Coenzyme A is an indispensable cofactor in living cells, synthesized from pantothenic acid (vitamin B5), adenosine triphosphate (ATP), and cysteine [1]. As an acyl carrier and carbonyl activating group, Coenzyme A plays a crucial role in the oxidation of pyruvate in the citric acid cycle and the metabolism of carboxylic acids (including short-chain and long-chain fatty acids) [2]. Abnormalities in the biosynthesis and homeostasis of Coenzyme A and its derivatives are associated with various human diseases, including cancer, diabetes, and neurodegeneration [3].
In vitro, supplementing Coenzyme A (25μM; 30 days) in the culture medium can significantly restore the function and mitochondrial respiratory activity of neuronal cells from patients with Pantothenate kinase-associated neurodegenerative disease (PKAN), while inhibiting neuronal death and ROS formation [4]. Coenzyme A (1mM; 30min) can completely inhibit the activity of peroxiredoxin 5 (Prdx5), and this inhibitory state can be relieved by dithiothreitol (DTT) reduction [5].
References:
[1] Michal G, Bergmeyer H U. Coenzyme A[M]//Methods of enzymatic analysis. Academic Press, 1974: 1967-1987.
[2] Leonardi R, Zhang YM, Rock CO, Jackowski S. Coenzyme A: back in action. Prog Lipid Res. 2005;44(2-3):125-153.
[3] Tsuchiya Y, Peak-Chew SY, Newell C, et al. Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells. Biochem J. 2017;474(14):2489-2508. Published 2017 Jul 11.
[4] Orellana DI, Santambrogio P, Rubio A, et al. Coenzyme A corrects pathological defects in human neurons of PANK2-associated neurodegeneration. EMBO Mol Med. 2016;8(10):1197-1211.
[5] Baković J, Yu B Y K, Silva D, et al. A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification[J]. Molecular and cellular biochemistry, 2019, 461(1): 91-102.
Coenzyme A是一种活细胞中不可或缺的辅因子，由泛酸（维生素B5）、三磷酸腺苷（ATP）和半胱氨酸合成 [1]。Coenzyme A作为酰基载体和羰基活化基团，在柠檬酸循环中丙酮酸的氧化以及羧酸（包括短链和长链脂肪酸）的代谢过程中起重要作用 [2]。Coenzyme A及其衍生物的生物合成和稳态异常与多种人类疾病有关，包括癌症、糖尿病和神经退行性变 [3]。
在体外，在培养基中补充Coenzyme A（25μM; 30 days）能够显著恢复来自Pantothenate激酶相关神经退行性疾病（PKAN）患者的神经元细胞的功能和线粒体呼吸活性，同时抑制神经元死亡和ROS形成 [4]。Coenzyme A（1mM; 30min）能够完全抑制过氧化物酶5（Prdx5）的活性，这种抑制状态可通过二硫苏糖醇（DTT）还原来解除 [5]。