Metabolic control analysis as a strategy to identify therapeutic targets, the case of cancer glycolysis

Marín‐Hernández, Álvaro; Saavedra, Emma

doi:10.1016/j.biosystems.2023.104986

Cited by 4 publications

(4 citation statements)

References 70 publications

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“…Among these, the mixed solution of Na 3 PO 4 -ACN demonstrated the most effective desorption of SPx. Then, the effect of different concentrations of Na 3 PO 4 -ACN (1,4,7,10,20,30, and 50 mM) on the desorption was examined (Figure S2g). Experimental results suggested that the highest desorption rate was achieved at a concentration of 7 mM.…”

Section: Evaluating the Enrichment Performance Of Hp-mentioning

confidence: 99%

“…Additionally, SPx are involved in DNA synthesis and complex cellular signaling networks. Some studies have shown that abnormal levels of SPx were closely associated with diseases such as cancer, metabolic disorders, and neurological conditions. − It is reported that fructose-1,6-bisphosphate was abundant in cancer cells but relatively low in normal cells, , and prostate cancer patients exhibit significantly elevated levels of fructose 6-phosphate, glyceraldehyde 3-phosphate, and dihydroxyacetone phosphate . Therefore, understanding the expression of SPx in physiological and pathological states is essential for insights into disease mechanisms and can guide diagnosis and treatment.…”

Section: Introductionmentioning

confidence: 99%

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Highly Defective Zirconium-Based Metal–Organic Frameworks for the Efficient Adsorption and Detection of Sugar Phosphates in the Biological Sample

Feng,

Hu,

Wang

et al. 2024

ACS Appl. Mater. Interfaces

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Enrichment and quantification of sugar phosphates (SPx) in biological samples were of great significance in biological medicine. In this work, a series of zirconium-based metal−organic frameworks (MOFs) with different degrees of defects, namely, HP-UiO-66-NH 2 -X, were synthesized using acetic acid as a modulator and were utilized as high-capacity adsorbents for the adsorption of SPx in biological samples. The results indicated that the addition of acetic acid altered the morphology of HP-UiO-66-NH 2 -X, with corresponding changes in pore size (3.99−9.28 nm) and specific surface area (894.44−1142.50 m 2 •g −1 ). HP-UiO-66-NH 2 -10 showed the outstanding performance by achieving complete adsorption of all four SPx using only 80 μg of the adsorbent. The excellent adsorption efficiency of HP-UiO-66-NH 2 -10 was also obtained with a wide pH range and short adsorption time (10 min). Adsorption experiments demonstrated that the adsorption process involved chemical adsorption and multilayer adsorption. By utilizing X-ray photoelectron spectroscopy and density functional theory to explain the adsorption mechanism, it was found that various interactions (including coordination, hydrogen bonding, and electrostatic interactions) collectively contributed to the exceptional adsorption capability of HP-UiO-66-NH 2 -10. Those results indicated that the defect strategy not only increased the specific surface area and pore size, providing additional adsorption sites, but also reduced the adsorption energy between HP-UiO-66-NH 2 -10 and SPx. Moreover, HP-UiO-66-NH 2 -10 showed a low limit of detection (0.001−0.01 ng•mL −1 ), high precision (<13.77%), and accuracy (80.10−111.83%) in serum, liver, and cells, good stability, high selectivity (SPx/glucose, 1:100 molar ratio), and high adsorption capacity (292 mg•g −1 for SPx). The practical detection of SPx from human serum was also verified, prefiguring the great potentials of defective zirconium-based MOFs for the enrichment and detection of SPx in the biological medicine.

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Section: Evaluating the Enrichment Performance Of Hp-mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Highly Defective Zirconium-Based Metal–Organic Frameworks for the Efficient Adsorption and Detection of Sugar Phosphates in the Biological Sample

Feng,

Hu,

Wang

et al. 2024

ACS Appl. Mater. Interfaces

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“…Since lactate dehydrogenase is essential for the Warburg effect (see below), it has also been explored as a therapeutic target with molecules such as GSK 2837808A [ 52 , 53 ]. Further, kinetic modeling and metabolic control analysis identified hexose-6-phosphate isomerase as a possible target in cancer [ 54 ]. This enzyme exerts high control in cancer glycolytic flux but not in normal cells.…”

Section: Cancer Treatmentmentioning

confidence: 99%

“…Consequently, in cells where glycolysis is essential as a source of energy and metabolites, this condition could seriously threaten the survival of such cells. Moreover, increased DHAP also inhibits hexose-6-phosphate isomerase [ 82 ], which in turn highly affects the glycolytic flux in cancer cells [ 54 ]. Therefore, based on the above arguments, HsTIM must be considered an attractive target for designing anticancer molecules [ 56 ].…”

Section: Triosephosphate Isomerase Is a Key Metabolic Enzymementioning

confidence: 99%

Human Triosephosphate Isomerase Is a Potential Target in Cancer Due to Commonly Occurring Post-Translational Modifications

Enríquez-Flores,

De la Mora-De la Mora,

García-Torres

et al. 2023

Molecules

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Cancer involves a series of diseases where cellular growth is not controlled. Cancer is a leading cause of death worldwide, and the burden of cancer incidence and mortality is rapidly growing, mainly in developing countries. Many drugs are currently used, from chemotherapeutic agents to immunotherapy, among others, along with organ transplantation. Treatments can cause severe side effects, including remission and progression of the disease with serious consequences. Increased glycolytic activity is characteristic of cancer cells. Triosephosphate isomerase is essential for net ATP production in the glycolytic pathway. Notably, some post-translational events have been described that occur in human triosephosphate isomerase in which functional and structural alterations are provoked. This is considered a window of opportunity, given the differences that may exist between cancer cells and their counterpart in normal cells concerning the glycolytic enzymes. Here, we provide elements that bring out the potential of triosephosphate isomerase, under post-translational modifications, to be considered an efficacious target for treating cancer.

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50 years of Metabolic Control Analysis: Its past and current influence in the biological sciences

Fell,

Saavedra,

Rohwer

2024

Biosystems

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Metabolic control analysis as a strategy to identify therapeutic targets, the case of cancer glycolysis

Cited by 4 publications

References 70 publications

Highly Defective Zirconium-Based Metal–Organic Frameworks for the Efficient Adsorption and Detection of Sugar Phosphates in the Biological Sample

Highly Defective Zirconium-Based Metal–Organic Frameworks for the Efficient Adsorption and Detection of Sugar Phosphates in the Biological Sample

Human Triosephosphate Isomerase Is a Potential Target in Cancer Due to Commonly Occurring Post-Translational Modifications

50 years of Metabolic Control Analysis: Its past and current influence in the biological sciences

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