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Beloborodova N.V.,Negovsky Research Institute of General Reanimatology | Moroz V.V.,Negovsky Research Institute of General Reanimatology | Osipov A.A.,Negovsky Research Institute of General Reanimatology | Bedova A.Y.,Negovsky Research Institute of General Reanimatology | And 3 more authors.
Biochemistry (Moscow) | Year: 2015

Previous studies showed that large amounts of phenylcarboxylic acids (PhCAs) are accumulated in a septic patient's blood due to increased endogenous and microbial phenylalanine and tyrosine biotransformation. Frequently, biochemical aromatic amino acid transformation into PhCAs is considered functionally insignificant for people without monogenetic hereditary diseases. The blood of healthy people contains the same PhCAs that are typical for septic patients as shown in this paper. The overall serum PhCAs level was 6 μM on average as measured by gas chromatography with flame ionization detection. This level is a stable biochemical parameter indicating the normal metabolism of aromatic amino acids. The concentrations of PhCAs in the metabolic profile of healthy people are distributed as follows: phenylacetic ≈ p-hydroxyphenyllactic > p-hydroxyphenylacetic > phenyllactic ≈ phenylpropionic > benzoic. We conclude that maintaining of stable PhCAs level in the serum is provided as the result of integration of human endogenous metabolic pathways and microbiota. © 2015 Pleiades Publishing, Ltd. Source

Fedotcheva N.I.,Russian Academy of Sciences | Litvinova E.G.,Russian Academy of Sciences | Osipov A.A.,Negovsky Research Institute of General Reanimatology | Olenin A.Y.,Moscow State University | And 2 more authors.
Biophysics (Russian Federation) | Year: 2015

The effects of microbial phenolic metabolites on the activities of enzymes of the tricarboxylic acid cycle were investigated in isolated mitochondria. The detection of metabolites of the tricarboxylic acid cycle in the blood of patients with sepsis as potential biomarkers of mitochondrial dysfunction was investigated. We found that microbial phenolic metabolites possess an inhibitory effect on the activity of dehydrogenases, as determined by the reduction of dichlorophenolindophenol and nitroblue tetrazolium in liver mitochondria and liver homogenates. The effect was more pronounced in the case of the oxidation of NAD-dependent substrates than succinate oxidation, as well as at lower concentrations of microbial metabolites than in the case of inhibition of respiration. Using gas chromatography coupled with mass spectrometry it was shown that the content of the tricarboxylic acid cycle metabolites is lower in the blood of patients with sepsis as compared to healthy donors. Our data demonstrate that microbial phenolic acids can significantly contribute to mitochondrial dysfunction and to metabolic suppression, both of which are characteristic of these pathologies. © 2015, Pleiades Publishing, Inc. Source

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