Disturbance Of Amino Acid Metabolism Research Articles

Acute intermittent porphyria and disturbances in amino-acid metabolism in a psychiatric in-patient population

SummaryIn recent years an enhanced catabolism of serine, with or without the existence of porphyria, has been demonstrated in relation to a specific subtype of psychosis, according to ICD-10 criteria, the acute polymorphic psychosis with or without symptoms of schizophrenia. Since sensory perceptual distortions play a key role in the symptomatology, patients with this disorder are referred to as Acute Polymorphic Psychosis plus psychosensory phenomena (APP+). In a retrospective study, including a total of 140 chronic psychiatric patients, we investigated the prevalence of Acute Intermittent Porphyria (AIP) and APP+. No subjects with AIP were found. In two patients APP+ could be demonstrated, based on both clinical characteristics and positive biochemical markers, ie lowered plasma serine concentration and increased TSM-ratio (100 × Taurine (μmol/l)/Serine concentration * Methionine concentration). In three patients the psychotic disorder was suspected to be present. It is concluded that careful psychiatric diagnosing may reveal specific psychotic disorders with a distinct biological pathogenetic factor, ie a disturbed serine metabolism.

Decreased plasma proteins, increased total plasma-free amino acids, and disturbed amino acid metabolism in the hereditary severe anemia of the Belgrade laboratory (b/b) rat.

The plasma amino acid pattern has been investigated in severely anemic Belgrade laboratory (b/b) rats. Nonanemic heterozygous (b/+) or normal homozygous (+/+) rats of the same age (six weeks) were used as controls. Decreased plasma proteins, increased total free amino acid, and urea concentrations in plasma associated with increased urea and 3-methylhistidine urinary excretion were found, indicating protein and amino acid metabolic alterations in anemic b/b rats. Plasma alanine, glutamine, tyrosine, and phenylalanine concentrations were increased. The significantly reduced molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine suggested severe disturbance in the hepatic energy-producing system and derangement of hepatic energy status. Partial or complete reversal of the anemia within 3 days by red blood cell transfusion or within 3 weeks by iron treatment resulted in normalization of tyrosine, alanine, glutamine, and total amino acid concentrations in plasma, as well as of molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine. This indicated a better oxygen supply to the liver and normalization of the hepatic energy status. These findings suggest that the metabolic disturbances in the b/b rat are the consequence of hypoxia due to the severe anemia.

Effects of Insulin on Free Amino Acids in Plasma and the Role of the Amino Acid Metabolism in the Etiology of Diabetic Microangiopathy

To investigate if alterations of the amino acid metabolism may play a more important role in the etiology of diabetic microangiopathy than hitherto recognized, free amino acids in plasma were measured by means of high-performance liquid chromatography (HPLC) in healthy individuals (REF) and patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Isoleucine and leucine in IDDM were within normal limits, whereas they were significantly higher in NIDDM (P < 0.01 and P < 0.001, respectively). This was not due to age differences. In order to evaluate the impact of insulin on amino acid metabolism, amino acids were also measured in pregnant women (PREG) undergoing glucose tolerance tests as a screening for pregnancy diabetes and in patients with polycystic ovary syndrome (PCO) undergoing euglycemic insulin clamp tests. Insulin considerably reduced the amino acid concentration. Isoleucine and leucine were particularly depressed. On the whole there was strong covariance between the three branched-chain amino acids, isoleucine, leucine, and valine (P < 0.0001). There was no covariance between amino acid and glucose or HbA1c concentrations. A protein meal strongly stimulated insulin production (+55 mIU/liter), whereas a galactose meal revealed only a minor increase in insulin response (+12 mIU/liter) in contrast to a tolerance test with the same amount of glucose (+67 mIU/liter). It is concluded that disturbed amino acid metabolism may be a more important causative factor in the etiology of diabetic microangiopathy than hitherto recognized and, in addition, that this may affect the therapeutic approach in both IDDM and NIDDM patients.

Brain amino acid reductions in one family with chromosome 6p—linked dominantly inherited olivopontocerebellar atrophy

We measured the levels of aspartate, glutamate, gamma-aminobutyric acid (GABA), and other amino acids in autopsied brain of 6 patients from one family (Pedigree S) with dominantly inherited olivopontocerebellar atrophy. A previous demonstration of reduced aspartate concentration in plasma of affected members of this family suggested the possibility of a generalized disorder of amino acid metabolism affecting the brain. As compared with the control levels, mean levels of aspartate and glutamate were markedly reduced by about 70 and 40%, respectively, in the degenerated cerebellar cortex from the patients. Since the cerebellar aspartate reduction likely exceeds the amount that could be explained by neuronal loss, other factors such as abnormal aspartate metabolism, neurotransmitter turnover, or both are probably involved. Mean aspartate, glutamate, and GABA levels were also reduced by about 10 to 30% in most of the 16 examined extracerebellar brain areas in which no or, at most, mild neuronal cell loss was observed by semiquantitative estimation. Concentrations of taurine, glutamine, and omicron-phosphoethanolamine were normal in all brain areas examined. Our biochemical data provide support to the presence of a generalized, but quantitatively mild, disturbance in amino acid metabolism in patients with olivopontocerebellar atrophy from Pedigree S. The regionally widespread amino acid reductions in the brain, of as yet unknown pathophysiological significance, could be due to a failure of one or more enzymes involved in aspartate and glutamate metabolism.

