Skip to main content
SpringerLink
Log in

Interpretation of plasma amino acids in the follow-up of patients: The impact of compartmentation

  • EMG Lecture
  • Published:
Journal of Inherited Metabolic Disease

Summary

Results of plasma or urinary amino acids are used for suspicion, confirmation or exclusion of diagnosis, monitoring of treatment, prevention and prognosis in inborn errors of amino acid metabolism. The concentrations in plasma or whole blood do not necessarily reflect the relevant metabolite concentrations in organs such as the brain or in cell compartments; this is especially the case in disorders that are not solely expressed in liver and/or in those which also affect nonessential amino acids. Basic biochemical knowledge has added much to the understanding of zonation and compartmentation of expressed proteins and metabolites in organs, cells and cell organelles. In this paper, selected old and new biochemical findings in PKU, urea cycle disorders and nonketotic hyperglycinaemia are reviewed; the aim is to show that integrating the knowledge gained in the last decades on enzymes and transporters related to amino acid metabolism allows a more extensive interpretation of biochemical results obtained for diagnosis and follow-up of patients and may help to pose new questions and to avoid pitfalls. The analysis and interpretation of amino acid measurements in physiological fluids should not be restricted to a few amino acids but should encompass the whole quantitative profile and include other pathophysiological markers. This is important if the patient appears not to respond as expected to treatment and is needed when investigating new therapies. We suggest that amino acid imbalance in the relevant compartments caused by over-zealous or protocol-driven treatment that is not adjusted to the individual patient’s needs may prolong catabolism and must be corrected.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Appel SH (1966) Inhibition of brain protein synthesis: an approach to the biochemical basis of neurological dysfunction in the amino-acidurias. Trans N Y Acad Sci 29: 63–70.

    PubMed  CAS  Google Scholar 

  • Applegarth DA, Toone JR (2001) Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis. Mol Genet Metab 74: 139–146.

    Article  PubMed  CAS  Google Scholar 

  • Bachmann C (1992) Ornithine carbamoyl transferase deficiency: findings, models and problems. J Inherit Metab Dis 15: 578–591.

    Article  PubMed  CAS  Google Scholar 

  • Bachmann C (2002) Mechanisms of hyperammonemia. Clin Chem Lab Med 40: 653–662.

    Article  PubMed  CAS  Google Scholar 

  • Bachmann C (2007) Hyperammonemia: Review of current treatment strategies. In: Bachmann C, Häberle J, Leonard J, eds. Pathophysiology and Management of Hyperammonaemia. Heilbronn: SPS Verlagsgesellschaft, 157–173.

    Google Scholar 

  • Bachmann C, Mihatsch MJ, Baumgartner RE et al (1971) Non-ketotic hyperglycinemia: peracute course in neonatal period. Helv Paediatr Acta 26: 228–243.

    PubMed  CAS  Google Scholar 

  • Bak LK, Schousboe A, Waagepetersen HS (2006) The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem 98: 641–653.

    Article  PubMed  CAS  Google Scholar 

  • Batshaw ML, MacArthur RB, Tuchman M (2001) Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatr 138: S46–54; discussion S54–45.

    Article  PubMed  CAS  Google Scholar 

  • Berger V, Larondelle Y, Trouet A, Schneider YJ (2000) Transport mechanisms of the large neutral amino acid l-phenylalanine in the human intestinal epithelial Caco-2 cell line. J Nutr 130: 2780–2788.

    PubMed  CAS  Google Scholar 

  • Bhattacharya K, Briddon A, Lee P (2007) A review of biochemical outcomes of adults with OTC deficiency. J Inherit Metab Dis 30: 82.

    Article  CAS  Google Scholar 

  • Bixel MG, Shimomura Y, Hutson SM, Hamprecht B (2001) Distribution of key enzymes of branched-chain amino acid metabolism in glial and neuronal cells in culture. J Histochem Cytochem 49: 407–418.

    PubMed  CAS  Google Scholar 

  • Blaheta RA, Cinatl J Jr (2002) Anti-tumor mechanisms of valproate: a novel role for an old drug. Med Res Rev 22: 492–511.

    Article  PubMed  CAS  Google Scholar 

  • Brosnan JT, Brosnan ME (2006) Branched-chain amino acids: enzyme and substrate regulation. J Nutr 136: 207–211.

