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Lou et al used Tyr 160 mg/kg in treated patients with PKU Increased attention span Increased dopamine synthesis 1987 Acta Paediatr Scand 76:560 8;6"r!wTyrosine in Treatment of PKU Pietz et al. used high dose tyrosine in adults with PKU and high blood Phe No difference in treated group vs placebo 1995 J Pediatr 127:936 4yy Tryptophan in Treated PKU Nielsen et al used tryptophan 4.5 gm/day to treated PKU for 3 weeks Showed a 3 fold increase in 5-HIAA in CSF despite high blood Phe 1988 Dietary Phenylalanine and Brain Function. Birkhauser 8Z=Z: LNAA Supplementation in PKU Dotremont et al. used LNAA and a low protein diet 0.6 gm/kg on 4 patients with PKU After 1 month subjects found with negative nitrogen balance Lysine was limiting amino acid 1995 J Inherit Metab Dis 18:1270Z!Z  PreKUnil Composition per Tablet Tyrosine 191 mg Tryptophan 65 mg Arginine 35 mg Leucine 35 mg Isoleucine 35 mg Valine 35 mg Methionine 35 mg Threonine 35 mg Lysine 0 mg P# G.8Km (app)  Km (1 + "[aa]/Km]   This predicts that, if the plasma level of an LNAA is much less than its value of Km, then that amino acid will not compete effectively for the carrier proteinJ1E,Neo PheL-Tyrosine 195.0 mg L-Tryptophan 51.0 mg L-Methionine 32.0 mg L-Isolecine 35.0 mg L-Threonine 32.0 mg L-Valine 35.0 mg L-Leucine 130.0 mg L-Histidine 30.0 mg L-Lysine 30.0 mg L-Arginine 30.0 mg  P-LNAA Transport in Intestinal Mucosa Km mmol/L*.%Phenylalanine 1.0 Leucine 2.0 Valine 3.0 Methionine 5.0 Histidine 6.0 Competition effect is not likely to occur in tissue other than brain unless high concentration of amino acids is used 8ZZRuK20Hidalgo Biochem Biophys. Acta 1008: 5-30a (1990)11`?PPKU Mice on NeoPhe Control phe mg/dl NeoPhe:Q@Y9_DDenmark LNAA STUDY$kIDenmark LNAA STUDYmJ Russia LNAA STUDY (nK Russia LNAA Study (oLUSA LNAA STUDY(pMUSA LNAA STUDY\tOS5:US Blood Phe and Tyr NeoPhe Patient K 1 Week mol/L (mg)";/ " T6.US Blood Phe and Tyr NeoPhe Patient G 1 Week// |UNeoPhe 0.5 g/kg in PKU Subjects (13 subjects Mean age 26.6 years 7 males, 6 females Mean decrease in blood Phe after one week 243 mol/L Average decrease in blood Phe 22 %.b+ ,J6VNeoPhe 1.0 g/kg in PKU Subjects (7 subjects Mean age 25.2 years 5 males, 2 females Mean decrease in blood Phe after one week 377 mol/L Average decrease in blood Phe 25 %.a+ ,I6WDFigure 1. Blood Phe Response to 0.5g/kg NeoPhe in Patients with PKU*E@$ $$YEFigure 2. Blood Phe Response to 1.0 g/kg NeoPhe in Patients with PKU*FA$ $$wR CONCLUSIONSFor the first time mixture of LNAA can lower blood phenylalanine Using NeoPhe avoids lysine deficiency Lysine deficiency can lead to negative nitrogen balance and decreased levels of carnitine xSAcknowledgementParticipants in the study Professor Elena Grechanina Kharkiv, Ukraine Professor Peter Novikov Moscow, Russia Dr. Jytte Bieber Nielsen Glostrup, Denmark $PC  0` ` ̙33` 333MMM` ff3333f` f` f` 3>?" dd@,|?" dd@   " @ ` n?" dd@   @@``PR    @ ` ` p>> }u (  +  6@V P  yFuture Role of Large Neutral Amino Acids in the Transport of Phenylalanine into the BrainClick to edit Master title stylez z  0Z   RClick to edit Master text styles Second level Third level Fourth level Fifth level!     S  0 ``  X*  0H `   Z*  0 `   Z*H  0޽h ? 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