Fructose-1,6-bisphosphate aldolase

Fructose-1,6-bisphosphate aldolase (FBA)

Fructose-1,6-bisphosphate aldolase (Aldolase; FBA) is a conserved metabolic enzyme that catalyzes the reversible cleavage of fructose-1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate during glycolysis and gluconeogenesis, thereby establishing it as a central regulator of cellular energy metabolism. Vertebrates express three major isoenzymes—Aldolase A (muscle and erythrocytes; ALDOA), Aldolase B (liver, kidney, and intestine; ALDOB), and Aldolase C (brain; ALDOC)-which exhibit distinct tissue distribution patterns yet possess highly conserved catalytic structures. Aldolase also performs non-canonical "moonlighting" functions, such as signal transduction, transcription, cytoskeletal organization, pathogen virulence, host cell adhesion, and immunomodulation. In Francisella novicida, Aldolase directly regulates the transcription of katG and rpoA, thereby linking metabolic signals to host redox regulation and inflammatory responses. In the field of oncology, the dysregulation of ALDOA, ALDOB, and ALDOC contributes to metabolic reprogramming, tumor proliferation, metastasis, and therapeutic resistance.
In prostate cancer, the overexpression of ALDOA promotes proliferation and tumor growth; conversely, the Aldolase A inhibitor naphthol AS-E phosphate suppresses cancer cell growth in a dose-dependent manner, thereby supporting the rationale for metabolism-targeted therapeutic strategies. In oral squamous cell carcinoma, ALDOC inhibits cell migration, invasion, ATP production, and lactate generation through its catalytic residues, Arg42 and Lys146, highlighting its subtype-specific functional relevance. In the realm of infectious diseases, given that mammals primarily express Class I aldolases, microbial Class II aldolases have emerged as promising targets for antimicrobial therapy. Structure-guided design has facilitated the development of zinc-chelating hydroxamate inhibitors that exhibit nanomolar potency and high selectivity for microbial Class II aldolases, providing lead compounds for the development of novel therapeutics against tuberculosis and other bacterial infections. In Mycobacterium tuberculosis, the deletion of FBA leads to bacterial clearance during both acute and chronic infection, validating its essentiality in vivo.

References:

[1]. Aldolase. Biochemistry, Genetics and Molecular Biology. Sciencedirect Topic.

[2]. Arakaki TL, et al. Structure of human brain fructose 1,6-(bis)phosphate aldolase: linking isozyme structure with function. Protein Sci. 2004 Dec;13(12):3077-84.

[3]. Pirovich DB, et al. Multifunctional Fructose 1,6-Bisphosphate Aldolase as a Therapeutic Target. Front Mol Biosci. 2021 Aug 11;8:719678.

[4]. Ziveri J, et al. The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella. Nat Commun. 2017 Oct 11;8(1):853.

[5]. Kuang Q, et al. The ALDOA Metabolism Pathway as a Potential Target for Regulation of Prostate Cancer Proliferation. Onco Targets Ther. 2021 May 24;14:3353-3366.

[6]. Li YJ, et al. Suppression of fructose-bisphosphate aldolase C expression as a predictor of advanced oral squamous cell carcinoma. Head Neck. 2016 Apr;38 Suppl 1:E1075-85.

[7]. Daher R, et al. Rational design, synthesis, and evaluation of new selective inhibitors of microbial class II (zinc dependent) fructose bis-phosphate aldolases. J Med Chem. 2010 Nov 11;53(21):7836-42.

[8]. Puckett S, et al. Inactivation of fructose-1,6-bisphosphate aldolase prevents optimal co-catabolism of glycolytic and gluconeogenic carbon substrates in Mycobacterium tuberculosis. PLoS Pathog. 2014 May 22;10(5):e1004144.

