Article ; Online: Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.
Metabolomics : Official journal of the Metabolomic Society
2024 Volume 20, Issue 2, Page(s) 36
Abstract: Introduction: Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying ... ...
| Abstract | Introduction: Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging. Objective: To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality. Methods: We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact. Results: Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased. Conclusion: Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction. |
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| MeSH term(s) | Humans ; Amino Acids ; Shock, Septic ; N-Formylmethionine ; Metabolomics ; Sepsis ; Methionine ; Lactic Acid ; Racemethionine ; Mitochondrial Diseases |
| Chemical Substances | Amino Acids ; N-Formylmethionine (4289-98-9) ; Methionine (AE28F7PNPL) ; Lactic Acid (33X04XA5AT) ; Racemethionine (73JWT2K6T3) |
| Language | English |
| Publishing date | 2024-03-06 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 2250617-2 |
| ISSN | 1573-3890 ; 1573-3882 |
| ISSN (online) | 1573-3890 |
| ISSN | 1573-3882 |
| DOI | 10.1007/s11306-024-02089-z |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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