Abnormal Protein Metabolism Research Articles

Abnormal amino acid and protein metabolism in uremia

The many alterations in amino acid and protein metabolism in renal failure are often poorly defined, and the available data concerning them are usually descriptive. Nonetheless, certain factors play an important role in the altered amino acid and protein metabolism of uremia. These include malnutrition caused by poor nutrient intake, loss of nutrients during dialysis, and abnormal metabolism of nutrients. Other factors include uremic toxins, superimposed catabolic illnesses, endocrine disorders, and the reduced capacity of the failing kidney to synthesize or degrade certain hormones, amino acids, peptides, and small proteins. These aberrations have complex interrelationships which sometimes potentiate each other. It is possible that the administration of sufficient quantities of energy, vitamins, and minerals, as well as the dietary manipulation of protein, amino acid and ketoacid intake may improve the metabolism of amino acids and proteins. Vitamin B6 and zinc have special requirements that may affect protein or amino acid metabolism.

NUTRITIONAL ASPECTS OF MILK PROTEIN

The significance of milk proteins in human nutrition is discussed in the light of the considerable advances in the understanding of their chemistry which have been made recently. In particular comparison is made of the effectiveness of milk proteins and those from other sources in fulfilling human requirements for essential amino acids and attention is drawn to the possible significance of the predominantly phospho‐protein character of milk proteins. Finally consideration is given to the use of milk proteins as the basic raw material for specialist preparations designed to meet nutritional requirements in circumstances of abnormal protein metabolism and to possible ill effects to be expected from ingestion of milk protein.

PHENYLKETONURIA AND THE PHENYLALANINEMIAS OF INFANCY

In 1965 this Committee issued a statement outlining the responsibilities of the physician to the child with phenylketonuria, an inherited abnormality of amino acid metabolism. A lack of knowledge about the disorder and about the results of treatment placed constraints on the 1965 statement. The Committee therefore feels that, with recent advances in knowledge about the disorder, a new statement is needed. An increased level of phenylalanine in the blood can occur under sporadic and transient conditions in the absence of disease, with or without a concomitant elevation of serum tyrosine; it is always present in the disorder now called phenylketonuria. Because of incomplete information, simple classification of a specific case of phenylalaninemia is often not possible. Screening programs allow for the detection of infants with elevated blood levels of phenylalanine. Screening programs should be encouraged and supported because they are the best available means for identifying all infants with abnormalities of protein metabolism resulting in serum phenylalanine elevations. Two important, unresolved issues need clarification: (1) the effect of a persistently elevated blood level of phenylalanine on the intellectual growth of the child when there are no other indications of disease, and (2) the possibility of harmful effects of a diet low in phenylalanine. The basic treatment of phenylketonuria is to reduce circulating phenylalanine by dietary restriction; and, because a spectrum of disorders causes an elevation of that amino acid, differing approaches in management seem indicated. The relative rarity of phenylketonuria precludes the opportunity for individual physicians to gain widespread experience and expertise in management outside of a hospital specialty clinic setting.

Evaluation of amino acid and protein requirements in chronic uremia

Plasma amino acids were found to deviate extensively from normal in patients with end-stage uremia. Concentrations of all essential amino acids except phenylalanine and methionine were reduced. Progressive impairment of reabsorption of amino acids by the kidney is found as glomerular filtration rate (GFR) falls, renal clearances increasing fivefold to fortyfold at GFR less than 10 ml/min. Impairment of absorption of amino acids by the small intestine may explain the abnormal plasma curves after oral loading with tryptophan. These and other abnormalities may be the basis for development of abnormal protein metabolism in chronic, progressive renal failure in man.

Divergent responses of arteriosclerotic and non-arteriosclerotic rats to a catabolic dose of cortisone.

ABSTRACT Male and female rats bred repeatedly develop arteriosclerosis spontaneously. Current information indicates that stimulation of the hypothalamic-pituitary-adrenal axis in association with the active, repeated breeding may be responsible for the increased adrenocortical steroid production which would account for the abnormal lipid, carbohydrate and protein metabolism and arteriosclerosis observed in these animals. Arteriosclerotic breeder rats and non-arteriosclerotic virgin rats were given chronic injections of cortisone. The arteriosclerotic animals showed the most significant catabolic effects due to overdose with steroid, i. e., loss in body weight, disuse atrophy of the adrenal gland, reduced serum corticosterone levels, thymus gland involution, myocardial and renal changes. The excess glucocorticoid caused an acceleration of the usual pattern of development of the arterial disease and increased severity of the pre-existing arteriosclerosis. The excess endogenous steroid did not induce arterial damage in previously non-arteriosclerotic animals. It is believed that the increased activity of the hypothalamic-pituitary-adrenal axis in repeatedly bred rats conditions the arterial wall towards derangement of connective tissue ground substance and elements and the development of arteriosclerosis, i. e., a hormonal basis for the pathogenesis of this model of cardiovascular disease.

Pipecolic acid as an indicator of abnormal protein metabolism in diseased plants

During the study of the free amino acid spectrum of diseased rice, soybean, potato and tobacco leaves, an unknown compound was detected, the occurrence of which was correlated with an abnormal physiological condition of the plants or with some disturbance in amino acid or protein metabolism. On chromatograms this substance stains blue following fixation with cupric nitrate. After purification with the aid of bacteria, this ‘blue substance’ was identified as pipecolic acid.

