Amino acid metabolism transport

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

Other Toxicity Concerns. Additional toxicity concerns include interference with normal metabolism and function of mucosal cells, for example, water absorption by these cells [80]. The unconjugated bile acids are known to block amino acid metabolism [81] and glucose transport [82]. There is a possibility of biotransformation of these enhancers to toxic or carcinogenic substances by hepatic monooxygenases [83]. Absorption of permeation enhancers into the systemic circulation can also cause toxicity, for example, azone [84] and hexamethylene lauramide [85] which are absorbed... 

Pyridoxal phosphate is a required coenzyme for many enzyme-catalyzed reactions. Most of these reactions are associated with the metabolism of amino acids, including the decarboxylation reactions involved in the synthesis of the neurotransmitters dopamine and serotonin. In addition, pyridoxal phosphate is required for a key step in the synthesis of porphyrins, including the heme group that is an essential player in the transport of molecular oxygen by hemoglobin. Finally, pyridoxal phosphate-dependent reactions link amino acid metabolism to the citric acid cycle (chapter 16). 

Amino acid metabolism occurs within the cell but, before this can occur, the amino acids must be transported across the plasma membrane. This requires transport proteins, which have three important characteristics ... 

In individuals with PKU, a secondary, normally little-used pathway of phenylalanine metabolism comes into play. In this pathway phenylalanine undergoes transamination with pyruvate to yield phenylpyruvate (Fig. 18-25). Phenylalanine and phenylpyruvate accumulate in the blood and tissues and are excreted in the urine—hence the name phenylketonuria. Much of the phenylpyruvate, rather than being excreted as such, is either decarboxylated to phenylacetate or reduced to phenyllactate. Phenylacetate imparts a characteristic odor to the urine, which nurses have traditionally used to detect PKU in infants. The accumulation of phenylalanine or its metabolites in early life impairs normal development of the brain, causing severe mental retardation. This may be caused by excess phenylalanine competing with other amino acids for transport across the blood-brain barrier, resulting in a deficit of required metabolites. 

Glutamine synthetase is found in all organisms. In addition to its importance for NHj assimilation in bacteria, it has a central role in amino acid metabolism in mammals, converting toxic free NHj to glutamine for transport in the blood (Chapter 18). 

Incidence of inherited diseases of amino acid metabolism. [Note Cystinuria is the most common genetic error of amino acid transport.]... 

FIGURE 7 Top-scored metabolite-centric network generated by Ingenuity Pathway Analysis (IPA) describing amino acid metabolism, molecular transport, and small-molecule biochemistry. Microarray results were overlaid in the network highlighting associations between metabolites and transcripts in different canonical pathways (CP). Underlined molecules were downregulated not underlined molecules were upregulated Alp, p70 S6k, and AMPK (marked with an asterisk) were not altered. Reproduced from Ref. (20). 

Related topics Myoglobin and hemoglobin (B4) Photosynthesis (L3) Electron transport and oxidative Amino acid metabolism (M2) phosphorylation (L2)... 

Throughout this chapter, we have had occasion to refer to genetic diseases associated with amino acid metabolism. Such defects are characterized by amino acidemias and amino acidurias. The former indicate elevated amino acid levels in serum, whereas the latter indicate their excretion in the urine. A patient may have an amino aciduria without an amino acidemia. This is the case with amino acid transport disorders. It is unusual, however, to have an amino acidemia without amino aciduria. 

Wellner D, Meister A. A survey of inborn errors of amino acid metabolism and transport in man. Annu Rev Biochem 50 911-968, 1981. 

The mitochondrion, in addition to being the powerhouse of the cell (because it generates more than 90% of the ATP used by the cell), is also the site of fatty acid oxidation, the tricarboxylic acid (TCA) cycle, electron transport, and amino acid metabolism. Central to the utilization of fuel molecules—carbohydrates, pro-... 

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. 

The protein and amino-acid metabolism of the liver is characterized by three essential functions (1.) production and breakdown of proteins, (2.) production and breakdown of amino acids as well as regulation of their concentrations in the blood, and (i.) detoxification of ammonium via the synthesis of urea (= excretory form) and glutamine (= non-toxic transport or storage form) with simultaneous regulation of the acid-base balance. The breakdown of branched-chain amino acids occurs only in the musculature by way of deamination, (s. pp 38, 43)... 

Aminoacidurias may be primary or secondary. Primary disease is due to an inherited enzyme defect, also called an inborn error of metabolism. The defect is located either in the pathway by which a specific amino acid is metabolized or in the specific renal tubular transport system by which the amino acid is reabsorbed. Secondary aminoaciduria is due to disease of an organ, such as the liver, which is an active site of amino acid metabolism, or to generalized renal tubular dysfunction, or to protein-energy malnutrition. Specific inborn errors of metabohsm are discussed in more detail in Chapter 55. 

Table 55-2 shows a summary of known disorders of amino acid metabolism and transport, including information about their incidence, major clinical features and biochemical patterns, availabitity of prenatal diagnosis and newborn screening, and association with sudden unexpected death. Several of these disorders are discussed next. 

PIHH syndrome. 238970 Mitochondrial ornithine transporter MisceUaneous Disorders of Amino Acid Metabolism <1 100,000. Mental retardation,. seizures, pyramidal signs, compromised. sense of vibration. . v ... 

Scriver, C. R., Schafer, I. A., and Efron, M. L., New renal tubular amino-acid transport system and a new hereditary disorder of amino acid metabolism. Nature (London) 192, 672-673 (1961). 

Aranda, A. and del Olmo, M. 2004. Exposure of Saccharomyces cerevisiae to acetaldehyde induces sulfur amino acid metabolism and polyamine transporter genes, which depend on Met4p and Haalp transcription factors, respectively. Appl. Environ. Microbiol. 70, 1913-1922. 

Intracellular metabolism of amino acids requires their transport across the cell membrane. Transport of L-amino acids occurs against a concentration gradient and is an active process usually coupled to Na -dependent carrier systems as for transport of glucose across the intestinal mucosa (Chapter 12). At least five transport systems for amino acids (with overlapping specificities) have been identified in kidney and intestine. They transport neutral amino acids, acidic amino acids, basic amino acids, ornithine and cystine, and glycine and proline, respectively. Within a given carrier system, amino acids may compete for transport (e.g., phenylalanine with tryptophan). Na+-independent transport carriers for neutral and lipophilic amino acids have also been described, d-Amino acids are transported by simple diffusion favored by a concentration gradient. 

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