Biological and Pharmacological Potential of Xylitol: A Molecular Insight of Unique Metabolism

Abstract

Xylitol is a white crystalline, amorphous sugar alcohol and low-calorie sweetener. Xylitol prevents demineralization of teeth and bones, otitis media infection, respiratory tract infections, inflammation and cancer progression. NADPH generated in xylitol metabolism aid in the treatment of glucose-6-phosphate deficiency-associated hemolytic anemia. Moreover, it has a negligible effect on blood glucose and plasma insulin levels due to its unique metabolism. Its diverse applications in pharmaceuticals, cosmetics, food and polymer industries fueled its market growth and made it one of the top 12 bio-products. Recently, xylitol has also been used as a drug carrier due to its high permeability and non-toxic nature. However, it become a challenge to fulfil the rapidly increasing market demand of xylitol. Xylitol is present in fruit and vegetables, but at very low concentrations, which is not adequate to satisfy the consumer demand. With the passage of time, other methods including chemical catalysis, microbial and enzymatic biotransformation, have also been developed for its large-scale production. Nevertheless, large scale production still suffers from high cost of production. In this review, we summarize some alternative approaches and recent advancements that significantly improve the yield and lower the cost of production.

Keywords: anti-cancer; anti-inflammatory; cardiovascular diseases; nutritive sweetener; respiratory tract infection; xylitol.

Figure 1

Generations of xylitol production from various substrate and catalytic agents. The journey began with the extraction of xylitol from wood (first generation) followed by catalytic reduction of xylose or xylose rich hydrolysate by metal catalysts (second generation). Bioprocessing, which uses photoautotrophic microorganisms developed/engineered to produce xylitol, predominates from the third generation onwards.

Figure 2

Xylose metabolism in (A) Xylitol non-producers and (B) Xylitol producer. Prokaryotes are able to oxidize xylose directly to xylulose in the presence of xylose isomerase (Pathway A) while in eukaryotes, this conversion proceeds with xylitol as an intermediate product (Pathway B).

Figure 3

Processing of lignocellulosic biomass for xylitol production. Agricultural residues are dried and grounded to obtain coarse powder, which is treated with chemical/biological reagents to obtain hemicellulosic hydrolysate. Microorganisms ferment the hydrolysate to various byproducts such as xylitol. After fermentation, broth is treated with activated charcoal and ion exchange resins to remove the contaminants, and xylitol crystals are obtained after lyophilization of clarified broth.

Figure 4

Metabolism of xylitol. Food and intracellular metabolism are two sources for xylitol. Xylitol consumed through food is referred to as exogenous xylitol and intracellularly-produced xylitol is endogenous xylitol. As shown in the figure, xylitol from both sources shares some common steps in metabolism.

Figure 5

Compensation of NADPH deficiency from xylitol metabolism by Hexose monophosphate to counter oxidative stress in glucose-6-phosphate deficiency induced hemolytic anemia. Due to glucose 6 phosphate deficiency, cells are unable to recover from oxidative stress due to a shortage of NADPH₂. Xylitol metabolism aid in generation of cofactor.