Nitrogen, amino acid catabolism

General catabolic process Amino acid Nitrogen end product... 

Dehydrogenase Deficiency, Biotinidase Deficiency, and Adrenoleukodystrophy. Catabolism of essential amino acid skeletons is discussed in the chapters Phenylketonuria and HMG-CoA Lyase Deficiency. The chapters Inborn Errors of Urea Synthesis and Neonatal Hyperbilirubinemia discuss the detoxification and excretion of amino acid nitrogen and of heme. The chapter Gaucher Disease provides an illustration of the range of catabolic problems that result in lysosomal storage diseases. Several additional chapters deal with key aspects of intracellular transport of enzymes and metabolic intermediates the targeting of enzymes to lysosomes (I-Cell Disease), receptor-mediated endocytosis (Low-Density Lipoprotein Receptors and Familial Hypercholesterolemia) and the role of ABC transporters in export of cholesterol from the cell (Tangier disease). 

Reviews by Ruderman (19) and Adibi (20,21) indicate that the branched-chain amino acids, particularly leucine, have an important role along with alanine in gluconeogenesis. Leucine and the other two branched-chain amino acids are catabolized in skeletal muscle. The nitrogen that is removed from the branched-chain amino acids in skeletal muscle is combined with pyruvate and returned to the liver as alanine. In the liver the nitrogen is removed for urea production and the carbon chain is utilized as substrate for synthesis of glucose. Adibi et al. (22) reported that during the catabolic conditions of starvation, oxidation of leucine and fatty acids increases in skeletal muscles. While glucose oxidation is reduced, the capacity for oxidation of the fatty acid palmltate more than doubled, and leucine oxidation increased by a factor of six. 

The catabolism of proteins is much more complex than that of fats and carbohydrates because each of the 20 amino acids is degraded through its own unique pathway. The general idea, however, is that the amino nitrogen atom is removed and the substance that remains is converted into a compound that enters the citric acid cycle. 

The nitrogen source in the medium is the amino add glutamate. There are several cations K Mn2, Cn2, Zn2, Mg2, Co2, Fe2, Ca2 Mo6. Phosphate (POi") is the major anionic component. Fumaric add is a TCA cycle intermediate and may improve metabolic balance through the catabolic pathways and oxidation through the TCA cyde. Peptone may improve growth through the provision of growth factors (amino acids, vitamins, nudeotides). 

Figure 29-2. Overall flow of nitrogen in amino acid catabolism.

Removal of a-amino nitrogen by transamination (see Figure 28-3) is the first catabolic reaction of amino acids except in the case of proline, hydroxyproline, threonine, and lysine. The residual hydrocarbon skeleton is then degraded to amphibolic intermediates as outhned in Figure 30-1. 

In Saccharomyces cerevisiae, as in most eukaryotic cells, the plasma membrane is not freely permeable to nitrogenous compounds such as amino acids. Therefore, the first step in their utilization is their catalyzed transport across the plasma membrane. Most of the transported amino acids are accumulated inside the yeast cells against a concentration gradient. When amino acids are to be used as a general source of nitrogen, this concentration is crucial because most enzymes which catalyze the first step of catabolic pathways have a low affinity for their substrates. 

The regulation of NCR-sensitive amino acid transporters in Saccharomyces cerevisiae has many points in common with that of catabolic enzymes. Amino acid permeases, as well as some other transporters of nitrogenous nutrients, are integrated into the regulatory circuits, both general and specific, which control catabolic processes. 

The nitrogen contained in the amino acids is usually disposed of through the urea cycle. One of the early, if not the first, steps in amino acid catabolism involves a transamination using oxaloacetate or a-ketoglutarate as the amino-group acceptor. This converts the amino acid into a 2-keto acid, which can then be metabolized further. 

A protein that is unduT7 rich in the ten essential amino acids would not provide sufficient nitrogen for other metabolic processes without obligatory catabolism of the essential amino acids. Thus, the proportion of the total nitrogen intake that essential amino acids form indicate how a given protein fulfills nutritional requirements for proteins. This proportion, the E/T ratio (54), indicative of the amount of protein nitrogen supplied by essential amino acids, is (in g of essential amino acids per g of nitrogen)... 

The reaction shown in Figure 8.6 is also important in the liver where glutamate dehydrogenase is involved in the catabolism of amino acids and the entry of nitrogen into the urea cycle, as explained in Chapter 6. 

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