Tandemly repeated sequences in mtDNA control region of whitefish, Coregonus lavaretus.

Length variation of the mitochondrial DNA control region was observed with PCR amplification of a sample of 138 whitefish (Coregonus lavaretus). Nucleotide sequences of representative PCR products showed that the variation was due to the presence of an approximately 100-bp motif tandemly repeated two, three, or five times in the region between the conserved sequence block-3 (CSB-3) and the gene for phenylalanine tRNA. This is the first report on the tandem array composed of long repeat units in mitochondrial DNA of salmonids.     

A 5-methyltryptophan resistant rice mutant,MTR1, selected in tissue culture

Summary Cell lines resistant to tryptophan analogue 5-methyltryptophan (5MT) were selected in seed-derived calli of Oryza sativa L. var. Norin 8. Plants were regenerated (R₁ from one selected callus line (MTR1). In three out of the six R₁ plants, 5MT resistance was inherited in the R₂ and R₃ generations as a dominant nuclear mutation. Segregation ratios in the progeny of heterozygous plants were 11. Morphological and fertility variation seen in some of the R₂ plants were not correlated with 5-methyltryptophan resistance. Resistance in the MTR1 callus was due to the accumulation of high levels of free tryptophan (87-fold) that was associated with an increase in free phenylalanine content (9-fold). The leaves of resistant plants also contained elevated levels of free tryptophan and phenylalanine.Abbreviations 2,4-D 2,4-dichlorophenoxyacetic acid - MS Murashige and Skoog (1962) basal medium - 5MT D,L-5-methyltryptophan - phe phenylalanine - trp tryptophan - tyr tyrosine     

Effect of orally administered phenylalanine with and without glucose on insulin, glucagon and glucose concentrations.

OBJECTIVE: As part of our studies of the metabolic effects of ingested proteins, we are currently investigating the effects of ingestion of individual amino acids. The objective of the present study was to determine whether ingested phenylalanine stimulates insulin and/or glucagon secretion, and if phenylalanine ingested with glucose modifies the insulin, glucagon or glucose response to the ingested glucose. DESIGN: Six healthy subjects were tested on 4 separate occasions. Plasma phenylalanine, glucose, insulin, glucagon, and total alpha amino nitrogen (AAN) (i.e., total amino acids) concentrations were measured at various times during a 2.5 h period after ingestion of 1 mmol phenylalanine/kg lean body mass, 25 g glucose, 1 mmol phenylalanine/kg lean body mass+25 g glucose, or water only, given in random order. RESULTS: Following phenylalanine ingestion, the circulating phenylalanine concentration increased approximately 14 fold and remained elevated for the duration of the experiment. Glucagon and AAN increased, insulin increased modestly, and glucose was unchanged when compared to water ingestion. When glucose was ingested with phenylalanine, the circulating phenylalanine, glucagon, AAN, and insulin area responses were approximately the sum of the responses to phenylalanine alone and glucose alone. However, the plasma glucose area response was decreased 66% when phenylalanine was co-ingested with glucose. CONCLUSION: In summary, phenylalanine in an amount moderately greater than that in a large protein meal stimulates an increase in insulin and glucagon concentration. It markedly attenuates the glucose-induced rise in plasma glucose when ingested with glucose.     

Variation in the free amino acid content of skeletal muscle of Ophicephalus punctatus (Bloch)

The skeletal muscle of Ophicephalus punctatus contains nine essential free amino acids, arginine, histidine, isoleucine, leucine, methionine, phenylalanine, threonine, valine and lysine, and eight non-essential amino acids, alanine, aspartic acid, cystine, glutamic acid, glycine, tyrosine, proline and serine. Histidine and lysine dominated the free amino acids pool. Seasonal variation was detected in the levels of histidine, arginine, leucine, phenylalanine, glycine, cystine and serine with highest values occurring in April and again in November. Changes were also detected in the concentrations of certain amino acids as the fish grew in size. Levels of free amino acids did not significantly differ between sexes. Factors effecting variation are discussed.     

