Molecule Information

General Information of the Molecule (ID: Mol04011)

• Name: Acyl-CoA oxidase 1 (ACOX1) ,Homo sapiens
• Synonyms: Palmitoyl-CoA oxidase; Peroxisomal fatty acyl-CoA oxidase; Straight-chain acyl-CoA oxidase
• Molecule Type: Protein
• Gene Name: ACOX1
• Gene ID: 51
• Location: chr17:75941507-75979177[-]
• Sequence:
  MNPDLRRERDSASFNPELLTHILDGSPEKTRRRREIENMILNDPDFQHEDLNFLTRSQRY
  EVAVRKSAIMVKKMREFGIADPDEIMWFKKLHLVNFVEPVGLNYSMFIPTLLNQGTTAQK
  EKWLLSSKGLQIIGTYAQTEMGHGTHLRGLETTATYDPETQEFILNSPTVTSIKWWPGGL
  GKTSNHAIVLAQLITKGKCYGLHAFIVPIREIGTHKPLPGITVGDIGPKFGYDEIDNGYL
  KMDNHRIPRENMLMKYAQVKPDGTYVKPLSNKLTYGTMVFVRSFLVGEAARALSKACTIA
  IRYSAVRHQSEIKPGEPEPQILDFQTQQYKLFPLLATAYAFQFVGAYMKETYHRINEGIG
  QGDLSELPELHALTAGLKAFTSWTANTGIEACRMACGGHGYSHCSGLPNIYVNFTPSCTF
  EGENTVMMLQTARFLMKSYDQVHSGKLVCGMVSYLNDLPSQRIQPQQVAVWPTMVDINSP
  ESLTEAYKLRAARLVEIAAKNLQKEVIHRKSKEVAWNLTSVDLVRASEAHCHYVVVKLFS
  EKLLKIQDKAIQAVLRSLCLLYSLYGISQNAGDFLQGSIMTEPQITQVNQRVKELLTLIR
  SDAVALVDAFDFQDVTLGSVLGRYDGNVYENLFEWAKNSPLNKAEVHESYKHLKSLQSKL
• Function: Involved in the initial and rate-limiting step of peroxisomal beta-oxidation of straight-chain saturated and unsaturated very-long- chain fatty acids (PubMed:15060085, PubMed:17458872, PubMed:17603022, PubMed:32169171, PubMed:33234382, PubMed:7876265). Catalyzes the desaturation of fatty acyl-CoAs such as palmitoyl-CoA (hexadecanoyl- CoA) to 2-trans-enoyl-CoAs ((2E)-enoyl-CoAs) such as (2E)-hexadecenoyl- CoA, and donates electrons directly to molecular oxygen (O(2)), thereby producing hydrogen peroxide (H(2)O(2)) (PubMed:17458872, PubMed:17603022, PubMed:7876265). .; [Isoform 1]: Shows highest activity against medium-chain fatty acyl-CoAs. Shows optimum activity with a chain length of 10 carbons (decanoyl-CoA) in vitro. .; [Isoform 2]: Is active against a much broader range of substrates and shows activity towards long-chain fatty acyl-CoAs. .
• Uniprot ID: ACOX1_HUMAN
• Ensembl ID: ENSG00000161533
• HGNC ID: HGNC:119

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Investigative Drug(s) 1 drug(s) in total

10,12-Tricosadiynoic Acid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Chronic lymphocytic leukemia [ICD-11: 2A82.0] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Chronic lymphocytic leukemia [ICD-11: 2A82.0]
• Resistant Drug: 10,12-Tricosadiynoic Acid
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HG3 cells; Blood; Homo sapiens (Human); CVCL_Y547
• In Vitro Model: MEC1 cells; Blood; Homo sapiens (Human); CVCL_1870
• In Vitro Model: OSU-CLL cells; Blood; Homo sapiens (Human); CVCL_Y382
• In Vitro Model: PGA1 cells; Blood; Homo sapiens (Human); CVCL_Y545
• In Vitro Model: Primary B-lymphocytes cells; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qPCR, immunoblot and confocal microscopy approaches
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Accordingly, downmodulation of ACOX1 (a rate-limiting pFAO enzyme overexpressed in CLL cells) was enough to shift the CLL cells' metabolism from lipids to a carbon- and amino-acid-based phenotype. Complete blockade of ACOX1 resulted in lipid droplet accumulation and caspase-dependent death in CLL cells, including those from individuals with poor cytogenetic and clinical prognostic factors.

References

• Ref 1: ACOX1-mediated peroxisomal fatty acid oxidation contributes to metabolic reprogramming and survival in chronic lymphocytic leukemia. Leukemia. 2024 Feb;38(2):302-317.