Poster Topical Area: Energy and Macronutrient Metabolism

Location: Hall D

Poster Board Number: 438

P10-038 - Identification of enzymes responsible for endogenous synthesis of erythritol from the pentose phosphate pathway

Monday, Jun 11
8:00 AM – 3:00 PM

Objective:  Non-targeted metabolomics experiments performed in a cohort of young adults followed over the course of their first year of college identified erythritol as a novel biomarker of central adiposity gain.  Erythritol levels in pooled plasma from individuals exhibiting central adiposity gain were nearly 15-fold higher than in plasma from individuals with stable adiposity and nearly 23-fold higher in individuals with higher glycemia compared to those with lower glycemia.  Erythritol is a four-carbon sugar and low-calorie sweetener/food additive that is rapidly absorbed then excreted in urine following ingestion.  Stable isotope tracer experiments demonstrated that erythritol is formed from reduction of erythrose, which is produced from erythrose-4-phosphate, a pentose phosphate pathway intermediate.  The objective of this study was to determine which enzymes are responsible for conversion of erythrose to erythritol.

Methods:  This study used column chromatography to purify two distinct enzyme activities from rabbit liver, which proteomic analysis identified as ADH1 and SORD using.  Recombinant human ADH1 (four variants) and SORD were expressed, purified, and kinetically characterized. 

Results:  Both human recombinant ADH1 and SORD reduce erythrose to erythritol, using either NADPH or NADH as co-factors.  Interestingly, ADH1 variants vary with respect to both their affinity for erythrose and turnover number.  Cell culture studies indicated that this activity is primarily NADPH-dependent in vivo.  Interestingly, the ADH1B2 variant, common in Asian populations, is not active with NADPH is used as a co-factor. 

Conclusions:  ADH1 catalyzes the first step of ethanol metabolism, and is known to have several human population-specific variants that markedly affect enzyme activity and alcohol metabolism capacity, suggesting that these variants may also account for population-specific variations in erythritol production from glucose and influence glucose utilization and central metabolism.

CoAuthors: Lisa Krämer – Technische Universität Braunschweig; Karsten Hiller – Technische Universität Braunschweig

Martha S. Field

Assistant Professor
Cornell University
Ithaca, New York