Brain amino acid metabolism

Brain Coordination of the nervous system Glycolysis, amino acid metabolism Glucose, amino acid, ketone bodies (in starvation) Polyunsaturated fatty acids in neonate Lactate ... 

In earlier studies the in vitro transition metal-catalyzed oxidation of proteins and the interaction of proteins with free radicals have been studied. In 1983, Levine [1] showed that the oxidative inactivation of enzymes and the oxidative modification of proteins resulted in the formation of protein carbonyl derivatives. These derivatives easily react with dinitrophenyl-hydrazine (DNPH) to form protein hydrazones, which were used for the detection of protein carbonyl content. Using this method and spin-trapping with PBN, it has been demonstrated [2,3] that protein oxidation and inactivation of glutamine synthetase (a key enzyme in the regulation of amino acid metabolism and the brain L-glutamate and y-aminobutyric acid levels) were sharply enhanced during ischemia- and reperfusion-induced injury in gerbil brain. 

Imbalances of brain amino acids may hinder the synthesis of brain lipids, leading to a diminution in the rate of myelin formation. Decreases of lipids, proteolipids and cerebrosides (Ch. 3) have been noted in several of these syndromes, e.g. maple syrup urine disease, when intra-myelinic edema is a prominent finding, particularly during the acute phase of metabolic decompensation [9]. Pathological changes in brain myelin are common, especially in infants who die early in life. The fundamental... 

Amino acid metabolism is important in all tissues/organs but especially so in the liver, intestine, skeletal muscle, adipose tissue, kidney, lung, brain, cells in the bone marrow and cells of the immune system. 

Folate play an important role in the biosynthesis of DNA bases and in amino acid metabolism. An adeguate intake of folate reduces the risk of abnormalities in early embryonic brain development, specifically the risk of malformations of the embryonic brain/spinal cord. Therefore a proper intake is strictly recommended for pregnant women. Megaloblastic anemia is the ultimate consequence of an inadequate folate intake. No adverse effects have been associated with the consumption of excess folate from foods [417]. 

This transfer of reducing equivalents is essential for maintaining the favorable NAD+/NADH ratio required for the oxidative metabolism of glucose and synthesis of glutamate in brain (McKenna et al., 2006). The malate-aspartate shuttle is considered the most important shuttle in brain. It is particularly important in neurons. It has low activity in astrocytes. This shuttle system is fully reversible and linked to amino acid metabolism with the energy charge and citric acid cycle of neuronal cells. 

Primary carnitine deficiency is caused by a deficiency in the plasma-membrane carnitine transporter. Intracellular carnitine deficiency impairs the entry of long-chain fatty acids into the mitochondrial matrix. Consequently, long-chain fatty acids are not available for p oxidation and energy production, and the production of ketone bodies (which are used by the brain) is also impaired. Regulation of intramitochondrial free CoA is also affected, with accumulation of acyl-CoA esters in the mitochondria. This in turn affects the pathways of intermediary metabolism that require CoA, for example the TCA cycle, pyruvate oxidation, amino acid metabolism, and mitochondrial and peroxisomal -oxidation. Cardiac muscle is affected by progressive cardiomyopathy (the most common form of presentation), the CNS is affected by encephalopathy caused by hypoketotic hypoglycaemia, and skeletal muscle is affected by myopathy. 

Examples of the sulfhydryl-dependent enzymes include adenyl cyclase and aminotransferases. Adenyl cyclase catalyzes the conversion of ATP to cyclic AMP needed in brain neurotransmission. Aminotransferases are involved in transamination and thus important in amino acid metabolism. 

J8. Jonxis, J. H. P., Hereditary disorders in the amino-acid metabolism which cause disorders in the central nervous system. In Brain Damage by Inborn Errora of Metabolism, Symp. Interdisciplinary Soc. Biol. Psychiat. pp. 9-22. Bohn, Haarlem, 1968. 

Phenylketonuria, caused by a deficiency of phenylalanine hydroxylase, is one of the most common genetic diseases associated with amino acid metabolism. If this condition is not identified and treated immediately after birth, mental retardation and other forms of irreversible brain damage occur. This damage results mostly from the accumulation of phenylalanine. (The actual mechanism of the damage is not understood.) When it is present in excess, phenylalanine undergoes transamination to form phenylpyruvate, which is also converted to phenyllactate and phenyl-acetate. Large amounts of these molecules are excreted in the urine. Phenylacetate gives the urine its characteristic musty odor. Phenylketonuria is treated with a low-phenylalanine diet. 

The uses of GC to study enzymatic reactions in the amino acid metabolism have also been common. In such studies, measuring either a decreasing substrate concentration or an increase of the reaction product, GC can frequently offer greater sensitivity than other analytical methods. Alternatively, stereospecificity of some enzymatic reactions can be distinguished [505] if the resolution of optical isomers through GC is employed. Recent examples of the enzyme activity determinations are those concerning tryptophan pyrolase [506] and glutamic acid decarboxylase [507] in brain tissue. 