    Google Scholar 

  • Bruhat A, Jousse C, Fafournoux P (1999) Amino acid limitation regulates gene expression. Proc Nutr Soc 58: 625–632.

    PubMed  CAS  Google Scholar 

  • Calvaruso G, Carabillo M, Giuliano M et al (2001) Sodium phenylbutyrate induces apoptosis in human retinoblastoma Y79 cells: the effect of combined treatment with the topoisomerase I-inhibitor topotecan. Int J Oncol 18: 1233–1237.

    PubMed  CAS  Google Scholar 

  • Camacho LH, Olson J, Tong WP, Young CW, Spriggs DR, Malkin MG (2007) Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors. Investigational New Drugs 25: 131–138.

    Article  PubMed  CAS  Google Scholar 

  • Chang TH, Szabo E (2002) Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-gamma and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin Cancer Res 8: 1206–1212.

    PubMed  CAS  Google Scholar 

  • Chang TW, Goldberg AL (1978) The origin of alanine produced in skeletal muscle. J Biol Chem 253: 3677–3684.

    PubMed  CAS  Google Scholar 

  • Chen N, Reith M, Quick M (2004) Synaptic uptake and beyond: the sodium- and chloride dependent neurotransmitter transporter family SLC6. Pflügers Arch Eur J Physiol 447: 519–531.

    Article  CAS  Google Scholar 

  • Codogno P, Meijer AJ (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12: 1509–1518.

    Article  PubMed  CAS  Google Scholar 

  • Curthoys NP, Watford M (1995) Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr 15: 133–159.

    Article  PubMed  CAS  Google Scholar 

  • Darmaun D, Welch S, Rini A, Sager BK, Altomare A, Haymond MW (1998) Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism. Am J Physiol Endocrinol Metab 274: 801–807.

    Google Scholar 

  • Diezel PB, Martin K (1966) Hyperglycinemia (glycinosis) with familial idiopathic hyperglycinuria. 1st observation in Germany. Dtsch Med Wochenschr 91: 2249–2254.

    Article  PubMed  CAS  Google Scholar 

  • Dingemanse MA, De Jonge WJ, De Boer PAJ, Mori M, Lamers WH, Moorman AF (1996) Development of the ornithine cycle in rat liver: Zonation of a metabolic pathway. Hepatology 24: 407–411.

    Article  PubMed  CAS  Google Scholar 

  • Endo Y, Fu Z, Abe K, Arai S, Kato H (2002) Dietary protein quantity and quality affect rat hepatic gene expression 1. J Nutr 132: 3632–3637.

    PubMed  CAS  Google Scholar 

  • Eulenburg V, Armsen W, Betz H, Gomeza J (2005) Glycine transporters: essential regulators of neurotransmission. Trends Biochem Sci 30: 325–333.

    Article  PubMed  CAS  Google Scholar 

  • Gebhardt R, Baldysiak-Figiel A, Krugel V, Ueberham E, Gaunitz F (2007) Hepatocellular expression of glutamine synthetase: An indicator of morphogen actions as master regulators of zonation in adult liver. Prog Histochem Cytochem 41: 201–266.

    Article  PubMed  CAS  Google Scholar 

  • Gitzelmann R, Steinmann B, Otten A et al (1978) Nonketotic hyperglycinemia treated with strychnine, a glycine receptor antagonist. Helv Paediatr Acta 32: 517–525.

    PubMed  CAS  Google Scholar 

  • Gottlicher M (2004) Valproic acid: an old drug newly discovered as inhibitor of histone deacetylases. Ann Hemat 83(Supplement 1): S91–92.

    Google Scholar 

  • Güttler F, Lou H (1986) Dietary problems of phenylketonuria: effect on CNS transmitters and their possible role in behaviour and neuropsychological function. J Inherit Metab Dis 9: 169–177.

    Article  PubMed  Google Scholar 

  • Hall TR, Wallin R, Reinhart GD, Hutson SM (1993) Branched chain aminotransferase isoenzymes. Purification and characterization of the rat brain isoenzyme. J Biol Chem 268: 3092–3098.

    PubMed  CAS  Google Scholar 

  • Hankard RG, Darmaun D, Sager BK, D’Amore D, Parsons WR, Haymond M (1995) Response of glutamine metabolism to exogenous glutamine in humans. Am J Physiol Endocrinol Metab 269: 663–670.

