3-Hydroxybutyric Acid Interacts with Lipid Monolayers at Concentrations That Impair Consciousness

Abstract

3-Hydroxybutyric acid (also referred to as β-hydroxybutyric acid or BHB), a small molecule metabolite whose concentration is elevated in type I diabetes and diabetic coma, was found to modulate the properties of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) monolayers when added to the subphase at clinical concentrations. This is a key piece of evidence supporting the hypothesis that the anesthetic actions of BHB are due to the metabolite's abilities to alter physical properties of cell membranes, leading to indirect effects on membrane protein function. Pressure-area isotherms show that BHB changes the compressibility of the monolayer and decrease the size of the two-phase coexistence region. Epi-fluorescent microscopy further reveals that the reduction of the coexistence region is due to the significant reduction in morphology of the liquid condensed domains in the two-phase coexistence region. These changes in monolayer morphology are associated with the diminished interfacial viscosity of the monolayers (measured using an interfacial stress rheometer), which gives insight as to how changes in phase and structure may contribute to membrane function.

Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

“…Nevertheless, research investigating the utilization of ketones is limited in AD; one study indicated a modest increase in SCOT expression (catabolizes ketone bodies into Acetyl-CoA and generates ATP), while the expression of HADHA and SCHAD (enzymes involved in fatty acid oxidation and ketogenesis) was significantly increased 3x in TgAD brain [46]. Although many studies reported the neuroprotective effect of ketogenic diets [47], the continued accumulation of 3-hydroxybutyric acid from non-dietary sources could diminish the interfacial viscosity of membrane lipids and modulate ion channels and thus disturb higher brain function [48, 49]. Furthermore, our findings shown that cognitive impairment was associated with serine level aberrations after chronic stress.…”

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes

“…Klebsiella pneumoniae has a similar metabolism association to Klebsiella quasipneumoniae , and it has been shown to induce the generation of inflammatory immune cells that can migrate to distant inflammatory tissues in the context of a genetically susceptible host where it takes part in the onset and progression of non-intestinal inflammatory diseases, such as arthritis 40 . In addition, the concentration of 3-hydroxybutyric acid is elevated in individuals with type I diabetes and diabetic coma 41 , and threonic acid is involved in calcium absorption 42 , indicating their potential discriminative roles and functional relevance in osteoporosis and subtypes.…”

Mechanical Properties of 3-Hydroxybutyric Acid-Induced Vesicles

“…The previous study showed that a greater portion of 3-hydroxybutyric acid induced higher fluid [ 5 ]. In that research, the transition from solid to liquid happened in the solid phase.…”

“…Furthermore, 3-hydroxybutyric acid has been reported to be an anesthetic in animals and has been reported to modulate the glycine-receptor function [ 4 ]. The anesthetic action was caused by the compound to modify mechanical behaviors of cell membranes to modulate the membrane protein function [ 5 ].…”