Use of 13C in biosynthetic studies. The labelling pattern in tenellin enriched from isotope-labelled acetate, methionine, and phenylalanine

The biogenetic origin of the carbon atoms in tenellin has been established by adding 13C-enriched compounds to cultures of Beauveria bassiana, and determining the isotopic distribution in the metabolite by 13C nuclear magnetic resonance spectrometry. Tenellin is formed by condensation of an acetate-derived polyketide chain with a phenylpropanoid unit that may be phenylalanine. Alternate carbon atoms of the polyketide chain were labelled with sodium [1(-13C)]- and [2-(13C]-acetate; sodium [1,2-(13C)]acetate was incorporated as intact two-carbon units, the presence of which in tenellin was apparent from coupling between adjacent 13C-enriched carbons. Substituent methyl groups of the polyketide-derived alkenyl chain were labelled with L-[Me-13C]methionine. The labelling patterns from DL-[carboxy-13C]phenylalanine and DL-[alpha-13C]phenylalanine indicated a rearrangement of the propanoid component at some stage in the synthesis. The mass spectrum of tenellin from cultures administered L-[15N]phenylalanine showed isotopic enrichment similar to that obtained with 13C- or 14C-labelled phenylalanine. During incorporation of L-[carboxy-14C, beta-3H]phenylalanine 96% of the tritium label was lost, discounting the possibility of a 1,2-hydride shift during biosynthesis of the metabolite.     

Compartmentation of phenylacetic and cinnamic acid synthesis in spinach

Applying labelled phenylalanine or tyrosine to purified intact spinach chloroplasts, only the corresponding phenylacetic acids but not the cinnamic acids could be detected. The addition of mercaptoethanol or dl -dithiothreitol and the variation of light conditions had only a slight effect. However, cinnamic acids could be found together with phenylacetic acids in leaf homogenates indicating the presence of phenylalanine and/or tyrosine ammonia lyase outside the spinach chloroplasts. Similar results were obtained with barley leaf homogenates, where cinnamic acids were the main products. Reviewing recent findings on amino acid synthesis in spinach leaves, it may be concluded that the synthesis of aromatic amino acids is restricted to the chloroplast, whereas the metabolism of secondary aromatic compounds is predominantly localized outside the chloroplasts.     

Changes in plasma phenylalanine, isoleucine, leucine, and valine are associated with significant changes in intracranial pressure and jugular venous oxygen saturation in patients with severe traumatic brain injury

Changes in plasma aromatic amino acids (AAA?=?phenylalanine, tryptophan, tyrosine) and branched chain amino acids (BCAA?=?isoleucine, leucine, valine) levels possibly influencing intracranial pressure (ICP) and cerebral oxygen consumption (SjvO(2)) were investigated in 19 sedated patients up to 14?days following severe traumatic brain injury (TBI). Compared to 44 healthy volunteers, jugular venous plasma BCAA were significantly decreased by 35% (p?相似文献   

Purification, characterization and identification of rat liver histidine-pyruvate aminotransferase isoenzymes.

1. Histidine-pyruvate aminotransferase (isoenzyme 1) was purified to homogeneity from the mitochondrial and supernatant fractions of rat liver, as judged by polyacrylamide-gel electrophoresis and isolectric focusing. Both enzyme preparations were remarkably similar in physical and enzymic properties. Isoenzyme 1 had pI8.0 and a pH optimum of 9.0. The enzyme was active with pyruvate as amino acceptor but not with 2-oxoglutarate, and utilized various aromatic amino acids as amino donors in the following order of activity: phenylalanine greater than tyrosine greater than histidine. Very little activity was found with tryptophan and 5-hydroxytryptophan. The apparent Km values were about 2.6mM for histidine and 2.7 mM for phenylalanine. Km values for pyruvate were about 5.2mM with phenylalanine as amino donor and 1.1mM with histidine. The aminotransferase activity of the enzyme towards phenylalanine was inhibited by the addition of histidine. The mol.wt. determined by gel filtration and sucrose-density-gradient centrifugation was approx. 70000. The mitochondrial and supernatant isoenzyme 1 activities increased approximately 25-fold and 3.2-fold respectively in rats repeatedly injected with glucagon for 2 days. 2. An additional histidine-pyruvate aminotransferase (isoenzyme 2) was partially purified from both the mitochondrial and supernatant fractions of rat liver. Nearly identical properties were observed with both preparations. Isoenzyme 2 had pI5.2 and a pH optimum of 9.3. The enzyme was specific for pyruvate and did not function with 2-oxoglutarate. The order of effectiveness of amino donors was tyrosine = phenylalanine greater than histidine greater than tryptophan greater than 5-hydroxytryptophan. The apparent Km values for histidine and phenylalanine were about 0.51 and 1.8 mM respectively. Km values for pyruvate were about 3.5mM with phenylalanine and 4.7mM with histidine as amino donors. Histidine inhibited phenylalanine aminotransferase activity of the enzyme. Gel filtration and sucrose-density-gradient centrifugation yielded a mol.wt. of approx. 90000. Neither the mitochondrial nor the supernatant isoenzyme 2 activity was elevated by glucagon injection.     

