THE REDUCTION OF l-XYLULOSE TO XYLITOL BY GUINEA PIG LIVER MITOCHONDRIA

Touster, Oscar; Reynolds, Vernon; Hutcheson, Ruth M.

doi:10.1016/s0021-9258(18)65182-8

Cited by 83 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The A. niger enzyme has a K m for L-xylulose of 17 mM (925 mM for xylitol, 0.03 mM for NADPH, and 0.13 mM for NADP) (17). Liver enzymes have K m values for L-xylulose of 0.29 mM (guinea pig) (18) and 0.26 mM (hamster liver) (24). The L-xylulose reductase from T. reesei has properties similar to those of the corresponding enzyme that was purified from A. niger.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Missing Link in the Fungal l-Arabinose Catabolic Pathway, Identification of the l-Xylulose Reductase Gene^,

et al. 2002

View full text Add to dashboard Cite

The fungal L-arabinose pathway consists of five enzymes, aldose reductase, L-arabinitol 4-dehydrogenase, L-xylulose reductase, xylitol dehydrogenase, and xylulokinase. All the genes encoding the enzymes of this pathway are known except for that of L-xylulose reductase (EC 1.1.1.10). We identified a gene encoding this enzyme from the filamentous fungus Trichoderma reesei (Hypocrea jecorina). The gene was named lxr1. It was overexpressed in the yeast Saccharomyces cerevisiae, and the enzyme activity was confirmed in a yeast cell extract. Overexpression of all enzymes of the L-arabinose pathway in S. cerevisiae led to growth of S. cerevisiae on L-arabinose; i.e., we could show that the pathway is active in a heterologous host. The lxr1 gene encoded a protein with 266 amino acids and a calculated molecular mass of 28 428 Da. The LXRI protein is an NADPH-specific reductase. It has activity with L-xylulose, D-xylulose, D-fructose, and L-sorbose. The highest affinity is toward L-xylulose (K(m) = 16 mM). In the reverse direction, we found activity with xylitol, D-arabinitol, D-mannitol, and D-sorbitol. It requires a bivalent cation for activity. It belongs to the protein family of short chain dehydrogenases. The enzyme is catalytically similar and homologous in sequence to a D-mannitol:NADP 2-dehydrogenase (EC 1.1.1.138).

show abstract

Section: Discussionmentioning

confidence: 99%

“…For molds, l -xylulose reductase was described for the filamentous fungi Penicilium chrysogenum () and Aspergillus niger (). For higher animals, l -xylulose reductase activity was found in guinea pig liver ( − ). A partly purified l -xylulose reductase from pigeon liver is commercially available (Sigma Aldrich).…”

Section: Discussionmentioning

confidence: 99%

The Missing Link in the Fungal l-Arabinose Catabolic Pathway, Identification of the l-Xylulose Reductase Gene^,

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Xylitol is natural, and humans are reported to produce approximately 15 g of xylitol per day in the liver [31]. Xylitol is converted by mitochondrial xylitol dehydrogenase into a precursor of the tricarboxylic acid cycle.…”

Section: Introductionmentioning

confidence: 99%

Cancer Cell Line Inhibition by Osmotic Pump-administered Xylitol in a Syngeneic Mouse Model

Cannon,

Dempsey,

Cosantino

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: This study aimed to evaluate the effects of continuous administration of xylitol (a commonly used dental prebiotic) via a subcutaneous osmotic minipump in a B16F10 syngeneic mouse model. Methods: The B16F10 syngeneic model consisted of 6–8-week-old C57BL/6 male mice subcutaneously injected with five × 105 B16F10 cells suspended in 100 μl PBS in the right flank. The mice were randomly assigned to two groups: Group 1 was the treatment group with 10% xylitol-loaded pumps (n=10), while Group 2 was the control group with saline-loaded pumps (n=10). Alzet minipumps were implanted subcutaneously in the left flank of B16F10-injected mice once more than 50% of all mice developed palpable tumors. After pump implantation surgery, the mice were monitored daily and weighed 2–3x/week. Tumor sizes were measured with calipers 2–3x/week, and all mice were euthanized when their tumors became too large (20 mm on any axis or 2,000 mm3). The excised tumors were weighed and cut in half, with one half sent for histology and the other for metabolomic analysis. Results: The xylitol-treated group survived substantially longer than the control group. The tumor size was reduced by approximately 35% by volume. Histological sections of xylitol treat mice suggested reduced infiltration and angiogenesis, which is consistent with previous studies. The metabolomic analysis demonstrates that xylitol reduces the tumor production of histamine, NADP+, ATP, and glutathione from the tumor, thereby improving the host immune response with ROS reactive oxygen species. Conclusions: The results of this study suggest that xylitol has potential as an adjunct to oncological treatment and is being further investigated in comparison to monoclonal antibody therapy (Opdualag).

