Molecule Information

General Information of the Molecule (ID: Mol04085)

• Name: Aldolase B, fructose-bisphosphate (Aldolase B) ,Homo sapiens
• Synonyms: Liver-type aldolase
• Molecule Type: Protein
• Gene Name: ALDOB
• Gene ID: 229
• Location: chr9:101420560-101449664[-]
• Sequence:
  MAHRFPALTQEQKKELSEIAQSIVANGKGILAADESVGTMGNRLQRIKVENTEENRRQFR
  EILFSVDSSINQSIGGVILFHETLYQKDSQGKLFRNILKEKGIVVGIKLDQGGAPLAGTN
  KETTIQGLDGLSERCAQYKKDGVDFGKWRAVLRIADQCPSSLAIQENANALARYASICQQ
  NGLVPIVEPEVIPDGDHDLEHCQYVTEKVLAAVYKALNDHHVYLEGTLLKPNMVTAGHAC
  TKKYTPEQVAMATVTALHRTVPAAVPGICFLSGGMSEEDATLNLNAINLCPLPKPWKLSF
  SYGRALQASALAAWGGKAANKEATQEAFMKRAMANCQAAKGQYVHTGSSGAASTQSLFTA
  CYTY
• 3D-structure: PDB ID: 8D44; Classification: Hydrolase; Method: Electron microscopy; Resolution: 2.80 Å
• Function: Catalyzes the aldol cleavage of fructose 1,6-biphosphate to form two triosephosphates dihydroxyacetone phosphate and D- glyceraldehyde 3-phosphate in glycolysis as well as the reverse stereospecific aldol addition reaction in gluconeogenesis. In fructolysis, metabolizes fructose 1-phosphate derived from the phosphorylation of dietary fructose by fructokinase into dihydroxyacetone phosphate and D-glyceraldehyde (PubMed:10970798, PubMed:12205126, PubMed:20848650). Acts as an adapter independently of its enzymatic activity, exerts a tumor suppressor role by stabilizing the ternary complex with G6PD and TP53 to inhibit G6PD activity and keep oxidative pentose phosphate metabolism in check (PubMed:35122041). .
• Uniprot ID: ALDOB_HUMAN
• Ensembl ID: ENSG00000136872
• HGNC ID: HGNC:417

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

Approved Drug(s) 2 drug(s) in total

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: CRC patients; Homo Sapiens
• Experiment for Molecule Alteration: Immunohistochemical (IHC) staining
• Experiment for Drug Resistance: Overall survival assay (OS)
• Mechanism Description: This study has demonstrated that overexpression of ALDOB in CRC cells promotes lactagenesis by regulating PDK1 activation. The secreted lactate is then transported to neighboring cells and converted to pyruvate by lactate-induced LDHB, enhancing the ability of OXPHOS in terms of basal respiration and acting as a repressor of CEACAM6 expression. Consequently, ALDOB/lactate-mediated expression of CEACAM6 promotes cell proliferation and 5-FU chemoresistance in CRC cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: CRC patients; Homo Sapiens
• Experiment for Molecule Alteration: Immunohistochemical (IHC) staining
• Experiment for Drug Resistance: Overall survival assay (OS)
• Mechanism Description: This study has demonstrated that overexpression of ALDOB in CRC cells promotes lactagenesis by regulating PDK1 activation. The secreted lactate is then transported to neighboring cells and converted to pyruvate by lactate-induced LDHB, enhancing the ability of OXPHOS in terms of basal respiration and acting as a repressor of CEACAM6 expression. Consequently, ALDOB/lactate-mediated expression of CEACAM6 promotes cell proliferation and 5-FU chemoresistance in CRC cells.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: CRC patients; Homo Sapiens
• Experiment for Molecule Alteration: Immunohistochemical (IHC) staining
• Experiment for Drug Resistance: Overall survival assay (OS)
• Mechanism Description: This study has demonstrated that overexpression of ALDOB in CRC cells promotes lactagenesis by regulating PDK1 activation. The secreted lactate is then transported to neighboring cells and converted to pyruvate by lactate-induced LDHB, enhancing the ability of OXPHOS in terms of basal respiration and acting as a repressor of CEACAM6 expression. Consequently, ALDOB/lactate-mediated expression of CEACAM6 promotes cell proliferation and 6-FU chemoresistance in CRC cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Oxaliplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: CRC patients; Homo Sapiens
• Experiment for Molecule Alteration: Immunohistochemical (IHC) staining
• Experiment for Drug Resistance: Overall survival assay (OS)
• Mechanism Description: This study has demonstrated that overexpression of ALDOB in CRC cells promotes lactagenesis by regulating PDK1 activation. The secreted lactate is then transported to neighboring cells and converted to pyruvate by lactate-induced LDHB, enhancing the ability of OXPHOS in terms of basal respiration and acting as a repressor of CEACAM6 expression. Consequently, ALDOB/lactate-mediated expression of CEACAM6 promotes cell proliferation and 6-FU chemoresistance in CRC cells.

References

• Ref 1: Aldolase B-driven lactagenesis and CEACAM6 activation promote cell renewal and chemoresistance in colorectal cancer through the Warburg effect. Cell Death Dis. 2023 Oct 10;14(10):660.