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Carbohydrate metabolism
Published in Martin Andrew Crook, Clinical Biochemistry & Metabolic Medicine, 2013
Non-glucose-reducing substances are identified by chromatography and specific tests. The significance of a Clinitest-positive result varies with the substances, which are as follows. Glucose.Glucuronates are relatively common urinary reducing substances. Numerous drugs, such as salicylates and their metabolites, are excreted in the urine after conjugation with glucuronate in the liver.Galactose is found in the urine in galactosaemia.Fructose may appear in the urine after very large oral doses of sucrose, or after excessive fruit ingestion, but usually fructosuria is due to one of two rare inborn errors of metabolism, both transmitted as autosomal recessive disorders: – essential fructosuria is usually a benign condition (hepatic fructokinase deficiency),– hereditary fructose intolerance is characterized by hypoglycaemia that may lead to death in infancy.Lactose. Lactosuria may occur in: – late pregnancy and during lactation,– lactase deficiency.Pentoses. Pentosuria is very rare. It may occur in: – alimentary pentosuria, after excessive ingestion of fruits such as cherries and grapes – the pentoses are arabinose and xylose,– essential pentosuria, a rare recessive disorder due to L-xylulose reductase deficiency, characterized by the excretion of xylose – it is usually benign.Homogentisic acid appears in the urine in the rare inborn error alkaptonuria. It is usually recognizable because it forms a blackish precipitate in urine on standing. Urea and creatinine may give weak positive results at high concentrations.
Emerging therapeutic targets for NASH: key innovations at the preclinical level
Published in Expert Opinion on Therapeutic Targets, 2020
Sugars are the primary substrate source for DNL, and increased fructose consumption in particular has been linked to the development of the metabolic syndrome and progression to NASH [29–31]. Ketohexokinase is the first and rate-limiting enzyme in the glycolytic breakdown of fructose into Acetyl-CoA [18] and mice deficient in ketohexokinase are protected from metabolic syndrome and also show reduced liver weight compared to wild-type animals [32,33]. Fructose is not only fueling DNL [34] but also negatively regulates fatty acid oxidation by inhibition of carnitine-palmitoyl-transferase 1 (CPT1) activity, suppression of mitochondrial function and post-translational modification of mitochondrial proteins [33] – all changes which are abolished upon knockout of ketohexokinase. As the deficiency of ketohexokinase in humans causes essential fructosuria, a harmless and asymptomatic disease [35], the pharmacologic inhibition of ketohexokinase might be a safe approach in treating NAFLD and NASH. Although no data are publically available on liver inflammation, fibrosis or hepatocarcinogenesis in pre-clincal models of NASH upon targeting of ketohexokinase, one ketohexokinase inhibitor, PF-06835919, has already entered early clinical testing for NASH (NCT03969719) and preliminary results recently suggested decreased liver fat and a trend for improved metabolic function [36].