Simultaneous determination of tyrosine, phenylalanine and deoxyguanosine oxidation products by liquid chromatography-tandem mass spectrometry as non-invasive biomarkers for oxidative damage

We developed an isotope dilution HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry (HPLC-APCI-MS/MS) method for the simultaneous determination of p-tyrosine, phenylalanine, o,o'-dityrosine, m-tyrosine, o-tyrosine, 3-chlorotyrosine and 3-nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OHdG) that requires no extensive sample pre-treatment. p-[(2)H(4)]Tyrosine and o,o'-[(2)H(6)]dityrosine were used as internal standards. Calibration curves of the method were linear (r(2)=0.990-0.999) over a concentration range of 0.03-10 microM for o-tyrosine; 0.04-10 microM for 3-nitrotyrosine and 3-chlorotyrosine; 0.05-10 microM for o,o'-dityrosine; and for m-tyrosine; 1.0-100 microM for p-tyrosine and for phenylalanine; and 0.01-10 microM for 8-OHdG. The detection limits were from 0.025 to 0.05 microM for the tyrosine derivatives; 0.01 microM for 8-OHdG; and 0.5 microM for p-tyrosine and for phenylalanine, respectively. Within-day coefficients of variation (CV) for spiked human urine samples ranged from 2.7 to 7.0%, except for 8-OHdG (13.7%). Between-day variations ranged from 7.9 to 13.0%, except for o-tyrosine (CV = 18.2%), and for 8-OHdG (CV = 24.7%).The background levels of p-tyrosine, phenylalanine, o,o'-dityrosine, and o-tyrosine in morning urine of eight healthy volunteers were 3890+/-590, 3420+/-730, 5.8+/-0.3, and 9.2+/-1.5 micromol/mol creatinine, respectively. Using the present HPLC-APCI-MS/MS method, the urinary background levels of m-tyrosine, 3-chlorotyrosine, 3-nitrotyrosine and 8-OHdG were below the limit of detection.     

Rapid automated ion-exchange analysis of plasma tyrosine and phenylalanine with data print-out

A rapid automated method with data print-out is described for quantitation of plasma phenylalanine and tyrosine from 0.100 ml of sample. The system uses the Rank-Hilger Chromaspek amino acid analyser linked to a Digico M16E computer.Amino acid concentrations up to 3000 μM can be quantitated without repeat dilutions and assessment of precision at the 500 μM level, produced coefficients of variation of 2.2% for tyrosine and 2.5% for phenylalanine. Recovery determinations from a plasma pool gave a mean recovery of 99.4% for tyrosine and 99.7% for phenylalanine.Correlation with established fluorimetric techniques was excellent (r = 0.986 for tyrosine, r = 0.976 for phenylalanine). By using the same resin column for both the rapid separation of tyrosine and phenylalanine, and the standard physiological fluid separation, full analysis capability is retained with easy interchange between the two systems.     

Evidence for two aromatic amino acid-binding sites, one ATP-dependent and the other ATP-independent, in the Escherichia coli regulatory protein TyrR

In Escherichia coli , genetic regulation of aromatic amino acid biosynthesis and uptake is effected by the protein TyrR, which acts via ligand-mediated repression and activation. Characterization of the interactions of tyrosine, phenylalanine and tryptophan with TyrR revealed the presence of two separate aromatic amino acid-binding sites, one ATP-dependent, the other ATP-independent. Binding to the ATP-dependent site induces the self-association of TyrR. Using sedimentation equilibrium analyses, dissociation constants for this site in the dimeric and hexameric forms of TyrR were determined to be 330 μM and 24 μM, respectively, for tyrosine, and 55 mM and 3.7 mM, respectively, for phenylalanine. Tryptophan bound with a strength similar to that of phenylalanine, and both phenylalanine and tryptophan competed with the binding of tyrosine. The ATP-independent site, which has not been observed previously, was characterized by ultraviolet (u.v.) difference spectroscopy and a sedimentation-velocity meniscus-depletion method. Phenylalanine bound co-operatively to this site, exhibiting half-saturation at 260 µM. Tryptophan competed weakly with phenylalanine, half-saturation occurring at 1.2 mM. No binding of tyrosine to this site could be detected. We propose that the binding of phenylalanine or tryptophan to this ATP-independent site is responsible for phenylalanine- and tryptophan-mediated regulation by TyrR.     

