative deamination, and the entry of amino acid carbons into the citric acid cycle. 

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