    Google Scholar 

  • Harris DJ, Thompson RM, Wolf B, Yang BI (1981) Propionyl coenzyme A carboxylase deficiency presenting as non-ketotic hyperglycinaemia. J Med Genet 18: 156–157.

    Article  CAS  Google Scholar 

  • Harris TE, Chi A, Shabanowitz J, Hunt DF, Rhoads RE, Lawrence JC Jr (2006) mTOR-dependent stimulation of the association of eIF4G and eIF3 by insulin. EMBO J 25: 1659–1668.

    Article  PubMed  CAS  Google Scholar 

  • Häussinger D (1983) Hepatocyte heterogeneity in glutamine and ammonia metabolism and the role of an intercellular glutamine cycle during ureogenesis in perfused rat liver. Eur J Biochem 133: 269–275.

    Article  PubMed  Google Scholar 

  • Hawkins RA, O’Kane RL, Simpson IA, Vina JR (2006) Structure of the blood–brain barrier and its role in the transport of amino acids. J Nutr 136: 218–226.

    Google Scholar 

  • Huisman T, Thiel T, Steinmann B, Zeilinger G, Martin E (2002) Proton magnetic resonance spectroscopy of the brain of a neonate with nonketotic hyperglycinemia: in vivo–in vitro (ex vivo) correlation. Eur Radiol 12: 858–861.

    Article  PubMed  CAS  Google Scholar 

  • Hutson SM, Berkich D, Drown P, Xu B, Aschner M, LaNoue KF (1998) Role of branched-chain aminotransferase isoenzymes and gabapentin in neurotransmitter metabolism. J Neurochem 71: 863–874.

    Article  PubMed  CAS  Google Scholar 

  • Hutson SM, Lieth E, LaNoue KF (2001) Function of leucine in excitatory neurotransmitter metabolism in the central nervous system. J Nutr 131: 846–850.

    Google Scholar 

  • Hutson SM, Wallin R, Hall TR (1992) Identification of mitochondrial branched chain aminotransferase and its isoforms in rat tissues. J Biol Chem 267: 15681–15686.

    PubMed  CAS  Google Scholar 

  • Islam M, Wallin R, Wynn RM et al (2007) A novel branched-chain amino acid metabolon: protein–protein interactions in a supramolecular complex. J Biol Chem 282: 11893–11903.

    Article  PubMed  CAS  Google Scholar 

  • Isojärvi J, Laatikainen TJ, Pakarinen AJ, Juntunen K, Myllylä VV (1993) Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 329: 1383–1388.

    Article  PubMed  Google Scholar 

  • Jones JG, Solomon MA, Sherry AD, Jeffrey FMH, Malloy CR (1998) 13C NMR measurements of human gluconeogenic fluxes after ingestion of [U-13C] propionate, phenylacetate, and acetaminophen. Am J Physiol Endocrinol Metab 275: 843–852.

    Google Scholar 

  • Jousse C, Bruhat A, Ferrara M, Fafournoux P (1998) Physiological concentration of amino acids regulates insulin-like-growth-factor-binding protein 1 expression. Biochem J 334: 147–153.

    PubMed  CAS  Google Scholar 

  • Jungermann K, Kietzmann T (1996) Zonation of parenchymal and nonparenchymal metabolism in liver. Annu Rev Nutr 16: 179–203.

    Article  PubMed  CAS  Google Scholar 

  • Kanai Y, Hediger MA (2004) The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Pflügers Arch Eur J Physiol 447: 469–479.

    Article  CAS  Google Scholar 

  • Kanamori K, Ross BD (2004) Quantitative determination of extracellular glutamine concentration in rat brain, and its elevation in vivo by system A transport inhibitor, alpha-(methylamino) isobutyrate. J Neurochem 90: 203–210.

    Article  PubMed  CAS  Google Scholar 

  • Kanamori K, Ross BD (2005) Suppression of glial glutamine release to the extracellular fluid studied in vivo by NMR and microdialysis in hyperammonemic rat brain. J Neurochem 94: 74–85.

    Article  PubMed  CAS  Google Scholar 

  • Kanamori K, Ross BD, Kondrat RW (1998) Rate of glutamate synthesis from leucine in rat brain measured in vivo by 15 N NMR. J Neurochem 70: 1304–1315.

    Article  PubMed  CAS  Google Scholar 

  • Koch R, Moseley KD, Yano S, Nelson Jr M, Moats RA (2003) Large neutral amino acid therapy and phenylketonuria: a promising approach to treatment. Mol Genet Metab 79: 110–113.