Isolation and sequence of a cDNA clone which contains the complete coding region of rat phenylalanine hydroxylase. Structural homology with tyrosine hydroxylase, glucocorticoid regulation, and use of alternate polyadenylation sites

Screening of a rat liver cDNA expression library constructed in the vector lambda gt11 with an affinity purified antiserum to rat phenylalanine hydroxylase has resulted in the isolation of two clones which contain the complete coding region (1362 base pairs) of phenylalanine hydroxylase and the entire 3'-untranslated region (562 base pairs). From the nucleotide sequence we deduced the amino acid sequence of the enzyme. The molecular weight is 51,632 (452 amino acids). The rat enzyme is highly homologous to human phenylalanine hydroxylase. The two proteins differ in only 36 amino acids (92% homology), many of which are conservative changes. A dot matrix computer program was used to analyze regions of homology with the amino acid sequence of rat tyrosine hydroxylase. Considerable homology was detected from amino acid 140 in the rat enzyme to the C terminus, but little or no homology was apparent in the N-terminal region. The cDNA clone was used to determine the levels of phenylalanine hydroxylase mRNA in rat tissues using RNA blot hybridization. Two mRNA species were detected, with approximate lengths of 2,000 and 2,400 nucleotides, which appear to derive from use of alternate polyadenylation signals. No difference in mRNA size was found in rats which have different phenylalanine hydroxylase alleles. The kidney was found to contain about 10% of the mRNA found in the liver, and no phenylalanine hydroxylase mRNA was detected in rat brain. Reuber H4 hepatoma cells were also analyzed for phenylalanine hydroxylase mRNA. The parental cells contained mRNA species of the same sizes as in rat liver. Incubation in 10(-6) M hydrocortisone for 24 h resulted in an 18-fold increase in the mRNA level. Mutant hepatoma cells which express very little phenylalanine hydroxylase contained less than 5% of the parental mRNA, but the gene still responded to hydrocortisone.     

In vivo regulation of phenylalanine hydroxylation to tyrosine, studied using enrichment in apoB-100

Phenylalanine hydroxylation is necessary for the conversion of phenylalanine to tyrosine and disposal of excess phenylalanine. Studies of in vivo regulation of phenylalanine hydroxylation suffer from the lack of a method to determine intrahepatocyte enrichment of phenylalanine and tyrosine. apoB-100, a hepatic export protein, is synthesized from intrahepatocyte amino acids. We designed an in vivo multi-isotope study, [(15)N]phenylalanine and [2H2]tyrosine to determine rates of phenylalanine hydroxylation from plasma enrichments in free amino acids and apoB-100. For independent verification of apoB-100 as a reflection of enrichment in the intrahepatocyte pool, [1-(13)C]lysine was used as an indicator amino acid (IAA) to measure in vivo changes in protein synthesis in response to tyrosine supplementation. Adult men (n = 6) were fed an amino acid-based diet with low phenylalanine (9 mg.kg(-1).day(-1), 4.54 mumol.kg(-1).,h(-1)) and seven graded intakes of tyrosine from 2.5 (deficient) to 12.5 (excess) mg.kg(-1).day(-1). Gas chromatography-quadrupole mass spectrometry did not detect any tracer in apoB-100 tyrosine. A new and more sensitive method to measure label enrichment in proteins using isotope ratio mass spectrometry demonstrated that phenylalanine hydroxylation measured in apoB-100 decreased linearly in response to increasing tyrosine intake and reached a break point at 6.8 mg.kg(-1).day(-1). IAA oxidation decreased with increased tyrosine intake and reached a break point at 6.0 mg.kg(-1).day(-1). We conclude: apoB-100 is an accurate and useful measure of changes in phenylalanine hydroxylation; the synthesis of tyrosine via phenylalanine hydroxylation is regulated to meet the needs for protein synthesis; and that plasma phenylalanine does not reflect changes in protein synthesis.     

