China
Africa
Explore chapters and articles related to this topic
Metabolic Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephanie Grünewald, Alex Broomfield, Callum Wilson
Ketone bodies acetoacetate and 3-hydroxybutyric acid are metabolites derived from fatty acids and ketogenic amino acids, such as leucine. They are mainly produced in the liver, via reactions catalysed by the ketogenic enzymes HMG CoA synthase and HMG CoA lyase. After prolonged starvation, ketone bodies can provide up to two-thirds of the brain’s energy requirements. The rate-limiting enzyme of ketone body utilisation (ketolysis) is succinylcoenzyme A: 3-oxoacid coenzyme A transferase. The subsequent step of ketolysis is catalysed by 2-methylactoacetyl-coenzyme A thiolase (beta-ketothiolase), which is also involved in isoleucine catabolism.
Effects of Coffee and Caffeine Consumption on Serum Lipids and Lipoproteins
Published in Barry D. Smith, Uma Gupta, B.S. Gupta, Caffeine and Activation Theory, 2006
Ming Wei, Harvey A. Schwertner
Post, de Wit, and Princen (1997) studied the effects of cafestol and a mixture of cafestol, kahweol, and isokahweol (5 w/w) (Jacobsen & Thelle, 1987b; Jansen et al., 1995) on bile acid synthesis and on cholesterol 7-alpha-hydroxylase and sterol 27-hydroxylase activities in cultured rat hepatocytes. Dose-dependent decreases in bile acid mass production, cholesterol 7 alpha-hydroxylase activities, and sterol 27-hydroxylase activities were found when 20 μg/ml of cafestol was given. Maximal reductions of bile acid mass production, cholesterol 7 alpha-hydroxylase activities, and sterol 27-hydroxylase activities were −91, −79, and −49%, respectively. The mixture of cafestol, kahweol, and isokahweol was less potent in suppression of bile acid synthesis and cholesterol 7-alpha-hydroxylase activity. LDL-receptor, HMG-CoA reductase, and HMG-CoA synthase mRNAs were also significantly decreased by cafestol (−18, −20, and −43%, respectively).
Associations between ketone bodies and fasting plasma glucose in individuals with post-pancreatitis prediabetes
Published in Archives of Physiology and Biochemistry, 2020
Sakina H. Bharmal, Sayali A. Pendharkar, Ruma G. Singh, David Cameron-Smith, Maxim S. Petrov
Insulin has a stimulatory effect on cholesterol synthesis (Lakshmanan et al.1973). Evidence from pre-clinical and clinical studies has demonstrated that mevalonate (a biomarker of cholesterol synthesis) is inversely associated with BHB (Parker et al.1984, Kemper et al.2015). In the present study, BHB changed by −0.55 mmol/L (p = .008) with every unit change in LDL:HDL cholesterol, in individuals with PPP. This inverse association between BHB and LDL:HDL cholesterol can be explained by the insulin’s regulation of the cholesterol biosynthetic pathway. Cholesterol is synthesised from acetyl-CoA. The enzyme HMG-CoA synthase catalyses the conversion of acetyl-CoA to HMG-CoA, which is the intermediary step in both ketogenesis and cholesterol synthesis (Liscurn 2002). There are two forms of the HMG-CoA enzyme, of which one is involved in ketogenesis whereas the other catalyses the conversion of HMG-CoA to mevalonate (Liscurn 2002). Given that the initial steps of ketone and cholesterol synthesis are identical, it is conceivable that, in PPP, high plasma levels of insulin modulate the cAMP-dependent signal transduction pathway (Bruss 1997, Omar et al.2009) to favour synthesis of mevalonate and subsequently cholesterol.
Effect of Raw Crushed Garlic (Allium sativum L.) on Components of Metabolic Syndrome
Published in Journal of Dietary Supplements, 2018
Prema Ram Choudhary, Rameshchandra D. Jani, Megh Shyam Sharma
There are several explanations for the effect of numerous garlic preparations on components of metabolic syndrome. The mechanism of action of garlic in lowering serum lipids may be delayed lipid absorption from the gastrointestinal tract and decreased LDL cholesterol synthesis by the liver (Afkhami-Ardekani et al., 2006). Garlic has a sulphur-containing compound, allin, which is converted to an active ingredient, allicin, when the garlic bulb is crushed. This compound has an inhibitory effect on the key enzymes involved in cholesterol biosynthesis, such as Hydroxymethylglutaryl-CoA (HMG-CoA) synthase. Hypocholesterolemic effect of garlic is exerted by decreasing hepatic cholesterol biosynthesis; the triglyceride-lowering effect appears to be due to the inhibition of fatty acid synthesis by mallic enzymes, fatty acid synthase, and glucose-6 phosphate dehydrogenase. Among water-soluble compounds, S-allylcysteine, S-ethylcycteine, and S-propylcycteine reduce cholesterol synthesis like diallylsulphide, diallyldisulphide, diallytrisulphid, dipropylsulphide, and di-propyldisulphide inhibit cholesterol synthesis by 10%–15% (Choudhary et al., 2013).
ETC-1002 (Bempedoic acid) for the management of hyperlipidemia: from preclinical studies to phase 3 trials
Published in Expert Opinion on Pharmacotherapy, 2019
M. Ruscica, M. Banach, A. Sahebkar, A. Corsini, C. R. Sirtori
ETC-1002 (8-hydroxy-2,2,14,14-tetramethylpentadecaned–ioic acid; bempedoic acid) (Figure 1), whose synthesis has been reviewed elsewhere [24], is an oral, once-daily, small molecule with a half-life of 15–24 h and a log P of 3.65. It is rapidly absorbed in the small intestine (Box 1) [25]. ETC-1002 is a prodrug rapidly converted in the liver to a coenzyme A derivate, i.e. ETC-1200-CoA, metabolized by an endogenous liver acyl-CoA-synthetase. ETC-1002-CoA is the active metabolite responsible for the inhibition of ATP citrate lyase (ACLY), a cytosolic enzyme upstream of 3-hydroxy-3-methalglutaryl-coenzyme A reductase. ACLY possesses the unique feature to be positioned at the intersection of nutrient catabolism, cholesterol and fatty acid biosynthesis, thus connecting glucose metabolism to lipogenesis (Figure 1). By using a tricarboxylic acid cycle intermediate (citrate), ACL generates acetyl-CoA from mitochondrial citrate, ultimately transformed into HMG‐CoA and cholesterol [26]. ACLY is an extra-mitochondrial enzyme, highly expressed in lipogenic tissues, e.g. liver and adipose tissue, catalyzing the cleavage of mitochondrial-derived citrate to cytosolic acetyl-CoA and oxaloacetate; acetyl-CoA is the fundamental building block for both de novo cholesterol and fatty acid synthesis. Specifically, intramitochondrial citrate derived from glycolysis is transported to the cytoplasm, where endoplasmic reticulum-bound ACLY cleaves citrate to acetyl-CoA and oxaloacetate [27]. In subsequent steps of cholesterol biosynthesis two ACLY-derived acetyl-CoA units are condensed to acetoacetyl-CoA by HMG-CoA synthase and reduced to HMG-CoA by HMG-CoA reductase. Catalysis is initiated by autophosphorylation of the active-site histidine, generating an unstable citryl-phosphate. A covalent citryl–enzyme complex is formed. It is attacked by CoA to generate citryl-CoA and subsequently cleaved into acetyl-CoA and oxaloacetate [28] (detailed biochemical pathways are reviewed elsewhere) [29,30,31].