Disease relevance of beta-hydroxybutyrate

• Long-term infusion of glucose, beta-hydroxybutyrate, and glycerol into the third ventricle of the rat brain caused a stabilization of body weight at a lower than normal level [1].
• Among the animals treated with beta-hydroxybutyrate the weight loss was unaccompanied by a reduction in food intake [1].
• A reduced respiratory quotient, together with elevated beta-hydroxybutyrate and reduced plasma fatty acid levels, suggests that the mutants oxidize a greater proportion of fat than wild-type mice, and that this possibly accounts for the resistance to diet-induced obesity [2].
• To explore the metabolic aspects of chronic liver disease, diurnal changes of arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox potential, were investigated in normal subjects, patients with chronic liver disease (Child's class A or B), and patients with hepatic failure (Child's class C) [3].
• A poly-beta-hydroxybutyrate complex extracted from the plasma membranes of genetically competent Escherichia coli contained polyhydroxybutyrate:polyphosphate:calcium in molar ratios approximating 1:1:0 [4].

Psychiatry related information on beta-hydroxybutyrate

• Multiple regression analysis revealed significant effects of body weight and beta-hydroxybutyric acid, respectively, on such specific depressive symptoms as depressed or dysphoric mood when controlling for severity of psychopathology of the eating disorder [5].
• To determine the tolerance limit of the liver in the critically suppressed mitochondrial oxidation-reduction state, the arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), which reflects hepatic mitochondrial oxidation-reduction potential, was measured 1319 times in 161 patients during the postoperative critical period [6].
• Elevated blood values of beta-hydroxybutyric acid and free fatty acids were observed in the majority of patients with bulimia and anorexia nervosa [7].
• Plasma NEFA and 3-hydroxybutyrate increased with food deprivation in all groups, the effect being highest in 20 day pregnant rats [8].
• The impact of a new test on the market, the beta-hydroxybutyric acid (BOH) assay, on clinical decision-making in the emergency department (ED) has not been well studied [9].

High impact information on beta-hydroxybutyrate

• Here we show that homozygous, but not heterozygous, mice deficient in Glut-2 are hyperglycaemic and relatively hypo-insulinaemic and have elevated plasma levels of glucagon, free fatty acids and beta-hydroxybutyrate [10].
• In addition, somatostatin resulted in a fivefold increase in beta-hydroxybutyrate and a 40 to 45 per cent rise in branched-chain amino acids (P less than 0.005) [11].
• Because intravenous infusion of beta-hydroxybutyrate (beta-OHB) has been reported to decrease urinary nitrogen excretion, we investigated in vivo metabolism of leucine, an essential amino acid, using L-[1-13C]leucine as a tracer during beta-OHB infusion [12].
• Serum FFA, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, insulin, and glucagon changed similarly in the two groups during exercise at base line, 1 and 6 wk [13].
• In all the pregnant women final levels of FFA and beta-hydroxybutyrate were strongly correlated and inversely related to final levels of plasma glucose [14].

Chemical compound and disease context of beta-hydroxybutyrate

• The beta-hydroxybutyrate/acetoacetate ratio in the tumor-venous blood rose with decreasing tumor blood flow indicating the development of hypoxia at advanced growth stages [15].
• We examined the impact of selectively elevating portal vein concentrations of lactate, pyruvate, or beta-hydroxybutyrate (BHB) on the sympathoadrenal response to insulin-induced hypoglycemia [16].
• Serum IGF-1 was correlated strongly with serum beta-hydroxybutyrate and body weight (r = -0.88 and 0.91, respectively, P less than 0.0001), and less strongly with serum glucose (r = -0.59, P less than 0.0002) [17].
• Plasma lactate and beta-hydroxybutyrate concentrations were measured during episodes of ketoacidosis and lactic acidosis in diabetics [18].
• 1,3-Butanediol (BD) is converted in the body to beta-hydroxybutyrate, and previous studies have shown that hyperketonemia had beneficial effects in experimental models of generalized hypoxia [19].

Biological context of beta-hydroxybutyrate

• The decrease in the acetoacetate/beta-hydroxybutyrate ratio of the liver was attributed to a restricted mitochondrial reoxidation of NADH due to an inhibition of oxidative phosphorylation [20].
• (1) In the Ca2+ pulse method, between 3.5 and 4.0 molecules of 3-hydroxybutyrate and 1.75 to 2.0 Ca2+ ions were accumulated per 2 e- per site during Ca2+ induced electron transport in the presence of rotenone, when measured under conditions in which movements of endogenous phosphate were negligible [21].
• Thus, unrestrained lipolysis can produce beta-hydroxybutyrate in sufficient quantities to induce a clinically measurable amount of HbF [22].
• Fasting these mice for 16 or 30 h resulted in lower levels of hepatic PEPCK mRNA, blood glucose, beta-hydroxybutyrate, blood urea nitrogen, and gluconeogenesis when compared with control mice [23].
• The response of Krebs cycle activity to exercise in insulin-deficient muscle might have been inadequate, as suggested by the increased 3-hydroxybutyrate/acetoacetate ratio in the venous blood observed in the normal controls but not in the diabetics [24].