ABNORMAL INCREASE OF AMIDE NITROGEN IN CYTOPLASMIC MALE-STERILE WHEAT

The protein content of sterile anthers and vegetative parts of cytoplasmic malesterile wheat plants was estimated by the measurement of the nitrogen in alcohol-precipitable and -soluble fractions. Sterile anthers showed a remarkable decrease of nitrogen in the alcohol-precipitable fraction, as compared with normal fertile anthers. In contrast, a remarkable increase of nitrogen content especially of amide nitrogen occurred in the alcohol-soluble fraction. Similar abnormal conditions were observed in germinating embryos and young seedlings.It is suggested that abnormal protein metabolism might occur initially at germination and continue during the growth of the plant, with a resulting retardation of growth, reduction of plant height and finally pollen degeneration.

Blood proteins in functional psychoses. A review of the literature and unifying hypothesis.

The question of abnormal blood proteins of various sorts in the functional psychoses has been rather extensively investigated. The work is scattered throughout the world literature and much of it is in Russian. The purpose of this paper is to bring together some of the important work of the last 10 years. Most of the literature reviewed is in English. Some of the Russian and Continental work has been covered, but the unavailability of some relevant papers and the difficulties of translation have limited the review of foreign work. Several theories about the role of abnormal protein metabolism in the etiology or pathogenesis of the functional psychoses have recently been proposed. Some 53-59 have suggested that a circulating protein, taraxein, produces the schizophrenic reaction. I 30-34 and others 123 have speculated that the psychotic reaction in some cases may result from an autoimmune reaction directed against

Alterations of protein metabolism in myxedema

W I’IYH the exception of the reduction in total energy exchange, perhaps the most conspicuous alteration in the athyrotic state is that in protein metabolism.“’ This statement by Means clearly poses the problem which is the subject of this presentation. Protein abnormalities in myxedematous patients have interested investigators for some time, and it is the purpose of this communication to summarize some of these studies. An attempt will be made to correlate studies from our laboratory with those in the literature in an effort to formulate a working concept of abnormalities of protein metabolism in patients with myxedema. Experimental investigations in animals which apply to this problem will also be reviewed.

Multiple myeloma

1. Multiple myeloma is an uncommon but uniquely important disease, and it is encountered with increasing frequency. 2. Clinically, the occurrence of pain, especially in the back, unexplained anemia or proteinuria in older people should arouse suspicion of multiple myeloma. The diagnostic importance of bone changes by x-ray, of marrow aspiration and of use of paper electrophoresis of the serum and urine has been stressed. 3. The treatment of myeloma, in common with that of most neoplastic disorders, is unsatisfactory. However, some patients obtain remissions on urethan, and painful bone lesions are greatly improved by local x-ray therapy. 4. The abnormal protein metabolism in myeloma is a fascinating aspect of this disease and presents fundamental problems concerning the synthesis of globulins in plasma cell dyscrasias. The role of these proteins in the pathogenesis of renal damage and para-amyloidosis has been discussed in the light of newly acquired immunologic and physicochemical knowledge.

Multiple myeloma: report of a case showing unusual remission lasting two years following severe hepatitis.

Excerpt In the past 25 years multiple myeloma has been regarded with interest because of the increasing number of reported cases,1, 2, 3, 4the curious associated abnormalities in protein metabolism...

Plasmacytoma of the mandible

Plasmacytoma of the mandible

PHILADELPHIA PSYCHIATRIC SOCIETY

as compared with their results in other, reputedly normal persons. They base their opinion also on the fact that malononitrile was known previously to change the protein contents of the nerve cell and will change the nucleoprotein metabolism in experimental rabbits. The results of these experiments have now been applied in extended and repeated investigations and have given further valuable data. However, the question comes to mind of how well founded is the assumption of abnormal protein metabolism in connection with mental disorders. I agree with Dr. Meyers and his co-workers that further large scale investigations are necessary. They confess that their evidence is based on four known cases, which cannot be regarded as sufficient, as they also point out. I shall not discuss the biochemistry, however interesting. I have in mind a question on which I should like to have Dr. Meyers' opinion. It is known that insulin also increases the protein content of nerve cells. Malononitrile is more agreeable to the patient than insulin. Malononitrile undoubtedly increases the protein content of the nerve cell ; insulin does this also. I wonder whether there is a link, and whether Dr. Meyers thinks his experience with malononitrile actually supports the idea of replacing insulin in certain cases with malononitrile. Dr. Dixon Meyers : With regard to the question of malononitrile replacing insulin, at present I do not think one could say that it should. It is true that in some of these cases malononitrile did as much as has insulin in the past, but the drug is still too new to be considered a substitute.

THE TREATMENT OF DELIRIUM TREMENS WITH INSULIN IN SUB-SHOCK DOSES

Insulin with carbohydrates seems at this time to be the only method of treating delirium tremens which has improved upon the statistical results reported by Kraepelin, who used diet, support and paraldehyde for rest. Insulin is effective because it rapidly re-establishes normal carbohydrate metabolism. It likewise quickly replaces deficient glycogen reserves in the liver. These two factors, which are part of the same process, re-vitalize the liver and re-establish normal protein and fat metabolism. During the period of deficient carbohydrate metabolism and deficient liver function, toxic intermediate products of abnormal protein and fat metabolism have become so concentrated that they have produced the pathology and symptoms of delirium tremens. Re-establishment of the liver function advances the progress of metabolism, and these products are carried forward to their ultimate normal, less noxious end products. This reduces toxic concentrations, removes the "irritative" factor, the cerebral pathology reverses itself by natural processes, and the delirium is quickly relieved. Insulin therapy is rapid, effective and simple to administer. The series presented by Steck and by me had a combined time for complete clearing of the delirium of 2.5 days.