Eliminating tyrosine sequence variants in CHO cell lines producing recombinant monoclonal antibodies

Amino acid sequence variants are defined as unintended amino acid sequence changes that contribute to product variation with potential impact to product safety, immunogenicity, and efficacy. Therefore, it is important to understand the propensity for sequence variant (SV) formation during the production of recombinant proteins for therapeutic use. During the development of clinical therapeutic products, several monoclonal antibodies (mAbs) produced from Chinese Hamster Ovary (CHO) cells exhibited SVs at low levels (≤3%) in multiple locations throughout the mAbs. In these examples, the cell culture process depleted tyrosine, and the tyrosine residues in the recombinant mAbs were replaced with phenylalanine or histidine. In this work, it is demonstrated that tyrosine supplementation eliminated the tyrosine SVs, while early tyrosine starvation significantly increased the SV level in all mAbs tested. Additionally, it was determined that phenylalanine is the amino acid preferentially misincorporated in the absence of tyrosine over histidine, with no other amino acid misincorporated in the absence of tyrosine, phenylalanine, and histidine. The data support that the tyrosine SVs are due to mistranslation and not DNA mutation, most likely due to tRNA^Tyr mischarging due to the structural similarities between tyrosine and phenylalanine. Biotechnol. Bioeng. 2013; 110: 1087–1097. © 2012 Wiley Periodicals, Inc.     

Effects of adrenergic agents, vasopressin and ionophore A23187, on the phosphorylation of, and flux through, phenylalanine hydroxylase in rat liver cells.

The adrenergic amines noradrenaline and adrenaline increased flux through phenylalanine hydroxylase by approx. 50%. This effect, which appears to be mediated by an alpha-adrenergic mechanism, was accompanied by a rapid increase in the phosphorylation of phenylalanine hydroxylase. Although ionophore A23187 mimicked the effects of the adrenergic amines, vasopressin was completely without effect on either phenylalanine hydroxylation or enzyme phosphorylation. Flux through phenylalanine hydroxylase in young rats (80 g) was insensitive to alpha-adrenergic, but sensitive to beta-adrenergic, agents. Consistent with previous observations [Fisher & Pogson (1984) Biochem. J. 219, 79-85] the present data indicate a close correlation between phosphorylation state and flux rate (i.e. enzyme activity).     

Dietary supplements of mixtures of indispensable amino acids lacking threonine, phenylalanine or histidine increase the activity of hepatic threonine dehydrogenase, phenylalanine hydroxylase or histidase, respectively, and prevent growth depressions in chicks caused by dietary excesses of threonine, phenylalanine, or histidine*

Experiments were carried out to determine whether the addition of a mixture of indispensable amino acids (IAA) lacking in threonine, phenylalanine or histidine, respectively, to a nutritionally complete diet would increase the hepatic activities of the rate-limiting enzymes for catabolism of threonine, phenylalanine or histidine and prevent the adverse effects of the amino acid on growth when the dietary level of the amino acid is excessive. Week old Leghorn chicks were fed semi-purified diets containing 19% crude protein to which were added no IAA supplement or 10% crude protein from an IAA mix and 5 graded levels of either L-threonine, L-phenylalanine or L-histidine in a 2 x 5 factorial arrangement of treatments. Each amino acid was investigated in a separate experiment involving four replicate pens (seven chicks each) per diet. Weight gains and feed consumptions were determined on the fourteenth day of each experiment. The groups receiving no excess, and 1.0% or 2.0% excesses of amino acids were sampled on the fifteenth day for enzyme activities and plasma amino acid concentrations. Weight gain and/or feed consumption were lower, and plasma concentrations of threonine, phenylalanine and histidine were higher, in chicks receiving 1.5 to 2.0% dietary additions of threonine, phenylalanine, and histidine, respectively, than in chicks that did not receive these amino acids. Chicks that received the amino acids in diets that also contained the IAA supplement had better growth and feed consumption, lower plasma concentrations of threonine, phenylalanine or histidine, higher plasma concentrations of other indispensable amino acids, and higher activities of threonine dehydrogenase, phenylalanine hydroxylase, and histidase than chicks receiving excess amino acids in the absence of IAA supplements. We conclude that the dietary level of protein, not the dietary level of individual amino acids, is the primary determinant of the activity of amino acid degrading enzymes in liver. The increased activity of these enzymes may be the mechanism by which dietary protein alleviates the adverse effects of excessive levels of individual amino acids.     

