ACAT1: A Potential Drug Target and Biomarker for Mitochondrial Enzyme Dysfunction
ACAT1: A Potential Drug Target and Biomarker for Mitochondrial Enzyme Dysfunction
Mitochondria are critical organelles responsible for generating energy-producing molecules, including the majority of ATP, in the cells of the body. Mitochondrial dysfunction, characterized by impaired mitochondrial function and dysfunction, has been linked to a wide range of diseases, including neurodegenerative disorders, cardiomyopathies, and metabolic disorders. The ability to modulate the activity of mitochondrial enzymes has the potential to be a therapeutic approach for the treatment of these diseases. One such enzyme that has garnered significant attention in recent years is ACAT1 (mitochondrial acetoacetyl-CoA thiolase), a protein that plays a crucial role in the metabolism of acetyl-CoA, a key substrate for the citric acid cycle. In this article, we will explore the structure, function, and potential therapeutic applications of ACAT1.
Structure and Function
ACAT1 is a single-chain protein that contains 28 amino acid residues and 16% protein content. The protein has a molecular weight of 38 kDa and a calculated pI of 7.4. It is expressed in the mitochondria and is primarily localized to the inner mitochondrial membrane (IMM). ACAT1 functions as a co-factor for the enzyme Pyruvate Carrier (Pyruvate Translocation Factor 1, Pyruvate Carrier Protein, Pyruvate Carrier), which is responsible for transporting pyruvate across the IMM.
In addition to its role in the Pyruvate Translocation Factor, ACAT1 is involved in the metabolism of various other molecules, including fatty acids, ketones, and amino acids. It has been shown to regulate the levels of acetoacetyl-CoA in the mitochondria, which is a key substrate for the citric acid cycle. By regulating the levels of acetoacetyl-CoA, ACAT1 has been linked to the regulation of cellular energy metabolism and the potential to play a role in the treatment of metabolic disorders.
Potential Therapeutic Applications
The potential therapeutic applications of ACAT1 are vast and span a range of disease contexts. One of the most promising applications is the treatment of mitochondrial dysfunction associated with neurodegenerative disorders. neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, are characterized by progressive neurotoxicity and damage to brain cells, which is thought to be caused by dysfunction in the mitochondria.
ACAT1 has been shown to be highly expressed in the brains of individuals with neurodegenerative disorders, and modulating its activity has been shown to improve cellular energy metabolism and reduce neurotoxicity. In addition, ACAT1 has also been shown to be involved in the regulation of the levels of reactive oxygen species (ROS), which are highly reactive molecules that can damage cellular components and contribute to the development of neurodegenerative disorders.
ACAT1 has also the potential to be a biomarker for the diagnosis and monitoring of various metabolic disorders, such as obesity, diabetes, and cardiovascular disease. The obesity epidemic is a major contributor to the development of these disorders, and ACAT1 has been shown to be involved in the metabolism of fatty acids, which are a key substrate for the citric acid cycle.
In conclusion, ACAT1 is a protein that plays a crucial role in the metabolism of acetyl-CoA, a key substrate for the citric acid cycle. Its function as a co-factor for the Pyruvate Translocation Factor and its involvement in the regulation of acetoacetyl-CoA levels in the
Protein Name: Acetyl-CoA Acetyltransferase 1
Functions: This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA (PubMed:1715688, PubMed:7728148, PubMed:9744475). Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms (PubMed:1715688, PubMed:7728148, PubMed:9744475). The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA (PubMed:17371050). Thereby, it plays a major role in ketone body metabolism (PubMed:17371050, PubMed:1715688, PubMed:7728148, PubMed:9744475)
More Common Targets
ACAT2 | ACBD3 | ACBD4 | ACBD5 | ACBD6 | ACBD7 | ACCS | ACCSL | ACD | ACE | ACE2 | ACE2-DT | ACE3P | ACER1 | ACER2 | ACER3 | Acetyl-CoA Carboxylases (ACC) | Acetylcholine Receptors (Nicotinic) (nAChR) | ACHE | Acid-Sensing Ion Channel (ASIC) | ACIN1 | ACKR1 | ACKR2 | ACKR3 | ACKR4 | ACKR4P1 | ACLY | ACMSD | ACO1 | ACO2 | ACOD1 | ACOT1 | ACOT11 | ACOT12 | ACOT13 | ACOT2 | ACOT4 | ACOT6 | ACOT7 | ACOT8 | ACOT9 | ACOX1 | ACOX2 | ACOX3 | ACOXL | ACOXL-AS1 | ACP1 | ACP2 | ACP3 | ACP4 | ACP5 | ACP6 | ACP7 | ACR | ACRBP | ACRV1 | ACSBG1 | ACSBG2 | ACSF2 | ACSF3 | ACSL1 | ACSL3 | ACSL4 | ACSL5 | ACSL6 | ACSM1 | ACSM2A | ACSM2B | ACSM3 | ACSM4 | ACSM5 | ACSM6 | ACSS1 | ACSS2 | ACSS3 | ACTA1 | ACTA2 | ACTA2-AS1 | ACTB | ACTBL2 | ACTBP12 | ACTBP2 | ACTBP3 | ACTBP8 | ACTBP9 | ACTC1 | ACTE1P | ACTG1 | ACTG1P1 | ACTG1P10 | ACTG1P12 | ACTG1P17 | ACTG1P20 | ACTG1P22 | ACTG1P25 | ACTG1P4 | ACTG2 | Actin | Activating signal cointegrator 1 complex protein | Activin receptor type 2 (nonspecifed subtype)