1.
Advances in synthesis of biotin and assembly of lipoic acid.
Cronan, JE
Current opinion in chemical biology. 2018;:60-66
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Abstract
Although biotin and lipoic acid are two universally conserved cofactors essential for intermediary metabolism, their synthetic pathways have become known only in recent years. Both pathways have unusual features. Biotin synthesis in Escherichia coli requires a methylation that is later removed whereas lipoic acid is assembled on the enzymes where it is required for activity by two different pathways.
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Alpha-lipoic acid (ALA) as a supplementation for weight loss: results from a meta-analysis of randomized controlled trials.
Kucukgoncu, S, Zhou, E, Lucas, KB, Tek, C
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2017;(5):594-601
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Abstract
OBJECTIVES Obesity is associated with significant morbidity and mortality rates. Even modest weight loss may be associated with health benefits. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant. Studies have suggested anti-obesity properties of ALA; however, results are inconsistent. The purpose of this study is to conduct a meta-analysis of the effect of ALA on weight and body mass index (BMI). METHODS A comprehensive, systematic literature search identified 10 articles on randomized, double-blind, placebo-controlled studies involving ALA. We conducted a meta-analysis of mean weight and BMI change differences between ALA and placebo treatment groups. RESULTS Alpha-lipoic acid treatment coincided with a statistically significant 1.27 kg (confidence interval = 0.25 to 2.29) greater mean weight loss compared with the placebo group. A significant overall mean BMI difference of -0.43 kg/ m2 (confidence interval = -0.82 to -0.03) was found between the ALA and placebo groups. Meta-regression analysis showed no significance in ALA dose on BMI and weight changes. Study duration significantly affected BMI change, but not weight change. CONCLUSIONS Alpha-lipoic acid treatment showed small, yet significant short-term weight loss compared with placebo. Further research is needed to examine the effect of different doses and the long-term benefits of ALA on weight management.
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Alpha lipoic acid: a new treatment for neuropathic pain in patients with diabetes?
Mijnhout, GS, Alkhalaf, A, Kleefstra, N, Bilo, HJ
The Netherlands journal of medicine. 2010;(4):158-62
Abstract
BACKGROUND Neuropathic pain is difficult to treat. We identified those studies in the literature in which the effectiveness of alpha lipoic acid as a treatment for neuropathic pain was evaluated. METHODS Systematic literature review. The databases MEDLINE and EMBASE were searched using the keywords 'lipoic acid', 'thioctic acid', 'diabet*', and the medical subject headings (MeSH ) 'thioctic acid' and 'diabetes mellitus'. Randomised placebo-controlled trials (RCTs) and meta-analyses were selected and assessed for their methodological quality. RESULTS Five RCTs and one meta-analysis were found. The Total Symptom Score (TSS) was used as the primary outcome measure. A significant improvement in the TSS was reported in four of the RCTs. An oral or intravenous alpha lipoic dose of at least 600 mg per day resulted in a 50% reduction in the TSS. However, compared with the control group, the TSS reduction in most groups was less than 30%, which is the threshold presumed to be clinically relevant. Four RCTs were of good quality (level of evidence 1b), one RCT had methodological limitations (level 2b), and the methodological quality of the meta-analysis was insufficient for the purposes of this review. CONCLUSION Based on the currently available evidence, when given intravenously at a dosage of 600 mg once daily over a period of three weeks, alpha lipoic acid leads to a significant and clinically relevant reduction in neuropathic pain (grade of recommendation A). It is unclear if the significant improvements seen after three to five weeks of oral administration at a dosage of >or= 600 mg daily are clinically relevant.
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2-Oxo acid dehydrogenase complexes in redox regulation.
Bunik, VI
European journal of biochemistry. 2003;(6):1036-42
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Abstract
A number of cellular systems cooperate in redox regulation, providing metabolic responses according to changes in the oxidation (or reduction) of the redox active components of a cell. Key systems of central metabolism, such as the 2-oxo acid dehydrogenase complexes, are important participants in redox regulation, because their function is controlled by the NADH/NAD+ ratio and the complex-bound dihydrolipoate/lipoate ratio. Redox state of the complex-bound lipoate is an indicator of the availability of the reaction substrates (2-oxo acid, CoA and NAD+) and thiol-disulfide status of the medium. Accumulation of the dihydrolipoate intermediate causes inactivation of the first enzyme of the complexes. With the mammalian pyruvate dehydrogenase, the phosphorylation system is involved in the lipoate-dependent regulation, whereas mammalian 2-oxoglutarate dehydrogenase exhibits a higher sensitivity to direct regulation by the complex-bound dihydrolipoate/lipoate and external SH/S-S, including mitochondrial thioredoxin. Thioredoxin efficiently protects the complexes from self-inactivation during catalysis at low NAD+. As a result, 2-oxoglutarate dehydrogenase complex may provide succinyl-CoA for phosphorylation of GDP and ADP under conditions of restricted NAD+ availability. This may be essential upon accumulation of NADH and exhaustion of the pyridine nucleotide pool. Concomitantly, thioredoxin stimulates the complex-bound dihydrolipoate-dependent production of reactive oxygen species. It is suggested that this side-effect of the 2-oxo acid oxidation at low NAD+in vivo would be overcome by cooperation of mitochondrial thioredoxin and the thioredoxin-dependent peroxidase, SP-22.