Katabolismus und künstliche Ernährung des internistischen Intensivpatienten

Numerous investigations have been performed on catabolism in polytrauma and surgery. Comparable studies on the internal medical intensive-care patient are not available. Such patients have an increasing metabolism with a maximum attained on day 5, and the catabolic condition is associated with an increased muscle protein breakdown. Objective measurements of catabolism and nutritional status are important but difficult. The recovery of a patient after acute illness depends on the provision of sufficient and adequate nutrition in three steps: 1. quantity and quality of calories; 2. quantity and quality of protein; 3. vitamins and electrolytes. Glucose is one source of calories as are fructose, xylit, and fat. Quantity and quality of amino acids are relative to organ failure and disturbance of amino acid metabolism. Branched-chain amino acids may be helpful in hepatic failure and severe sepsis.

Hypogonadism in liver cirrhosis: Implication in altered amino acid metabolism in muscle

To investigate the relationship between hypogonadism and altered amino acid metabolism in patients with liver cirrhosis, we measured the basal levels of plasma testosterone, estradiol, and free amino acids, plus urinary 3-methylhistidine excretion, in 16 control and 19 cirrhotic patients. The concentration of plasma testosterone correlated significantly with that of plasma branched-chain amino acids, and inversely with urinary 3-methylhistidine excretion. This suggests that hypogonadism causes a disturbance in amino acid metabolism at least partly related to an augmented muscle protein turnover.

Nutrition and alcoholic encephalopathies

An assessment has been made of metabolic factors possibly causing or contributing to the brain damage associated with chronic alcoholism, especially thiamin lack or disturbance of amino acid metabolism. Abnormalities in the thiamin-dependent enzyme, transketolase, provide evidence of a high incidence of thiamin deficiency as well as of disturbed thiamin metabolism in chronic alcoholics, which are likely to be caused by reduced vitamin intake as well as impaired absorption. A grossly disturbed pattern of amino acids in the blood of patients undergoing treatment for alcohol withdrawal syndromes is likely to be caused by loss of hepatic function and may well aggravate brain damage caused by B group vitamin deficiency. A hypothesis is proposed of how chronic thiamin lack can lead to brain damage.

Canine Cystine Urolithiasis

Cystine uroliths form as a result of a complex metabolic disturbance in amino acid metabolism and transport. The inheritance of this disease is obscure because it does not follow a standard mendelian pattern. Uroliths are a vexing clinical problem because the recurrence rate is high. Accurate diagnosis of uroliths requires use of crystallographic methods. The renal defect leading to excessive excretion of cystine is variable. The only effective method of prevention of recurrence is use of D-penicillamine, which is poorly tolerated by some dogs.

The effect of perinatal anoxia on amino acid metabolism in the developing brain. Part II: The effect of perinatal anoxia on the free amino acid patterns in CSF of infants and children

To clarify the effects of perinatal anoxia on the subsequent amino acid metabolism in the brain of children, free amino acid levels in the cerebrospinal fluid (CSF) were determined in 15 children diagnosed as having cerebral palsy and/or mental retardation with perinatal anoxia, and 58 control children without anoxia, aged from 4 days to 12 yrs. There was no significant difference in total amino acid levels between anoxic children and the controls. In the controls, the Gln level in CSF was high, Arg, Asp and Glu levels in CSF were almost the same during infancy and childhood, and the levels of Orn, Lys, His, Tau, Thr, Ser, Asn, Gly, Ala, Val, Met, Ile, Leu, Tyr and Phe in CSF decreased with age until pre-school age. In the newborns and infants among the anoxic children, the levels of most free amino acids in CSF were relatively high compared with those of the controls and, except Glu and Gln, decreased with age during infancy. The Orn, His, Gly, Tyr and Phe levels in CSF of anoxic children were lower than those of the controls in older infants. These results suggest that perinatal anoxia affected free amino acid patterns in CSF of newborns and infants and that the subsequent disturbance of amino acid metabolism in their brains remained after birth.

BOOK REVIEWS

Book reviewed in this article:H. Olbing: Rezidivierende nicht‐obstruktive Harnwegsin‐fektionen bei Kindern.H. J. Bremer, M. Duran, J. P. Kamerling, H. Przyrembel &amp; S. K. Wadman: Disturbances of amino acid metabolism: Clinical chemistry and diagnosis.J. O. Haller &amp; M. Schneider: Pediatric ultrasound.F. Falkner: Prevention in childhood of health problems in adult life.Vernon Smith &amp; John Keen: Visual handicap in children.

Induction of Fatty Liver and Disturbance of Amino Acid Metabolism in Vitamin B_6-Deficient Rat

Induction of Fatty Liver and Disturbance of Amino Acid Metabolism in Vitamin B_6-Deficient Rat

The acute effect of ethanol on albumin, fibrinogen and transferrin synthesis in the rat.