    Article  PubMed  CAS  Google Scholar 

  • Korman SH, Gutman A (2002) Pitfalls in the diagnosis of glycine encephalopathy (non-ketotic hyperglycinemia). Dev Med Child Neurol 44: 712–720.

    Article  PubMed  Google Scholar 

  • Labow BI, Souba WW, Abcouwer SF (2001) Mechanisms governing the expression of the enzymes of glutamine metabolism—glutaminase and glutamine synthetase. J Nutr 131: 2467S–2474S; discussion 2486S–2467S.

    PubMed  CAS  Google Scholar 

  • Lea MA, Sura M, Desbordes C (2004) Inhibition of cell proliferation by potential peroxisome proliferator-activated receptor (PPAR) gamma agonists and antagonists. Anticancer Res 24: 2765–2771.

    PubMed  CAS  Google Scholar 

  • Lee WJ, Hawkins RA, Peterson DR, Vina JR (1996) Role of oxoproline in the regulation of neutral amino acid transport across the blood–brain barrier. J Biol Chem 271: 19129.

    Article  PubMed  CAS  Google Scholar 

  • Leweling H, Breitkreutz R, Behne F, Staedt U, Striebel JP, Holm E (1996) Hyperammonemia-induced depletion of glutamate and branched-chain amino acids in muscle and plasma. J Hepatol 25: 756–762.

    Article  PubMed  CAS  Google Scholar 

  • Lou HC, Güttler F, Lykkelund C, Bruhn P, Niederwieser A (1985) Decreased vigilance and neurotransmitter synthesis after discontinuation of dietary treatment for phenylketonuria in adolescents. Eur J Pediatr 144: 17–20.

    Article  PubMed  CAS  Google Scholar 

  • Mackenzie B, Erickson JD (2004) Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflügers Arch Eur J Physiol 447: 784–795.

    Article  CAS  Google Scholar 

  • Maestri NE, Clissold DB, Brusilow SW (1995) Long-term survival of patients with argininosuccinate synthetase deficiency. J Pediatr 127: 929–935.

    Article  PubMed  CAS  Google Scholar 

  • Maestri NE, Clissold D, Brusilow SW (1999) Neonatal onset ornithine transcarbamylase deficiency: a retrospective analysis. J Pediatr 134: 268–272.

    Article  PubMed  CAS  Google Scholar 

  • Marcaggi P, Coles JA (2001) Ammonium in nervous tissue: transport across cell membranes, fluxes from neurons to glial cells, and role in signalling. Prog Neurobiol 64: 157–183.

    Article  PubMed  CAS  Google Scholar 

  • Matalon R, Surendran S, Matalon KM et al (2003) Future role of large neutral amino acids in transport of phenylalanine into the brain. Pediatr 112: 1570–1574.

    Google Scholar 

  • Matalon R, Michals-Matalon K, Bhatia G et al (2006) Large neutral amino acids in the treatment of phenylketonuria (PKU). J Inherit Metab Dis 29: 732–738.

    Article  PubMed  CAS  Google Scholar 

  • Matalon R, Michals-Matalon K, Bhatia G et al (2007) Double blind placebo control trial of large neutral amino acids in treatment of PKU: Effect on blood phenylalanine. J Inherit Metab Dis 30: 153–158.

    Google Scholar 

  • Mehnert JM, Kelly WK (2007) Histone deacetylase inhibitors: biology and mechanism of action. Cancer J 13: 23–29.

    PubMed  CAS  Google Scholar 

  • Meijer AJ, Dubbelhuis PF (2004) Amino acid signalling and the integration of metabolism. Biochem Biophys Res Commun 313: 397–403.

    Article  PubMed  CAS  Google Scholar 

  • Miller LP, Pardridge WM, Braun LD, Oldendorf WH (1985) Kinetic constants for blood-brain barrier amino acid transport in conscious rats. J Neurochem 45: 1427–1432.

    Article  PubMed  CAS  Google Scholar 

  • Miyanaka K, Gotoh T, Nagasaki A et al (1998) Immunohistochemical localization of arginase II and other enzymes of arginine metabolism in rat kidney and liver. Histochem J 30: 741–751.

    Article  PubMed  CAS  Google Scholar 

  • Morris AAM, Leonard JV (1997) Early recognition of metabolic decompensation. Arch Dis Child 76: 555–556.