show abstract

“…Interestingly, the typical human is reported to endogenously produce approximately 15 gm per day in the liver, making xylitol endogenous [26]. Indeed, xylitol is utilized by the mitochondria of cells as the precursor to the first step in the tricarboxylic acid cycle (also known as the citric acid cycle or the Krebs cycle), with xylitol dehydrogenase on the cristae converting xylitol to d-xylulose which then converts NADP to NADPH [27]. In addition to the liver production of xylitol, many plants, such as blueberries, strawberries, plums, cauliflower, and even oats, have substantial amounts of xylitol naturally present [28].…”

Section: Introductionmentioning

confidence: 99%

Effects of Xylitol on Tumor Progression in Syngeneic Mice Cancer Models

Cannon,

Cosantino,

Tesch

et al. 2024

Preprint

View full text Add to dashboard Cite

This study investigates the effects of xylitol, a natural sugar alcohol, on tumor progression in syngeneic mouse cancer models. Xylitol has been known for its dental health benefits, but emerging evidence suggests broader biological roles, including potential anti-cancer properties. We explored xylitol's impact on two mouse cancer models: 4T1 mammary carcinoma and B16F10 melanoma. Xylitol's efficacy in inhibiting cancer cell lines and modulating tumor progression was assessed using immunocompetent female mice. The experiments involved intratumoral and peri-tumoral administration of a 20% xylitol solution in two mouse strains: BALB/c (4T1 mammary carcinoma) and C57BL/6 (B16F10 melanoma). Tumor volume, histopathology, and metabolomic analyses were conducted to gauge xylitol's influence. The study revealed that xylitol administration initially reduced tumor growth in the B16F10 melanoma model, accompanied by alterations in tumor metabolism. However, similar effects were not observed in the 4T1 mammary carcinoma model, and melanoma tumor growth re-commenced after stroma deterioration permitted xylitol solution leakage. These findings suggest that xylitol may have potential as an adjunct therapy in cancer treatment, specifically in melanoma. The differential response between the two cancer models underscores the complexity of cancer biology and the need for further investigation into xylitol's mechanisms of action and its role in cancer therapy.

show abstract

THE REDUCTION OF l-XYLULOSE TO XYLITOL BY GUINEA PIG LIVER MITOCHONDRIA

Cited by 83 publications

References 28 publications

The Missing Link in the Fungal l-Arabinose Catabolic Pathway, Identification of the l-Xylulose Reductase Gene^,

The Missing Link in the Fungal l-Arabinose Catabolic Pathway, Identification of the l-Xylulose Reductase Gene^,

Cancer Cell Line Inhibition by Osmotic Pump-administered Xylitol in a Syngeneic Mouse Model

Effects of Xylitol on Tumor Progression in Syngeneic Mice Cancer Models

Contact Info

Product

Resources

About

THE REDUCTION OF l-XYLULOSE TO XYLITOL BY GUINEA PIG LIVER MITOCHONDRIA

Cited by 83 publications

References 28 publications

The Missing Link in the Fungal l-Arabinose Catabolic Pathway, Identification of the l-Xylulose Reductase Gene,

The Missing Link in the Fungal l-Arabinose Catabolic Pathway, Identification of the l-Xylulose Reductase Gene,

Cancer Cell Line Inhibition by Osmotic Pump-administered Xylitol in a Syngeneic Mouse Model

Effects of Xylitol on Tumor Progression in Syngeneic Mice Cancer Models

Contact Info

Product

Resources

About

The Missing Link in the Fungal l-Arabinose Catabolic Pathway, Identification of the l-Xylulose Reductase Gene^,

The Missing Link in the Fungal l-Arabinose Catabolic Pathway, Identification of the l-Xylulose Reductase Gene^,