Biology subjects

Hoffmann, V.

Publications and source records attributed to Hoffmann, V..

3 recordsLinked to original sources

bioRxiv2026

Divergent specificity of PatA, GabT, and IlvE defines the branched transamination of Nε-carboxymethyllysine and its metabolite Nε-carboxymethylcadaverine in Escherichia coli

Thermal food processing generates N{varepsilon}-carboxymethyllysine (CML), a key advanced glycation end product (AGE) and marker of the Maillard reaction in food. Escherichia coli utilizes CML as a nitrogen source. While SpeC initiates degradation by decarboxylating CML to N-carboxymethylcadaverine (CM-Cad), the enzymes liberating the nitrogen remained unknown. Here, we identify PatA, GabT, and IlvE as the glutamate-dependent transaminases responsible for CML and CM-Cad transamination. Our results reveal a branched metabolic network rather than a linear pathway: PatA shows specificity towards both substrates, while GabT and IlvE selectively process CM-Cad and CML, respectively. We further demonstrate that the carboxymethyl piperideinium ion (CM-Pip) is formed spontaneously following CM-Cad transamination and reveal the previously unknown carboxymethyl-tetrahydropicolinic acid (CM-THPA) as novel metabolite in CML metabolism. Combining molecular microbiology, biochemistry, and analytical chemistry, we demonstrate that these transaminases are essential for integrating dietary CML into bacterial nitrogen metabolism, providing a model for microbial AGE processing via underground metabolism.

microbiology↗

bioRxiv2023

ADP-ribose-acceptor hydrolase 2 (Arh2) deficiency results in cardiac dysfunction, tumorigenesis, inflammation, and decreased survival

ADP-ribosylation is a reversible reaction with ADP-ribosyltransferases catalyzing the forward reaction and ADP-ribose-acceptor hydrolases (ARHs) hydrolyzing the ADP-ribose acceptor bond. ARH2 is a member of the 39-kDa ARH family (ARH1-3), which is expressed in heart and skeletal muscle. ARH2 failed to exhibit any in vitro enzymatic activity. To determine its possible in vivo activities, Arh2-knockout (KO) and - heterozygous (Het) mice were generated using CRISPR-Cas9. Arh2-KO mice exhibited decreased cardiac contractility by MRI, echocardiography and dobutamine stress with cardiomegaly and abnormal motor function. Arh2-Het mice showed results similar to those seen in Arh2-KO mice except for cardiomegaly. Arh2-KO and -Het mice and mouse embryonic fibroblasts (MEFs) developed spontaneous tumors and subcutaneous tumors in nude mice. We identified 13 mutations in Arh2-Het MEFs and heterozygous tumors, corresponding to human ARH2 mutations in cancers obtained from COSMIC. Of interest, the L116R mutation in Arh2 gene plays a critical role in aggressive tumorigenesis in nude mice, corresponding to human ARH2 mutations in stomach adenocarcinoma. Both genders of Arh2-KO and -Het mice showed increased unexpectedly deaths and decreased survival rate during a 24-month observation, caused by tumor, inflammation, non-inflammation (e.g., cardiomegaly, dental dysplasia), and congenital diseases. Thus, Arh2 plays a pivotal role in cardiac function, tumorigenesis, inflammation, and overall survival.

cancer biology↗

bioRxiv2020

Molecular classification of the placebo effect in nausea

Numerous studies have shown that the mere expectation improvement can alleviate symptoms in various conditions. These placebo effects often include reliable changes in central and peripheral organ systems. Here, we tested for the first time whether placebo effects can be monitored and predicted by plasma proteins. In a randomized controlled design, 90 healthy participants were exposed to a 20-min vection stimulus on two separate days and were randomly allocated to placebo treatment or no treatment on the second day. Significant placebo effects on nausea, motion sickness, and gastric activity could be verified. Using state-of-the-art proteomics, 74 differentially regulated proteins were identified in placebo-treated participants as compared to no-treatment controls. Gene ontology (GO) enrichment analyses of these proteins revealed acute-phase proteins as well as microinflammatory proteins to be reliable plasma correlates of the placebo effect. Regression analyses showed that day-adjusted scores of nausea indices in the placebo group were predictable by the identified GO protein signatures. We next identified specific plasma proteins, for which a significant amount of variance could be explained by the experimental factors sex, group, nausea, or their interactions. GO enrichment analyses of these proteins identified grooming behavior as a prominent hit, based on neurexin-1 (NRXN1) and contactin-associated protein-like 4 (CNTNAP4). Finally, Receiver Operator Characteristics (ROC) allowed to identify specific plasma proteins differentiating placebo responders from non-responders. These comprised immunoglobulins (IGHM, IGKV1D-16, IGHV3-23, IGHG1) and MASP2, related to regulation of complement activation, as well as proteins involved in oxidation reduction processes (QSOX1, CP TXN). This proof-of-concept study indicates that plasma proteomics are a promising tool to identify molecular correlates and predictors of the placebo effect in humans.

neuroscience↗