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Last update 08 May 2025

ACSS1

Last update 08 May 2025

Basic Info

Synonyms

ACAS2L, AceCS2, AceCS2L

+ [10]

Introduction

Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:16788062). Acetate is the preferred substrate (PubMed:16788062). Can also utilize propionate with a much lower affinity (By similarity). Provides acetyl-CoA that is utilized mainly for oxidation under ketogenic conditions (By similarity). Involved in thermogenesis under ketogenic conditions, using acetate as a vital fuel when carbohydrate availability is insufficient (By similarity).

Drugs associated with ACSS1

US12281084

Patent Mining

Target

ACSS1 x ACSS2

Mechanism

ACSS1 inhibitors [+1]

Active Org.

The Wistar Institute

Originator Org.

The Wistar Institute

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ACSS1

100 Translational Medicine associated with ACSS1

0 Patents (Medical) associated with ACSS1

116

Literatures (Medical) associated with ACSS1

01 May 2025·Free Radical Biology and Medicine

Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered liver lipid metabolism on a ketogenic diet

Article

Author: Zhou, Daohong ; Gius, David ; Li, Guiming ; Quan, Songhua ; Gao, Yucheng ; Han, Xianlin ; Pan, Meixia ; Wei, Sung-Jen ; Dong, Felix F ; Schell, Joseph ; Jiang, Haiyan ; Munkácsy, Erin ; Xu, Guogang ; Horikoshi, Nobuo

Acetyl-CoA Synthetase Short Chain Family Member-1 (ACSS1) catalyzes the ligation of acetate and coenzyme A to generate acetyl-CoA in the mitochondria to produce ATP through the tricarboxylic acid (TCA) cycle. We recently generated an ACSS1-acetylation (Ac) mimic knock-in mouse, where lysine 635 was mutated to glutamine (K635Q), which structurally and biochemically mimics an acetylated lysine. ACSS1 enzymatic activity is regulated, at least in part, through the acetylation of lysine 635 in mice (lysine 642 in humans), a Sirtuin 3 deacetylation target. We challenged our Acss1^K635Q knock-in mice with a three-week ketogenic diet. While both wild-type and Acss1^K635Q knock-in mice were in ketosis with similar blood glucose levels, the Acss1^K635Q mice exhibited elevated blood acetate and liver acetyl-CoA. In addition, and importantly, compared to wild-type mice, the liver in the Acss1^K635Q mice displayed a much more predominant liver steatosis morphology and accumulation of lipid drops, as measured by H&E and Oil Red O staining. RNAseq analysis identified that genes related to mitochondrial respiratory chain complexes and oxidative stress were significantly overexpressed in the Acss1^K635Q mice on a KD. Finally, lipidomics analysis revealed very different lipid profiles for these groups, including a dramatic increase in triacylglycerides (TAGs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and cardiolipins in the Acss1^K635Q liver.

01 Apr 2025·Journal of Bone Oncology

Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets

Review

Author: Yin, Zhiyang ; Fan, Minjie ; Zheng, Pengfei ; Shen, Guanlu

Osteosarcoma is a common bone tumor in adolescents, which is characterized by lipid metabolism disorders and plays a key role in tumorigenesis and disease progression. Ferroptosis is an iron-dependent form of programmed cell death associated with lipid peroxidation. This review provides an in-depth analysis of the complex relationship between lipid metabolic reprogramming and associated ferroptosis in OS from the perspective of metabolic enzymes and metabolites. We discussed the molecular basis of lipid uptake, synthesis, storage, lipolysis, and the tumor microenvironment, as well as their significance in OS development. Key enzymes such as adenosine triphosphate-citrate lyase (ACLY), acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1) are overexpressed in OS and associated with poor prognosis. Based on specific changes in metabolic processes, this review highlights potential therapeutic targets in the lipid metabolism and ferroptosis pathways, and in particular the HMG-CoA reductase inhibitor simvastatin has shown potential in inducing apoptosis and inhibiting OS metastasis. Targeting these pathways provides new strategies for the treatment of OS. However, challenges such as the complexity of drug development and metabolic interactions must be overcome. A comprehensive understanding of the interplay between dysregulation of lipid metabolism and ferroptosis is essential for the development of innovative and effective therapies for OS, with the ultimate goal of improving patient outcomes.

01 Mar 2025·The Journal of Steroid Biochemistry and Molecular Biology

Effects of combined exposure to 17α-methyltestosterone and polystyrene microplastics on lipid metabolism and the nervous system in Danio rerio

Article

Author: Cao, Lu ; Liu, Qing ; Li, Tongyao ; Liu, Shaozhen ; Song, Jing ; Wang, Weiwei ; Liu, Yu ; Xiong, Zijun ; Chen, Gen ; Zhao, Haiyan ; Wang, Xianzong ; Rong, Weiya

Polystyrene (PS) microplastics are pervasive environmental pollutants that are harmful to aquatic organisms upon degradation. The synthetic androgen 17α-methyltestosterone (MT) is an environmental endocrine-disrupting chemical. This study aimed to systematically evaluate the combined histological and molecular effects of MT and PS exposure on the liver and brain tissues of Danio rerio with focus on lipid metabolism and neural function disruption. Female D. rerio were exposed to 50 ng/L MT and 0.5 mg/L PS (5 μm in diameter) for 21 d. Histological observations, real-time quantitative PCR (qPCR), and RNA-sequencing (RNA-seq) analysis were employed to assess the effects of PS and MT. These results indicated that MT and PS co-exposure caused fatty degeneration of liver cells and a significant upregulation of lipid synthesis-related genes (ACSS1, CEL, FASN, and GK5). In brain tissue, the observed effects included reduced marginal layer neuron counts, cytoplasmic loosening of central layer neurons, disordered gray matter layer cells, and vascular congestion. RNA-seq analysis further revealed significant enrichment of differentially expressed genes in the "glycine, serine, and threonine metabolism" and "neuroactive ligand-receptor interaction" signaling pathways. Thus, MT and PS co-exposure induced lipid metabolism disorders in D. rerio and influence neural signaling by altering the "neuroactive ligand-receptor interaction" pathway. These findings highlight the complex risks posed by environmental pollutants to aquatic life and provide critical insights for environmental protection and aquatic health research.

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ACSS1

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