Anatomical context of beta-hydroxybutyrate

• Changes in the free NAD+/NADH ratio and the energy charge (ATP + 1/2 ADP/ATP + ADP + AMP) of the liver were compared with the ratio of acetoacetate to beta-hydroxybutyrate of arterial blood in rabbits subjected to ligation of the common bile duct [20].
• Putative structure and functions of a poly-beta-hydroxybutyrate/calcium polyphosphate channel in bacterial plasma membranes [4].
• Ketogenesis and beta-hydroxybutyrate dehydrogenase activity were also lower in tumor H-252 mitochondria [25].
• After starvation for 24 hr, the plasma beta-hydroxybutyrate concentration was decreased in rats with bile duct ligation as compared with control rats [26].
• We have measured P/O ratios in rat liver mitochondria by the ADP pulse method and by 32 Pi esterification, measuring oxygen uptake with an oxygen electrode, and find values close to 2 with beta-hydroxybutyrate as substrate and 1.3 with succinate as substrate in the presence of rotenone to inhibit NADH oxidation [27].

Associations of beta-hydroxybutyrate with other chemical compounds

• After insulin was withdrawn, plasma beta-hydroxybutyrate, glycerol, and FFA all rose to higher levels (P less than 0.01) than those observed during infusion of somatostatin alone when growth hormone secretion was suppressed; no difference in plasma glucose, alanine, and glucagon levels was evident [28].
• In non-pregnant women plasma levels of glucose, alanine, free fatty acids (FFA) beta-hydroxybutyrate, insulin, and glucagon remained constant between 6 A.M. and noon except for slight fall in plasma alanine in the obese women and slight increases in beta-hydroxybutyrate in the lean [14].
• At pH 7.5, AQP9 proteoliposomes exhibited Hg(2+)-inhibitable glycerol and urea permeabilities that were increased 63-fold and 90-fold over background. beta-Hydroxybutyrate permeability was not increased above background, and osmotic water permeability was only minimally elevated [29].
• Lactate production, a cytosolic function, was increased fivefold in bile duct ligation, and both the lactate/pyruvate and the beta-hydroxybutyrate/aceto-acetate ratios were increased in the liver perfusate of bile duct-ligated rats [30].
• Ketonemia, elevated cerebral glucose and beta-hydroxybutyrate concentrations, and increased glycerophosphate dehydrogenase activity in brain suggest possible explanations for the beneficial action of adrenocorticotropic hormone and glucocorticoids in the treatment of infantile myoclonic epilepsy and other neurological disorders [31].

Gene context of beta-hydroxybutyrate

• Fatty acid oxidation, as inferred from serum beta-hydroxybutyrate levels, was increased in response to fasting, although the increase in L-Fabp-/- mice was significantly reduced in comparison to wild-type controls, despite comparable induction of PPAR alpha target genes [32].
• Plasma samples were analyzed for glucose, insulin, fatty acids, 3-hydroxybutyrate, triacylglycerol, pancreatic polypeptide, peptide YY, and cholecystokinin [33].
• Fasting glucose, insulin, and triglycerides were unchanged in the transgenic mice; leptin and beta-hydroxybutyrate levels were 91% and 29% higher, respectively [34].
• Beta-hydroxybutyrate-induced growth inhibition and collagen production in HK-2 cells are dependent on TGF-beta and Smad3 [35].
• Although a sigma54 consensus sequence was identified in the region between S1 and S2, a corresponding transcript was not detected, and a rpoN mutant of R. meliloti was able to utilize 3-hydroxybutyrate as a sole carbon source [36].

Analytical, diagnostic and therapeutic context of beta-hydroxybutyrate

• Fasting levels of beta-hydroxybutyrate rose in the calorie-restricted group (290 +/- 240 microM wk 1 vs. 780 +/- 30 microM wk 2) but not in the control group (P less than 0.01) [37].
• A 10% emulsion of FC-75 in a modified Tyrode solution, containing 3.5% bovine serum albumin, amino acids, nucleosides, and beta-hydroxybutyrate appeared to allow an adequate perfusion for at least seven hours [38].
• Increased total ketoacid levels (acetoacetate plus 3-hydroxybutyrate) correlated with increased free fatty acid levels (p = 0.0001), decreased C-peptide levels (p = 0.002), and increased body mass index (p = 0.002) (r2 = 0.72) [39].
• OBJECTIVE: The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies [40].
• Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036) [41].

References