The Association Between Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Exposure and Key Cirrhosis-Related Outcomes.

Introduction: Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) may have hepatic benefits in patients with primarily chronic liver disease. ACE-I/ARB have not been evaluated in broad cohorts inclusive of those with decompensated cirrhosis. We analyzed the real-world association between ACE-I/ARB exposure and cirrhosis-related outcomes in a national cohort.

Association of psychosocial risk factors and liver transplant evaluation outcomes in metabolic dysfunction-associated steatotic liver disease.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a standardized psychosocial assessment tool used in liver transplantation (LT) evaluation and has been primarily studied in patients with alcohol-associated liver disease. We aimed to evaluate the relationship between SIPAT score and metabolic syndrome severity and LT waitlist outcomes in a large cohort of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We performed a single-center retrospective cohort study of patients with MASLD evaluated for LT from 2014 to 2021.

Waitlisting and liver transplantation for MetALD in the United States: An analysis of the UNOS national registry.

Background And Aims: The new steatotic liver disease (SLD) nomenclature introduced metabolic and alcohol-associated liver disease (MetALD), describing the intersection of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease. Waitlisting and liver transplantation for MetALD are not well defined. We aimed to develop and validate an algorithm for identifying SLD phenotypes and assessing trends in waitlisting and transplant outcomes.

Comprehensive Review of Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease.

Nonalcoholic Fatty Liver Disease (NAFLD) is a growing global phenomenon, and its damaging effects in terms of cardiovascular disease (CVD) risk are becoming more apparent. NAFLD is estimated to affect around one quarter of the world population and is often comorbid with other metabolic disorders including diabetes mellitus, hypertension, coronary artery disease, and metabolic syndrome. In this review, we examine the current evidence describing the many ways that NAFLD itself increases CVD risk.

Stereochemical and Mechanistic Investigation of the Reaction Catalyzed by Fom3 from Streptomyces fradiae, a Cobalamin-Dependent Radical S-Adenosylmethionine Methylase.

Fom3, a cobalamin-dependent radical S-adenosylmethionine (SAM) methylase, has recently been shown to catalyze the methylation of carbon 2″ of cytidylyl-2-hydroxyethylphosphonate (HEP-CMP) to form cytidylyl-2-hydroxypropylphosphonate (HPP-CMP) during the biosynthesis of fosfomycin, a broad-spectrum antibiotic. It has been hypothesized that a 5'-deoxyadenosyl 5'-radical (5'-dA) generated from the reductive cleavage of SAM abstracts a hydrogen atom from HEP-CMP to prime the substrate for addition of a methyl group from methylcobalamin (MeCbl); however, the mechanistic details of this reaction remain elusive. Moreover, it has been reported that Fom3 catalyzes the methylation of HEP-CMP to give a mixture of the ( S)-HPP and ( R)-HPP stereoisomers, which is rare for an enzyme-catalyzed reaction.

Enhanced Solubilization of Class B Radical S-Adenosylmethionine Methylases by Improved Cobalamin Uptake in Escherichia coli.

The methylation of unactivated carbon and phosphorus centers is a burgeoning area of biological chemistry, especially given that such reactions constitute key steps in the biosynthesis of numerous enzyme cofactors, antibiotics, and other natural products of clinical value. These kinetically challenging reactions are catalyzed exclusively by enzymes in the radical S-adenosylmethionine (SAM) superfamily and have been grouped into four classes (A-D). Class B radical SAM (RS) methylases require a cobalamin cofactor in addition to the [4Fe-4S] cluster that is characteristic of RS enzymes.

TsrM as a Model for Purifying and Characterizing Cobalamin-Dependent Radical S-Adenosylmethionine Methylases.

Cobalamin-dependent radical S-adenosylmethionine (SAM) methylases play vital roles in the de novo biosynthesis of many antibiotics, cofactors, and other important natural products, yet remain an understudied subclass of radical SAM enzymes. In addition to a [4Fe-4S] cluster that is ligated by three cysteine residues, these enzymes also contain an N-terminal cobalamin-binding domain. In vitro studies of these enzymes have been severely limited because many are insoluble or sparingly soluble upon their overproduction in Escherichia coli.