By Mulchand S. Patel, Lester Packer
The popularity of oxidative pressure as a significant factor in wellbeing and fitness, getting older, and affliction has ended in a surge in learn aimed toward uncovering powerful countermeasures within the kind of antioxidants. special in its two-fold protecting functionality, alpha-lipoic acid has drawn remarkable curiosity as a coenzyme in mitochondrial power metabolism and as an antioxidant and mobilephone redox modulator. Mounting info concerning its power healthiness merits calls for an authoritative, single-source connection with codify present wisdom and consultant destiny examine. A state-of-the-science compilation, Lipoic Acid follows the historical past of this effective coenzyme and the most recent discoveries concerning the chemistry, organic motion, and value in strength creation, antioxidant job, and overall healthiness. The ebook is split into 3 sections: · part I: Discovery and Molecular constitution stories the early experiences resulting in the invention of alpha-lipoic acid and explains the molecular constitution, biosynthesis, and the characterization of lipoic acid and its chemical derivatives. · part II: Metabolic facets describes intimately the human pharmacokinetics of alpha-lipoic acid together with the lipoic acid-derived dehydrogenase complexes and their roles in power metabolism. It additionally explains antioxidant job and redox modulation and the way lipoic acid induces section II detoxing enzymes via activation of Nrf2-dependent gene expression. · part III scientific features discusses enzyme deficiency issues and the results of lipoic acid on insulin. It defines lipoic acid effect on signaling pathways and AMP-activated kinase, and considers the healing implications for remedy of metabolic syndromes and the development of mitochondrial functionality by way of lipoic acid supplementation. Contributions from best foreign researchers make Lipoic Acid the main accomplished, up to date account of the impression of this most likely key molecule in diminishing the dangerous results of getting older and sickness.
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Additional info for Lipoic Acid: Energy Production, Antioxidant Activity and Health Effects (Oxidative Stress and Disease)
The reducing equivalents generated in each overall reaction are ultimately transferred to NADþ, affording NADH and a proton. The role of the lipoyl cofactor in the pyruvate and a-ketoglutarate dehydrogenase complexes (PDC and KDC, respectively) is well established [11–14]. Other complexes in which it is known to function in a similar capacity are the branched-chain a-keto acid dehydrogenase complex (BCKDC), which catalyzes the oxidative decarboxylation of the branched-chain a-keto acids that are derived from the transamination of valine, leucine, and isoleucine; the glycine cleavage system (GCS), which degrades glycine to NHþ 4 and CO2 with transfer of its a carbon to tetrahydrofolate, yielding N5, N10-methylene tetrahydrofolate; and the acetoin dehydrogenase complex (ADC), which catalyzes the oxidative cleavage of acetoin to acetaldehyde and acetyl-CoA, a reaction that allows certain bacteria to use acetoin as their sole carbon source [3–7].
The synthesis and use of regiospeciﬁc and stereospeciﬁc isotopically labeled forms of octanoic acid yielded further insights into the biosynthesis of lipoic acid. 3D), and subsequent isolation and determination of the 3H=14C ratio in the isolates showed that the ratio in the lipoic acid product was essentially unchanged from that in the precursor compounds, suggesting that hydrogens at carbons 5 and 7 are not removed during the process of sulfur insertion . 3 Structures of molecules used in metabolic labeling studies to probe the mechanism of lipoic acid biosynthesis: (A) [1-14C]octanoic acid; (B) [5(R,S)-3H]octanoic acid; (C) [7(R,S)-3H]octanoic acid; (D) [8-3H]octanoic acid; (E) [6(R)-3H]octanoic acid; (F) [6(S)-3H]octanoic acid.
Puriﬁcation and properties of the component enzymes of the pyruvate dehydrogenase complexes from bovine kidney and heart, Arch. Biochem. , 148, 327–342, 1972. 8. , A trail of research from lipoic acid to a-keto acid dehydrogenase complexes, J. Biol. , 276, 38329–38336, 2001. 2008 1:25pm Compositor Name: JGanesan 2 Lipoic Acid Biosynthesis Natasha M. Nesbitt, Robert M. Cicchillo, Kyung-Hoon Lee, Tyler L. Grove, and Squire J. Booker CONTENTS Lipoic Acid and Lipoyl Carrier Proteins ...........................................................