Human Biochemistry, Volume 1 - Murray R. 1993

Metabolism of Proteins and Amino Acids
Catabolism of the Carbon Skeleton of Amino Acids
Biomedical Significance

Historically, certain human Amino acid METABOLISM disorders played a pivotal role in elucidating amino acid Metabolic Pathways in healthy individuals. Many of these conditions are rare, and consequently, most practicing physicians rarely encounter them. Nevertheless, these disorders are of profound interest to psychiatrists, pediatricians, genetic counselors, and biochemists. They most frequently manifest in childhood and often prove fatal at an early age; if left untreated, they can cause irreversible Brain damage. It is crucial that the disease is diagnosed as early as possible and appropriate Treatment initiated immediately, where feasible. Because The activity of several Enzymes related to these Metabolic Disorders can be assayed in Amniotic Fluid Cell cultures, prenatal Diagnosis is possible via amniocentesis. Current treatment typically involves dietary restriction of the Amino Acids whose Catabolism is impaired; however, more effective therapies are on the horizon. For instance, a patient's Blood could be passed through a Column containing the deficient enzyme in an immobilized state, thereby compensating for the enzyme's absence or insufficient activity within the body. Looking to the future, Recombinant DNA technology may enable the Correction of Genetic defects ("Gene Therapy").

The metabolic disorders in question stem from genetic Mutations that lead to the synthesis of Proteins with altered primary structures. Depending on The Nature of these Primary Structure modifications, structural changes may also occur at other levels. While some alterations in the primary structure have no significant effect on enzyme activity, others can profoundly impact the three-dimensional STRUCTURE OF THE catalytic or regulatory site (see Chapters 6 and 7). A modified (mutant) enzyme may exhibit altered catalytic efficiency (a low V_max or a high K_m) or a diminished capacity to bind Allosteric regulators of catalytic activity. In principle, different mutations can produce identical clinical manifestations. For example, any mutation that results in a substantial decrease in argininosuccinase catalytic activity (see Fig. 30.13) will cause the metabolic disorder known as argininosuccinic aciduria. However, it is unlikely that all cases of argininosuccinic aciduria are caused by the exact same alteration in the Introduction/19.html">Primary structure of argininosuccinase. In this sense, such cases represent distinct molecular diseases. This chapter examines several well-known disorders of amino acid metabolism. Readers seeking further Examples can consult specialized textbooks (e.g., Stanbury et al., 1983).

We will begin by tracing the pathways for The conversion of the carbon skeletons of L-amino acids into amphibolic intermediates. Next, we will examine the characteristic human disorders associated with these Catabolic pathways.