Pathways of Amino Acid Degradation:- Seven Amino Acids Are Degraded to Acetyl-CoA
Portions of the carbon skeletons of seven amino acids— tryptophan, lysine, phenylalanine, tyrosine, leucine, isoleucine, and threonine—yield acetyl-CoA and/or acetoacetyl-CoA, the latter being converted to acetyl CoA (Fig. 18–21). Some of the final steps in the degradative pathways for leucine, lysine, and tryptophan re semble steps in the oxidation of fatty acids. Threonine (not shown in Fig. 18–21) yields some acetyl-CoA via the minor pathway illustrated in Figure 18–19. The degradative pathways of two of these seven amino acids deserve special mention. Tryptophan break down is the most complex of all the pathways of amino acid catabolism in animal tissues; portions of tryptophan (four of its carbons) yield acetyl-CoA via acetoacetyl CoA. Some of the intermediates in tryptophan catabolism are precursors for the synthesis of other biomolecules (Fig. 18–22), including nicotinate, a precursor of NAD and NADP in animals; serotonin, a neurotransmitter in vertebrates; and indoleacetate, a growth factor in plants. Some of these biosynthetic pathways. The breakdown of phenylalanine is noteworthy because genetic defects in the enzymes of this pathway lead to several inheritable human diseases (Fig. 18–23), as discussed below. Phenylalanine and its oxidation product tyrosine (both with nine carbons) are degraded into two fragments, both of which can enter the citric acid cycle: four of the nine carbon atoms yield free ace to acetate, which is converted to acetoacetyl-CoA and thus acetyl-CoA, and a second four-carbon fragment is recovered as fumarate. Eight of the nine carbons of these two amino acids thus enter the citric acid cycle; the remaining carbon is lost as CO2. Phenylalanine, after its hydroxylation to tyrosine, is also the precursor of dopamine, a neurotransmitter, and of norepinephrine and epinephrine, hormones secreted by the adrenal medulla. Melanin, the black pigment of skin and hair, is also derived from tyrosine.
FIGURE 18–21 Catabolic pathways for tryptophan, lysine, phenyl alanine, tyrosine, leucine, and isoleucine. These amino acids donate some of their carbons (red) to acetyl-CoA. Tryptophan, phenylalanine, tyrosine, and isoleucine also contribute carbons (blue) to pyruvate or citric acid cycle intermediates. The phenylalanine pathway is described in more detail in Figure 18–23. The fate of nitrogen atoms is not traced in this scheme; in most cases they are transferred to ketoglutarate to form glutamate.
acid catabolism in animal tissues; portions of tryptophan (four of its carbons) yield acetyl-CoA via acetoacetyl CoA. Some of the intermediates in tryptophan catabolism are precursors for the synthesis of other biomolecules (Fig. 18–22), including nicotinate, a precursor of NAD and NADP in animals; serotonin, a neurotransmitter in vertebrates; and indoleacetate, a growth factor in plants. Some of these biosynthetic pathways are described in more detail. The breakdown of phenylalanine is noteworthy because genetic defects in the enzymes of this pathway lead to several inheritable human diseases (Fig. 18–23), as discussed below. Phenylalanine and its oxidation product tyrosine (both with nine carbons) are degraded into two fragments, both of which can enter the citric acid cycle: four of the nine carbon atoms yield free acetoacetate, which is converted to acetoacetyl-CoA and thus acetyl-CoA, and a second four-carbon fragment is recovered as fumarate. Eight of the nine carbons of these two amino acids thus enter the citric acid cycle; the remaining carbon is lost as CO2. Phenylalanine, after its hydroxylation to tyrosine, is also the precursor of dopamine, a neurotransmitter, and of norepinephrine and epinephrine, hormones secreted by the adrenal medulla (see Fig. 22–29). Melanin, the black pigment of skin and hair, is also derived from tyrosine.
FIGURE 18–22 Tryptophan as precursor. The aromatic rings of tryptophan give rise to nicotinate, indoleacetate, and serotonin. Colored atoms trace the source of the ring atoms in nicotinate.