Decrease of absolute synthesis of albumin and fractional synthesis of transferrin was observed within 3h of orally administering ethanol (4ml/kg) to rats maintained on a 40%-protein diet. In contrast, absolute synthesis of fibrinogen was unaffected. With this ethanol intake, the changes in protein synthesis occurred without significant ultrastructural change in the liver. When the ethanol intake was greater (8ml/kg) ultrastructural disruption was observed. However, both the decrease of plasma protein synthesis and the ultrastructural alterations could be prevented by the simultaneous administration of a mixture of amino acids with the ethanol. The latter findings, not reported hitherto, suggest that ethanol may interfere with hepatic plasma protein synthesis and ultrastructure more through a disturbance of amino acid metabolism than through direct physical damage to the hepatocyte. An Appendix outlines the deconvolutional method used to correct for losses of labelled protein in the period during which measurements were made. The principle may also be applied to labelled plasma urea. The details of the calculations are given in a supplementary paper that has been deposited as Supplementary Publication 50007 at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1972) 126, 5.

Disturbance of Amino Acid Metabolism Induced by Ro 4-4602, A Peripheral Decarboxylase Inhibitor

Disturbance of Amino Acid Metabolism Induced by Ro 4-4602, A Peripheral Decarboxylase Inhibitor

Free amino acids and proteins in plasma of pregnant patients with megaloblastic anaemia.

Summary.Plasma proteins and free amino acids were estimated in 18 non‐anaemic pregnant and 16 severely anaemic pregnant or recently delivered Nigerians. The mean concentration of all plasma free amino acids, except arginine, was raised in 15 women with megaloblastic anaemia secondary to folate deficiency. Some amino acid levels in individual patients were over 5 times the highest concentration recorded in the non‐anaemic. All plasma free amino acids were within the normal range in one patient with iron deficiency anaemia and heavy hookworm infestation. The mean albumin, α2 globulin and total protein concentrations were slightly but significantly lower in the anaemic patients.These findings have been discussed in support of a hypothesis that folate‐ or vitamin B12‐deficiency leads to a failure of methylation and formylation of tRNA and rRNA, so that coding is interrupted and cells are unable to form mature ribosomes. This results in an accumulation of free amino acids in cellular and extracellular pools with overflow amino aciduria. Haemoglobinopathies, haemolysis, malaria and liver failure were unlikely to have been causes of the high plasma amino acid concentrations observed in these women.It is probable that this disturbance of amino acid metabolism affects adversely uterine hypertrophy, placental development and foetal growth.

Les Maladies Métaboliques Des Acides Aminés Avec Arriération Mentale.

This newest volume devoted to disturbances of the amino acids represents a collaborative effort by four French authors. The book itself is divided into five sections: (1) general metabolic pathways of amino acids; (2) biochemical methods used for investigating amino acid disturbances; (3) pathological syndromes resulting from disturbances of amino acid metabolism; (4) their diagnosis based upon clinical symptoms; and (5) their diagnosis based upon laboratory tests. There is an appendix giving biochemical procedures used in the detection of amino acid disturbances. The book is clearly written and the references are up to date. The figures and tables are useful in explaining the text. The authors obviously have a broad understanding on the worldwide controversies on certain specific problems, and those they present in a logical and unbiased manner. The volume is also quite complete in that all of the known amino acid disturbances are discussed in detail. This reference

Tissue protein breakdown in burns

A study was made of the autolytic activity of tissues and transaminase activity of rabbit serum with experimentally induced burns. As established, on the 2nd day after the burn there was a considerable rise in the activity of glutamico-oxaloacetic and glutamico-puropyruvic transaminases with a subsequent normalization of these indices. The autolytic activity of the tissues studied remained within the normal range on the 2nd day. Four days after the burn and during the subsequent periods the autolytic activity is considerably, intensified in the skeletal muscle and in the liver at the expense of the enzymes acting in the acid medium. Oxygen absorption by the body rose directly after the experiment, normalized on the 2nd day and increased (+35%) during the 2nd and 3rd weeks of the disease. A rise of transaminase activity is considered to be the sequence of direct disturbance of amino acid metabolism, whereas autolysis intensification—the reflection of increased disintegration of intact tissues.

Ocular manifestations of systemic cystinosis.

Cystinosis, or the Lignac-Fanconi syndrome, is a disease of childhood that is characterized by dwarfism and by the accumulation of cystine crystals within many tissues of the body. Investigation reveals a generalized aminoaciduria and renal tubular dysfunction, which is usually manifest by acidosis, hypokalemia, and impaired water reabsorption. Renal rickets and uremia are frequent late sequelae. While the disturbance is believed to be a hereditary defect in the utilization of many amino acids, cystine precipitates out, presumably because of its low solubility. The condition is not to be confused with the relatively benign cystinuria which appears to result from a lowered renal threshold (for cystine, lysine, and arginine) and which does not reflect a general disturbance of amino acid metabolism, such as is the case with the cystinosis of children. The ophthalmologic importance of cystinosis is due to the fact that the crystals of cystine can be frequently seen in