Fructose-1,6-bisphosphate aldolase Related Products (20):

By Effects:	Inhibitors (5) Substrates (6)

Cat. No.	Product Name	Effect	Purity	Chemical Structure

HY-148189

Aldometanib	Inhibitor	99.65%
Aldometanib (LXY-05-029) is an orally active aldolase inhibitor. Aldometanib can activate lysosomal adenosine monophosphate-activated protein kinase (AMPK) and decreases blood glucose. Aldometanib can be used for the research of metabolic homeostasis.

HY-W041994

GMBS		99.66%
GMBS is a heterobifunctional crosslinker targeting primary amines and sulfhydryl groups. GMBS can be used for chemical crosslinking of proteins and crosslinking mass spectrometry (CXMS) to study protein folding and map interfaces between interacting proteins.

HY-148077

Phosphoglycolohydroxamic acid	Inhibitor	98.0%
Phosphoglycolohydroxamic acid is a potent aldolase and triose-phosphate isomerase inhibitor. Phosphoglycolohydroxamic acid can be used in the research of antibacterial and antifungal area.

HY-P2726

Aldolase, Rabbit muscle	Substrate
Aldolase, Rabbit muscle (Fructose-diphosphate aldolase) is a glycolytic enzyme and glucose availability sensor. Aldolase, Rabbit muscle catalyzes the reversible carbon-carbon cleavage of fructose-1,6-bisphosphate to produce dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Aldolase, Rabbit muscle is an essential component for v-ATPase activity. Aldolase, Rabbit muscle participates in processes such as gluconeogenesis, the Calvin cycle and glycolysis.

HY-W012874

D-Threonine		99.40%
D-Threonine (H-D-Thr-OH) is one of the important unnatural amino acids used as chiral building blocks in pharmaceutical drugs. D-Threonine is a metabolite of Saccharomyces cerevisiae. D-Threonine is cleaved into glycine and acetaldehyde by the catalytic action of D-threonine aldolase.

HY-181267

ALDOA-IN-1	Inhibitor	98.46%
ALDOA-IN-1 is an aldolase A(ALDOA) inhibitor. ALDOA-IN-1 directly inhibits ALDOA enzymatic activity, thereby reducing lactate production, downregulating HIF-1α expression, and ultimately inducing cancer cell apoptosis. ALDOA-IN-1 can be used for research on colorectal cancer.

HY-E71071

(4S)-4-Hydroxy-2-oxoglutarate aldolase
(4S)-4-Hydroxy-2-oxoglutarate aldolase (EC 4.1.3.42) is specific for the (S) enantiomer.(4S)-4-Hydroxy-2-oxoglutarate aldolase (EC 4.1.3.42) catalyses the reactions of EC 4.1.1.3, oxaloacetate decarboxylase and EC 4.1.2.14, 2-dehydro-3-deoxy-phosphogluconate aldolase.

HY-E70975

3-Deoxy-D-manno-octulosonate Aldolase, E.coli
3-Deoxy-D-manno-octulosonate Aldolase, E. coli (EC 4.1.2.23) belongs to the aldehyde lyase family and is capable of cleaving carbon-carbon bonds. 3-Deoxy-D-manno-octulosonate Aldolase, E. coli (EC 4.1.2.23) has one substrate: 3-deoxy-D-mannooctulose, and two products: pyruvate and D-arabinose.

HY-143899

FBA-IN-1	Inhibitor	99.92%
FBA-IN-1 (compound 2a11) is a first-in-class, covalent and allosteric inhibitor of fructose-1,6-bisphosphate aldolase from Candida albicans (CaFBA). FBA-IN-1 inhibits the growth of Azole-resistant strains 103 with the MIC₈₀ of 1 μg/mL.

HY-N10374

Perseitol		99.82%
Perseitol is a heptoses produced by mature avocado plants. Perseitol can be converted to D-mannoheptulose as an energy-providing compound as well as a transport carbohydrate. Perseitol may act as a ripening inhibitor during the fruit ripening process. Perseitol’s synthesis may be related to the aldolase reaction in the Calvin cycle .