    PubMed  CAS  Google Scholar 

  • Nishitani S, Ijichi C, Takehana K, Fujitani S, Sonaka I (2004) Pharmacological activities of branched-chain amino acids: specificity of tissue and signal transduction. Biochem Biophys Res Commun 313: 387–389.

    Article  PubMed  CAS  Google Scholar 

  • Nissim I (1999) Newer aspects of glutamine/glutamate metabolism: the role of acute pH changes. Am J Physiol 277: 493–497.

    Google Scholar 

  • Novotny EJ, Fulbright RK, Pearl PL, Gibson KM, Rothman DL (2003) Magnetic resonance spectroscopy of neurotransmitters in human brain. Ann Neurol 54: S25–S31.

    Article  PubMed  CAS  Google Scholar 

  • Oldendorf WH, Sisson BW, Silverstein A (1971) Brain uptake of selenomethionine Se 75. II. Reduced brain uptake of selenomethionine Se 75 in phenylketonuria. Arch Neurol 24: 524–528.

    PubMed  CAS  Google Scholar 

  • Orlowski J, Grinstein S (2004) Diversity of the mammalian sodium/proton exchanger SLC9 gene family. Pflügers Arch Eur J Physiol 447: 549–565.

    Article  CAS  Google Scholar 

  • Owen OE (1998) Protein, fat, and carbohydrate requirements during starvation: anaplerosis and cataplerosis]. J Nutr 68: 12–34.

    CAS  Google Scholar 

  • Palacin M, Yoshikatsu K (2004) The ancillary proteins of HATs: SLC3 family of amino acid transporters. Pflügers Arch Eur J Physiol 447: 490–494.

    Article  CAS  Google Scholar 

  • Palmieri F (2004) The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflügers Arch Eur J Physiol 447: 689–709.

    Article  CAS  Google Scholar 

  • Perry TL, Hansen S, Berry K, Mok C, Lesk D (1971) Free amino acids and related compounds in biopsies of human brain. J Neurochem 18: 521–528.

    Article  PubMed  CAS  Google Scholar 

  • Perry TL, Urquhart N, MacLean J et al (1975) Nonketotic hyperglycinemia. Glycine accumulation due to absence of glycerine cleavage in brain. N Engl J Med 292: 1269–1273.

    Article  PubMed  CAS  Google Scholar 

  • Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 276: 36734–36741.

    Article  PubMed  CAS  Google Scholar 

  • Pichili VB, Rao KV, Jayakumar AR, Norenberg MD (2007) Inhibition of glutamine transport into mitochondria protects astrocytes from ammonia toxicity. Glia 55: 801–809.

    Article  PubMed  CAS  Google Scholar 

  • Pietz J, Kreis R, Rupp A et al (1999) Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria. J Clin Invest 103: 1169–1178.

    Article  PubMed  CAS  Google Scholar 

  • Plaitakis A, Spanaki C, Mastorodemos V, Zaganas I (2003) Study of structure-function relationships in human glutamate dehydrogenases reveals novel molecular mechanisms for the regulation of the nerve tissue-specific (GLUD2) isoenzyme. Neurochem Int 43: 401–410.

    Article  PubMed  CAS  Google Scholar 

  • Proud CG (2004a) mTOR-mediated regulation of translation factors by amino acids. Biochem Biophys Res Commun 313: 429–436.

    Article  CAS  Google Scholar 

  • Proud CG (2004b) Role of mTOR signalling in the control of translation initiation and elongation by nutrients. Curr Top Microbiol Immunol 279: 215–244.

    CAS  Google Scholar 

  • Rennie MJ, Wackerhage H, Spangenburg EE, Booth FW (2004) Control of the size of the human muscle mass. Ann Rev Physiol 66: 799–828.

    Article  CAS  Google Scholar 

  • Scaglia F, Carter S, O’Brien WE, Lee B (2004) Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients. Mol Genet Metab 81: S79–85.

    Article  PubMed  CAS  Google Scholar 

  • Scaglia F, Lanpher B, Marinim J, Lee B (2007) Role of branched chain amino acids in patients with urea cycle disorders. In: Bachmann C, Häberle J, Leonard J, eds. Pathophysiology and Management of Hyperammonaemia. Heilbronn: SPS Verlagsgesellschaft, 157–173.

