Biochemistry of Amino Acids - A. Mayer 1961

Disorders of amino acid metabolism in certain pathological conditions
Other disorders of amino acid metabolism

While a considerable number of aromatic amino acid metabolic anomalies have been described, relatively little is known about comparable disorders in the METABOLISM of fatty-series Amino Acids. Nevertheless, there is no reason to rule out the existence of inborn errors in aliphatic Amino acid metabolism. The accumulation of abnormal metabolic products may have gone unnoticed simply due to the difficulty of detecting such compounds. Aromatic derivatives, by contrast, are frequently easy to identify and isolate thanks to the distinctive properties of their aromatic groups.

Undoubtedly, many more amino acid metabolic anomalies remain to be discovered. Available data often do not permit definitive Conclusions. A number of abnormalities associated with The Development of neoplasms have been described and are discussed in detail by Greenstein [220]. Studies addressing the potential link between Cancer and Tryptophan Metabolism were cited earlier.

Significant interest has been sparked by recent findings regarding high concentrations of glutamine residue-containing Peptides in the Blood of certain patients suffering from celiac disease. It is hypothesized that in these patients, the Digestion of dietary gliadin breaks down largely only to peptides, which are then absorbed through the intestine. The Toxic Effect of wheat gluten gliadin on celiac patients appears to be associated with the appearance of these peptides [221, 222]. These studies clearly demonstrate that under certain conditions, fairly large amounts of peptides can be absorbed from the gut. The appearance of peptides in the blood following protein intake has long been documented [223]. Recently, the potential role of peptides in amino acid metabolism has once again attracted the attention of researchers [224] (p. 165).

The great diversity of Transamination reactions and their significance in metabolism have already been discussed in previous chapters. In 1955, it was established that glutamate-aspartate transaminase activity in blood serum is significantly elevated following myocardial infarction; this observation forms the basis for the clinical DIAGNOSTIC AND PROGNOSTIC application of transamination reactions [225—228]. In the blood serum of healthy individuals, the reaction rate between aspartic acid and α-ketoglutaric acid is extremely low. This reaction can be monitored by introducing malate dehydrogenase and reduced diphosphopyridine nucleotide into the reaction system and observing the decrease in optical density at 340 mµ resulting from coenzyme oxidation. Within one to two days after the onset of clinical signs of myocardial infarction, serum transaminase activity is elevated 2- to 10-fold compared to normal levels. Transaminase activity returns to normal within approximately 5 days, provided the lesion does not extend to new areas of the myocardium. In a series of experiments involving experimentally induced myocardial infarction in dogs, the level of enzyme activity in the blood serum was proportional to the size of the infarcted Heart Muscle area [227]. Given the widespread distribution of glutamate-aspartate transaminase, an increase in serum activity of this transaminase might also be expected upon damage to other Organs. Such elevations have indeed been observed in Liver diseases and other pathological conditions. Nevertheless, the determination of serum transaminase activity, when correlated with other clinical findings, is of clear practical interest. It appears that in myocardial infarction, other enzyme systems (such as Lactate dehydrogenase) also pass from The Heart muscle into Blood Plasma [229].

Histamine is widely distributed in animal Tissues and undoubtedly plays a major physiological role (see reviews by Rose [230], Code [231], and Tabor [232]).

It is now well established that relatively large amounts of histamine are concentrated in mast Cells, which also contain heparin. A recently published report describes generalized mast Cell hyperplasia in a patient suffering from urticaria pigmentosa [233]. The concentration of histamine in The Liver and Spleen of this patient was exceptionally high—approximately 100 times the normal level of 10—12 µg per gram of tissue—while liver Histidine decarboxylase activity was also several hundred times above normal. Evidently, this condition is associated with a congenital hyperactivity of histidine decarboxylase; whether this defect represents a primary "inborn error of metabolism" or a secondary phenomenon remains to be determined.