AMINO ACIDS AND CEREBRAL EXCITABILITY1

Abstract— —Seizure threshold, measured with hexafluorodiethyl ether, was shown to be reduced in immature albino rats fed a diet containing excess tryptophan. Similar diets containing excess glycine, serine, leucine, valine or lysine had no effect on seizure threshold. Previous studies had shown phenylalanine, tyrosine and methionine to enhance cerebral excitability with the same technique. The increased cerebral excitability was shown to occur within 24 hr following diet supplementation with phenylalanine. Brain concentration of hexafluorodiethyl ether was identical in control and experimental animals, although the experimental animals had lowered seizure thresholds; this established an alteration in cerebral excitability rather than variation in tissue penetration by the convulsant. Alterations were found in blood and brain ammonia in serine, lysine and methionine supplemented animals. Brain glutamate and glutamine were lowered in methionine-supplemented animals; however, it was concluded that this effect was not causally related to the increased cerebral excitability.     

Separation of phenylalanine transport events by using selective inhibitors, and identification of a specific uncoupler activity in Yersinia pestis.

Phenylalanine transport in Yersinia pestis TJW was differentially inhibited by sulfhydryl blocking reagents, uncoupling agents, and respiratory inhibitors. Kinetic studies with potassium cyanide and sodium azide showed that these compounds have no immediate effect on the initial rate of phenylalanine transport, but have an immediate and severe inhibitory effect on the rate of oxygen uptake. Identical studies with p-chloromercuribenzoate (pCMB) and 2,4-dinitrophenol (DNP) showed that these compounds have an instantaneous and total inhibitory effect on phenylalanine transport. DNP stimulated oxygen uptake, and pCMB caused only a sluggish inhibiton of oxygen uptake. pCMB acted as a competitive inhibitor of phenylalanine transport, whereas DNP inhibitied noncompetitively. Arrenius plots of the initial rate of phenylalanine transport in pCMB- and DNP-treated cells showed that DNP alters the transition temperature of the phenylalanine transport system from 17 C for control cells to 12 C. DNP did not inhibit transport when cells were treated at temperatures of 2 to 10 C. PCMB did not alter the normal transition temperature and inhibited phenylalanine transport over a 2 to 30 C temperature range. Efflux induced by both pCMB and DNP were blocked by placing cells at low temperatures (2 to 20 C). Inhibition of adenosine 5'-triphosphate synthesis by DNP did not show any temperature sensitivity as did phenylalanine transport. These data indicate that: (i) respiration is not obligatory for active transport of phenylalanine in Y. pestis TJW; and (ii) pCMB inhibits transport activity by reacting with the sulfhydryl group(s) at the carrier binding site. The data show that the uncoupler, DNP, selectively alters a temperature-dependent property of phenylalanine transport, that is not related to uncoupling activity of DNP , and probably involves membrane lipid alterations.     

Gene Structure, Chromosomal Location, and Expression Pattern of Maleylacetoacetate Isomerase

The gene for maleylacetoacetate isomerase (MAAI) (EC 5.2.1.2) was the last gene in the mammalian phenylalanine/tyrosine catabolic pathway to be cloned. We have isolated the human and murine genes and determined their genomic structure. The human gene spans a genomic region of approximately 10 kb, has 9 exons ranging from 50 to 528 bp in size, and was mapped to 14q24.3-14q31.1 using fluorescence in situ hybridization. The complete catabolic pathway of phenylalanine/tyrosine is normally restricted to liver and kidney, but the maleylacetoacetate isomerase gene is expressed ubiquitously. This suggests a possible second role for the MAAI protein different from phenylalanine/tyrosine catabolism. We have searched for mutations in the maleylacetoacetate isomerase gene in four cases of unexplained severe liver failure in infancy with clinical similarities to hereditary tyrosinemia type I (pseudotyrosinemia). Several amino acid changes were identified, but all were found to retain MAAI activity and thus represent protein polymorphisms. We conclude that MAAI deficiency is not a common cause of the pseudotyrosinemic phenotype.