    Google Scholar 

  • Shih V (2003) Amino acid analysis. In: Blau N, Duran M, Blaskovics M, Gibson M, eds. Physician’s Guide to the Laboratory Diagnosis of Metabolic Diseases. Berlin: Springer-Verlag, 11–26.

    Google Scholar 

  • Summar M (2001) Current strategies for the management of neonatal urea cycle disorders. J Pediatr 138: S30–39.

    Article  PubMed  CAS  Google Scholar 

  • Sweatt AJ, Garcia-Espinosa MA, Wallin R, Hutson SM (2004) Branched-chain amino acids and neurotransmitter metabolism: Expression of cytosolic branched-chain aminotransferase(BCATc) in the cerebellum and hippocampus. J Comp Neurol 477: 360–370.

    Article  PubMed  CAS  Google Scholar 

  • Tada K, Kure S (2005) Nonketotic hyperglycinemia: Pathophysiological studies. Proc Japan Acad 81: 411–417.

    Article  CAS  Google Scholar 

  • Taub F, Johnson TC (1975) The mechanism of polyribosome disaggregation in brain tissue by phenylalanine. Biochem J 151: 173–180.

    PubMed  CAS  Google Scholar 

  • Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y (2004) CATs and HATs: the SLC7 family of amino acid transporters. Pflügers Arch Eur J Physiol 447: 532–542.

    Article  CAS  Google Scholar 

  • von Wendt L, Simila S, Saukkonen AL, Koivisto M (1980) Failure of strychnine treatment during the neonatal period in three Finnish children with nonketotic hyperglycinemia. Pediatrics 65: 1166–1169.

    Google Scholar 

  • Welbourne TC (1987) Interorgan glutamine flux in metabolic acidosis. Am J Physiol 253: F1069-1076.

    Google Scholar 

  • Whitehead KJ, Pearce SM, Walker G, Sundaram H, Hill D, Bowery NG (2004) Positive N-methyl-d-aspartate receptor modulation by selective glycine transporter-1 inhibition in the rat dorsal spinal cord in vivo. Neuroscience 126: 381–390.

    Article  PubMed  CAS  Google Scholar 

  • Wilson CJ, Lee PJ, Leonard JV (2001) Plasma glutamine and ammonia concentrations in ornithine carbamoyltransferase deficiency and citrullinaemia. J Inherit Metab Dis 24: 691–695.

    Article  PubMed  CAS  Google Scholar 

  • Xin X, Yang S, Kowalski J, Gerritsen ME (1999) Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 274: 9116–9121.

    Article  PubMed  CAS  Google Scholar 

  • Yoshizawa F (2004) Regulation of protein synthesis by branched-chain amino acids in vivo. Biochem Biophys Res Commun 313: 417–422.

    Article  PubMed  CAS  Google Scholar 

  • Yudkoff M, Daikhin Y, Nissim I et al (2005) Brain amino acid requirements and toxicity: the example of leucine. JNutr 135: 1531–1538.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Chemistry, University of Lausanne, Lausanne, Switzerland

    Claude Bachmann

  2. Rittergasse 11, CH 4103, Bottmingen, Switzerland

    Claude Bachmann

Authors
  1. Claude Bachmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claude Bachmann.

Additional information

Communicating editor: Georg Hoffmann

Competing interests: None declared

This paper is based in the European Metabolic Group (EMG) Lecture given at the 39th EMG Meeting in Warsaw on 3 June 2007 - organized and sponsored by Milupa Metabolics.

References to electronic databases: Phenylketonuria: OMIM 262600. Urea cycle enzymes, mitochondrial: EC 2.3.1.1, 2.1.3.3, 6.3.4.16. Urea cycle enzymes, cytosolic: EC 3.5.3.1, 4.3.2.1, 6.3.4.5. HHH syndrome: OMIM 238970. Citrin deficiency: OMIM 603859. Lysinuric protein intolerance: OMIM 222700. Branched-chain aminotransferase: EC 2.6.1.42. Non-ketotic hyperglycinaemia: OMIM 605899. Hereditary hyperekplexia: OMIM 149400.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bachmann, C. Interpretation of plasma amino acids in the follow-up of patients: The impact of compartmentation. J Inherit Metab Dis 31, 7–20 (2008). https://doi.org/10.1007/s10545-007-0772-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-007-0772-y

Keywords

Search

Navigation