HY-147064

DL-4-Hydroxy-2-ketoglutarate lithium	Substrate
DL-4-Hydroxy-2-ketoglutarate lithium is the substrate of 4-hydroxy-2-oxoglutarate aldolase (HOGA). DL-4-Hydroxy-2-ketoglutarate lithium can be cleaved by HOGA to produce pyruvate and glyoxylate.

HY-N13363

2-Keto-3-deoxy-6-phosphogluconate	Substrate
2-keto-3-deoxy-6-phosphogluconate is an endogenous metabolite found in Escherichia coli, and a key intermediate in the Entner-Doudoroff (ED) pathway, as well as in the degradation pathways of sugar acids and sugar polymers in human and plant pathogens. It is produced by the catalytic action of KDPG aldolase.

HY-W012874S

D-Threonine-d₂	Substrate
D-Threonine-d₂ (H-D-Thr-OH-d₂) is the deuterium labeled D-Threonine (HY-W012874). D-Threonine is one of the important unnatural amino acids used as chiral building blocks in pharmaceutical drugs. D-Threonine is a metabolite of Saccharomyces cerevisiae. D-Threonine is cleaved into glycine and acetaldehyde by the catalytic action of D-threonine aldolase.

HY-P2977

N-Acetylneuraminate lyase (CgNal)
N-Acetylneuraminate lyase (CgNal) (Sialic acid aldolase (CgNal)) is a class I aldolase, is often used in biochemical studies. N-Acetylneuraminate lyase (CgNal) catalyzes the reversible condensation of pyruvate with N-acetyl-d-mannosamine (ManNAc) to yield the sialic acid N-acetylneuraminic acid (Neu5Ac).

HY-E70621

Sialic acid aldolase (Pm NaNa)
Sialic acid aldolase (Pm NaNa) (EC 4.1.3.3) is a type I aldolase that catalyze the reversible aldol cleavage of N-acetylneuraminic acid (Neu5Ac) to form pyruvate and N-acetyl-D-mannosamine (ManNAc) with the equilibrium favoring the Neu5Ac cleavage.

HY-E71030

Aldolase A, Human
Aldolase A, Human (EC 4.1.2.13) is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Aldolase A, Human (EC 4.1.2.13) , fused to His-tag at N-terminus, was expressed in E.coli.

HY-P2726A

Aldolase, Spinach
Aldolase, Spinach (EC 4.1.2.13) is an enzyme catalyzing a reversible reaction that splits the aldol, fructose 1,6-bisphosphate, into the triose phosphates dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). Aldolase, Spinach (EC 4.1.2.13) can also produce DHAP from other (3S,4R)-ketose 1-phosphates such as fructose 1-phosphate and sedoheptulose 1,7-bisphosphate.

HY-180388

Stibophen	Inhibitor
Stibophen is a potent antiparasitic agent is effective against Litomosoides carinii, Dipetalonema witei, and Brugia pahangi. Stibophen inhibits lactate accumulation and phosphofructokinases (PFK) activity in adult filariids. Stibophen also inhibits Ascaris and Hymenolepis diminuta PFK without inhibiting mammalian liver PFK. Stibophen can be used for the research of schistosomiasis and filariid infections.

HY-147064A

DL-4-Hydroxy-2-ketoglutarate	Substrate
DL-4-Hydroxy-2-ketoglutarate serves as a substrate for the enzymes GOT (glutamic oxalacetic aminotransferase) and 2-keto-4-hydroxyglutarate aldolase, facilitating the reversible breakdown of 2-keto-4-hydroxyglutarate into pyruvate and glyoxylate; it has also found applications in mass spectrometry for the swift analysis of negatively charged, water-soluble cellular metabolites.

HY-N10374R

Perseitol (Standard)	Substrate
Perseitol is a heptoses produced by mature avocado plants. Perseitol can be converted to D-mannoheptulose as an energy-providing compound as well as a transport carbohydrate. Perseitol may act as a ripening inhibitor during the fruit ripening process. Perseitol’s synthesis may be related to the aldolase reaction in the Calvin cycle .

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