Plasma concentrations of phenyllactic acid in phenylketonuria

Clemens, P.; Schünemann, Martin H.; Hoffmann, Georg F.; Kohlschütter, Alfried

doi:10.1007/bf01799690

Cited by 9 publications

(6 citation statements)

References 3 publications

(2 reference statements)

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“…Our established LC-MS measurement method does not discriminate between L-PLA and D-PLA. Blood levels of L-PLA in the μM range are only found in patients with phenylketonuria [39]. L-PLA is 35-fold less potent than D-PLA at HCA 3 (Table 3) and plasma samples from basal conditions (0.4 μM) were sufficient to inhibit forskolin-induced cAMP formation via HCA 3 (S5 Table), potentially due to presence of D-PLA derived from alimentary microbiota sources.…”

Section: Resultsmentioning

confidence: 99%

Metabolites of lactic acid bacteria present in fermented foods are highly potent agonists of human hydroxycarboxylic acid receptor 3

et al. 2019

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The interplay of microbiota and the human host is physiologically crucial in health and diseases. The beneficial effects of lactic acid bacteria (LAB), permanently colonizing the human intestine or transiently obtained from food, have been extensively reported. However, the molecular understanding of how LAB modulate human physiology is still limited. G protein-coupled receptors for hydroxycarboxylic acids ( HCAR ) are regulators of immune functions and energy homeostasis under changing metabolic and dietary conditions. Most mammals have two HCAR (HCA 1 , HCA 2 ) but humans and other hominids contain a third member (HCA 3 ) in their genomes. A plausible hypothesis why HCA 3 function was advantageous in hominid evolution was lacking. Here, we used a combination of evolutionary, analytical and functional methods to unravel the role of HCA 3 in vitro and in vivo . The functional studies included different pharmacological assays, analyses of human monocytes and pharmacokinetic measurements in human. We report the discovery of the interaction of D-phenyllactic acid (D-PLA) and the human host through highly potent activation of HCA 3 . D-PLA is an anti-bacterial metabolite found in high concentrations in LAB-fermented food such as Sauerkraut. We demonstrate that D-PLA from such alimentary sources is well absorbed from the human gut leading to high plasma and urine levels and triggers pertussis toxin-sensitive migration of primary human monocytes in an HCA 3 -dependent manner. We provide evolutionary, analytical and functional evidence supporting the hypothesis that HCA 3 was consolidated in hominids as a new signaling system for LAB-derived metabolites.

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Section: Resultsmentioning

confidence: 99%

Metabolites of lactic acid bacteria present in fermented foods are highly potent agonists of human hydroxycarboxylic acid receptor 3

et al. 2019

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“…Blau et al, 1973;Olek et al, 1974;Langenbeck et al, 1978a) has finally been superseded by DNA analysis (Giittler and Woo, 1986). The measurement of phe metabolites also does not substantially improve monitoring of dietary therapy (Kaufman, 1989), although urinary PPA or PLA levels at given plasma phe levels, because of slow transaminase induction (see above), may differentiate between acute and chronic derangements of dietary control (Langenbeck et aI., 1978a;Clemens et al, 1990a). However, the transamination capacity at full induction may be one of the long-sought indicators for the degrees of reversible and irreversible effects of hyperphenylalaninaemia or their absence (Primrose, 1983), and this is best measured with the metabolites in blood and secondarily also in urine.…”

Section: Discussionmentioning

confidence: 99%

A synopsis of the unconjugated acidic transamination metabolites of phenylalanine in phenylketonuria

Langenbeck

Behbehani

Mench-Hoinowski

1991

J of Inher Metab Disea

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We present blood and urine levels of unconjugated o-hydroxyphenylacetic, phenyllactic and phenylpyruvic acids in 61 children (2 years of age and above) and juveniles with phenylketonuria on or partially off diet. The samples were obtained during 185 scheduled outpatient visits and have been analysed with gas chromatographic methods. The compiled data define reference ranges of phenylalanine transamination capacity and of renal transport of metabolites which may be of value in further studies on the pathogenesis of phenylketonuria.

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“…Moreover, brain PLA levels are considerable higher for phenylketonuria mouse model. These findings could be and indicator of potential acute neurotoxicity of PLA in PKU patients [6,7].…”

Section: Introductionmentioning

confidence: 79%

A Biochemical Method for Tyrosine Determination in Phenylketonuria Using a Colorimetric Enzymatic Approach

Mocanu¹,

Bocec²,

Gradinaru³

et al. 2020

Rev. Chim.

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Phenylketonuria is a serious genetic disease caused by a deficiency of phenylalanine metabolism, an essential amino acid found in daily nutrition. This disorder is caused by the lack of a specific enzyme called phenylalanine hydroxylase which mediates the conversion of phenylalanine to tyrosine). Thus, after ingestion of phenyl alanine-rich proteins, the amino acid concentration increases considerably in the blood due to proteolysis. Genetic deffects of enzymes responsible for phenylalanine metabolic conversion were intensively studied. Among them the defect of gene encoding phenylalanine hydroxylase has a higher notoriety. This genetic defect is translated in an inactive enzyme constructs that impair the aminoacid hydroxylation. This physiological stage is also called hyperphenylalaninemia where slightly high levels of phenylalanine are noticed in the blood or urine. Consequently, the amino acid is converted to phenylpyruvic acid by transamination, the later displaying a particularly toxic effect against brain tissues. The aim of this study was to quantify tyrosine in the blood of patients suffering of phenylketonuria by an alternative enzymatic method. The tyrosinase used in this assay was extracted from commercial mushrooms (Agaricus bisporus) following the Haghbeen protocol with some modifications. Two chromatographic steps (molecular exclusion chromatography and ionic exchange chromatography) were used during the enzyme purification process. High purity samples were concentrated using ultrafiltration. The tyrosinase was screened by a classical enzymatic microplate assay having DOPA as a substrate. Finally the pure enzyme was used in order to quantify tyrosine from different standard solutions. The level of tyrosine from deproteinized serum samples was determined using a similar enzymatic strategy.

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Plasma concentrations of phenyllactic acid in phenylketonuria

Cited by 9 publications

References 3 publications

Metabolites of lactic acid bacteria present in fermented foods are highly potent agonists of human hydroxycarboxylic acid receptor 3

Metabolites of lactic acid bacteria present in fermented foods are highly potent agonists of human hydroxycarboxylic acid receptor 3

A synopsis of the unconjugated acidic transamination metabolites of phenylalanine in phenylketonuria

A Biochemical Method for Tyrosine Determination in Phenylketonuria Using a Colorimetric Enzymatic Approach

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