Lipoid Acid
Cofactors

Author: Gianpiero Pescarmona
Date: 05/03/2016

Description

STRUCTURE

METABOLISM

Nebraska

Targeting mitochondrial oxidative stress through lipoic acid synthase: a novel strategy to manage diabetic cardiovascular disease.2012

Lipoic acid (LA) is a potent mitochondrial antioxidant and an essential cofactor of α-ketoacid dehydrogenases.

Erythropoiesis and iron sulfur cluster biogenesis., 2010
ISCA and C1orf69 are thought to assemble Fe-S clusters for mitochondrial aconitase and for lipoate synthase, the enzyme producing lipoate for pyruvate dehydrogenase complex (PDC). PDC and aconitase are involved in the production of succinyl-CoA, a substrate for heme biosynthesis. Thus, many steps of heme synthesis depend on Fe-S cluster assembly.

TRANSPORT

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Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and E. 2007

In most cases (with the exception of the sodium-dependent multivitamin transporter for biotin, pantothenic acid, and lipoic acid), the vitamins are transported by separate carriers through the blood-brain barrier or choroid plexus.


Sodium dependent multivitamin transporter (SMVT): a potential target for drug delivery. 2015

Sodium dependent multivitamin transporter (SMVT; product of the SLC5A6 gene) is an important transmembrane protein responsible for translocation of vitamins and other essential cofactors such as biotin, pantothenic acid and lipoic acid.

FUNCTION

LA is covalently bound to the ε-amino group of lysine residues and functions as a cofactor for mitochondrial enzymes by catalyzing the oxidative decarboxylation of pyruvate, α-ketoglutarate and branched-chain α-keto acids. LA and its reduced form - dihydrolipoic acid (DHLA), meet all the criteria for an ideal antioxidant because they can easily quench radicals, can chelate metals, have an amphiphlic character and they do not exhibit any serious side effects. They interact with other antioxidants and can regenerate them. For this reason, LA is called an antioxidant of antioxidants. LA has an influence on the second messenger nuclear factor κB (NF-κB) and attenuates the release of free radicals and cytotoxic cytokines. Lipoic acid - biological activity and therapeutic potential., 2011

GSH and Thioredoxin??

The role of R-α-lipoic acid as a cofactor (lipoyllysine) in mitochondrial energy metabolism is well established. Lipoic acid non-covalently bound and exogenously administered to cells or supplemented in the diet is a potent modulator of the cell's redox status. The diversity of beneficial effects of lipoic acid in a variety of tissues can be mechanistically viewed in terms of thiol/disulfide exchange reactions that modulate the environment's redox and energy status. Lipoic acid-driven thiol/disulfide exchange reactions appear critical for the modulation of proteins involved in cell signaling and transcription factors. This review emphasizes the effects of lipoic acid on PI3K and AMPK signaling and related transcriptional pathways that are integrated by PGC-1α, a critical regulator of energy homoestasis. The effects of lipoic acid on the neuronal energy-redox axis are largely reviewed in terms of their outcomes for aging and age-related neurodegenerative diseases.

Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. 2011

Cofactor of PDH

Cofactor of alphaKGDH

Redox cycling

Bone metabolism

Emerging role of alpha-lipoic acid in the prevention and treatment of bone loss, 2015

Comments
2016-07-13T21:30:31 - Gianpiero Pescarmona

lipoic acid aconitase

lipoic acid ageing

serum glycine ageing

Glycine increases with ageing according to Puccinelli
Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects. 2003


Thyrotropin-releasing hormone (TRH)-Gly conversion to TRH in rat ventral prostate is inhibited by castration and aging. 1989

The serum testosterone concentration did not change with aging, but serum T4 levels fell significantly. 2014


Dietary vitamin D deficiency in rats from middle to old age leads to elevated tyrosine nitration and proteomics changes in levels of key proteins in brain: implications for low vitamin D-dependent age-related cognitive decline.
Given that VitD deficiency is especially widespread among the elderly, it is important to understand how the range of serum VitD levels that mimic those found in humans (from low to high) affects the brain during aging from middle-age to old-age.

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