The most Important use of body odors in disease diagnosis relates to the infant diseases involving errors in amino acid metabolism. Strong and unusual odors are manifest in the breath, sweat, and urine of these individuals. Table II summarizes several known acidurias, the amino acids that are not properly metabolized, and the odors associated with the compounds which accumulate and can be detected in the urine ( ). In the case of the Maple Syrup Urine and Oasthouse syndrome, the keto- and hydroxy- acids which have been identified may not be responsible for the observed maple and celery/yeast odors (.9). Alternatively, these odors could be the result of conversion of 2-keto-butyrlc acid to methyl-ethyl-tetronlc acid (Slusser s lactone) which is used as an extender in maple and celery flavors and has a maple syrup-like odor (R. Soukup, personal communication). With these acidurias it is imperative that an immediate diagnosis is made, since corrective diet can prevent the brain damage that results from these diseases. This is readily done on an olfactory basis which can subsequently be supported by gas chromatographic... 

In PKU, similarly as in the other inherited disorders of amino acid metabolism, the fast growing brain of the fetus is protected by the mother s enzymatic activity. The disturbances appear after birth, and the central nervous system is at risk of damage until the brain is fully developed and matured [42]. Despite the fact that the increase in brain mass and the creation of synaptic connections occurs mainly during the first year of life, the full development of some areas (e.g., prefrontal cortex or white matter myelination) is not complete until adulthood (Box 9.4). 

Minchin M. C W and Beart P M. (1974) Compartmentation of amino acid metabolism in the rat dorsal ganglia A metabolic and autoradiographic study. Brain Res, S3, 437-449. 

Mukherjee, a., and P. K. Dey Changes in Amino Acid Metabolism in Rat Brain Following Glycosine Administration. Indian J. Exp. Biol. 8, 263 (1970). 

Folate is involved in one-carbon unit transfer reactions during DNA synthesis, DNA methylation, and amino acid metabolism. Evidence to date shows that maternal dietary intake of folic acid is inversely associated with the risk of neural tube defect-affeeted pregnancies [9,10]. Neural tube defects (a term which includes spina bifida) are anatomieal birth anomalies affecting the brain and the spinal cord. As a result of these landmark findings, the first folic acid fortification program was introduced in the United States during 1998, in an attempt to reduce the prevalence... 

The accumulation of phenylalanine and its metabolites may interfere with the metabolism of other amino acids. Stein and Moore, and later Knox, showed that in phenylketonuric patients the amount of other amino acids in the plasma is decreased while phenylalanine accumulates. This interaction between the amino acids metabolism acquires particular significance in view of the mode of amino acid uptake in the brain. The investigators demonstrated that phenylalanine inhibits tyrosine uptake in the brain. Thus, in the presence of large amounts of phenylalanine, protein synthesis in the brain might be inhibited. Furthermore, because of the absence of tyrosine, the biosynthesis of well-known neuroregulators derived from tyrosine, such as norepinephrine and 3,4-dihydroxyphenylethyl-amine, could also be reduced in the brain. 

King MW. Introduction to Amino Acid Metabolism. lU School of Medicine, 2006. http //www.indstate.edU/thcme/mwking/amino-acid-metabolism.html tyrosine. Deijen JB, Orlebeke JF. Effect of tyrosine on cognitive function and blood pressure under stress. Brain Res Bull 1994 33 319-323. 

In vivo deuterium ( H) MRS has been used to characterize amino acid metabolism, body iron content, brain and kidney metabolism and body fat utilization rates in rodents. These studies rely on the use of deuterium labelling or the existence of natural-abundance deuterium in water or lipids. For example, deuterium-labelled methionine was used to confirm the dominant contribution of the glycine/ sarcosine shuttle to the metabolism of excess methionine, while deuterium-labelled glucose was used to show that systemic glucose level influences brain... 

A number of other rare disturbances of aromatic amino acid metabolism associated with mental defect and usually with evidence of inheritance have been reported (see ref. 419 for review) and might well also lead to disturbed brain amine metabolism, e.g. tyrosinaemia, increased urinary dopa with dwarfism, tryptophanuria, hydroxykynureninuria and hyper-calcaemia with indicanuria. 

EtsSn- Intoxication and effect on P phospholipides and body temperature (3) effect on amino acid metabolism in brain cortex slices (99) effect on platelet shape and aggregation (UOTf, 104 7), effect on platelet morphology (2781), effect on oxidation of glucose and pyruvate in brain cortex slices (916) effect on brain glucose metabolism in vivo and vitro (9I8), effect on retention of potassitmi and amino acid in brain cortex slices (917)-... 

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