Transamination Typically Initiates 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 outlined in Figure 30-1.

Asparagine, Aspartate, Glutamine, and Glutamate. All four carbons of asparagine and aspartate form oxaloacetate (Figure 30-2, top). Analogous reactions convert glutamine and glutamate to a-ketoglu-tarate (Figure 30-2, bottom). Since the enzymes also fulfill anabolic functions, no metabolic defects are associated with the catabolism of these four amino acids.

Proline. Proline forms dehydroproline, glutamate-Y-semialdehyde, glutamate, and, ultimately, a-ketoglu-tarate (Figure 30-3, top). The metabolic block in type I hyperprolinemia is at proline dehydrogenase.

Figure 30-1. Amphibolic intermediates formed from the carbon skeletons of amino acids.

Figure 30-1. Amphibolic intermediates formed from the carbon skeletons of amino acids.

I NH2 ch2

ASPARAGINASE

TRANSAMINASE

CH2 V I

ch2 I

GLUTAMINASE

ch2 I

TRANSAMINASE

ch2 I

C°°-a-Ketoglutarate

Figure 30-2. Catabolism of L-as-paragine (top) and of L-glutamine (bottom) to amphibolic intermediates. (PYR, pyruvate; ALA, L-alanine.) In this and subsequent figures, color highlights portions of the molecules undergoing chemical change.

There is no associated impairment of hydroxyproline catabolism. The metabolic block in type II hyperpro-linemia is at glutamate-^-semialdehyde dehydrogenase, which also functions in hydroxyproline catabolism. Both proline and hydroxyproline catabolism thus are affected and A!-pyrroline-3-hydroxy-5-carboxylate (see Figure 30-10) is excreted.

Arginine and Ornithine. Arginine is converted to ornithine, glutamate y-semialdehyde, and then a-ke-toglutarate (Figure 30-3, bottom). Mutations in ornithine 8-aminotransferase elevate plasma and urinary ornithine and cause gyrate atrophy of the retina. Treatment involves restricting dietary arginine. In hy-perornithinemia-hyperammonemia syndrome, a defective mitochondrial ornithine-citrulline antiporter (see Figure 29-9) impairs transport of ornithine into mitochondria for use in urea synthesis.

Histidine. Catabolism of histidine proceeds via urocanate, 4-imidazolone-5-propionate, and N-for-miminoglutamate (Figlu). Formimino group transfer to tetrahydrofolate forms glutamate, then a-ketoglu-tarate (Figure 30-4). In folic acid deficiency, group transfer is impaired and Figlu is excreted. Excretion of Figlu following a dose of histidine thus has been used to detect folic acid deficiency. Benign disorders of histi-dine catabolism include histidinemia and urocanic aciduria associated with impaired histidase.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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