Molecule Information

General Information of the Molecule (ID: Mol04304)

• Name: Malonyl-CoA decarboxylase, mitochondrial (MLYCD) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: MLYCD
• Gene ID: 23417
• Sequence:
  MRGFGPGLTARRLLPLRLPPRPPGPRLASGQAAGALERAMDELLRRAVPPTPAYELREKT
  PAPAEGQCADFVSFYGGLAETAQRAELLGRLARGFGVDHGQVAEQSAGVLHLRQQQREA
  A VLLQAEDRLRYALVPRYRGLFHHISKLDGGVRFLVQLRADLLEAQALKLVEGPDVREM
  NG VLKGMLSEWFSSGFLNLERVTWHSPCEVLQKISEAEAVHPVKNWMDMKRRVGPYRRC
  YFF SHCSTPGEPLVVLHVALTGDISSNIQAIVKEHPPSETEEKNKITAAIFYSISLTQQ
  GLQG VELGTFLIKRVVKELQREFPHLGVFSSLSPIPGFTKWLLGLLNSQTKEHGRNELF
  TDSEC KEISEITGGPINETLKLLLSSSEWVQSEKLVRALQTPLMRLCAWYLYGEKHRGY
  ALNPVA NFHLQNGAVLWRINWMADVSLRGITGSCGLMANYRYFLEETGPNSTSYLGSKI
  IKASEQV LSLVAQFQKNSKL
• Function: Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In thefatty acid biosynthesis MCD selectively removes malonyl-CoA and thusassures that methyl-malonyl-CoA is the only chain elongating substratefor fatty acid synthase and that fatty acids with multiple methyl sidechains are produced. In peroxisomes it may be involved in degradingintraperoxisomal malonyl-CoA, which is generated by the peroxisomalbeta-oxidation of odd chain-length dicarboxylic fatty acids. Plays arole in the metabolic balance between glucose and lipid oxidation inmuscle independent of alterations in insulin signaling. May play a rolein controlling the extent of ischemic injury by promoting glucoseoxidation. {ECO:0000269|PubMed:10455107, ECO:0000269|PubMed:15003260,ECO:0000269|PubMed:18314420, ECO:0000269|PubMed:23482565}.
• Uniprot ID: DCMC_HUMAN
• Ensembl ID: ENSG000001031507
• HGNC ID: HGNC:7150

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

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Bladder cancer [ICD-11: 2C94.0] [1]

• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Fatty acid biosynthesis; Activation; hsa00061
• In Vitro Model: J82 cells; Bladder; Homo sapiens (Human); CVCL_0359
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Trypan blue exclusion assay; XTT assay
• Mechanism Description: Metabolomics analyses in our lab's gemcitabine- and cisplatin-resistant cell lines revealed increased phosphoglycerate dehydrogenase (PHGDH) expression in gemcitabine-resistant cells compared with parental cells. Isocitrate dehydrogenase 2 (IDH2) gain of function stabilized hypoxia-inducible factor1alpha (HIF1alpha) expression, stimulating aerobic glycolysis. In gemcitabine-resistant cells, elevated fumaric acid suppressed prolyl hydroxylase domain-containing protein 2/Egl nine homolog 1 (PHD2) and stabilized?HIF1alpha?expression.?PHGDH?downregulation or inhibition in gemcitabine-resistant BC cells inhibited their proliferation, migration, and invasion. Cisplatin-resistant cells showed elevated fatty acid metabolism, upregulating fatty acid synthase (FASN) downstream of tyrosine kinase. Using the fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor erdafitinib, we inhibited malonyl-CoA production, which is crucial for fatty acid synthesis, and thereby suppressed upregulated HIF1alpha expression.

References

• Ref 1: Targeting metabolic reprogramming to overcome drug resistance in advanced bladder cancer: insights from gemcitabine- and cisplatin-resistant models. Mol Oncol. 2024 Sep;18(9):2196-2211.