Principles of Biochemistry Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
The Citric Acid Cycle
The alternative pathway for the conversion of glucose into glucuronic and ascorbic acids

The alternative secondary pathway of Glucose Catabolism in animal Tissues yields two specialized products: D-glucuronate, which plays a crucial role in the detoxification and excretion of foreign Organic compounds, and L-ascorbic acid (Vitamin C) (Fig. 16-21). In this pathway, D-glucose-1-phosphate first reacts with UTP to form UDP-glucose. The glucose moiety of UDP-glucose then undergoes enzymatic dehydrogenation to yield UDP-D-glucuronate. This reaction serves as yet another example of the utilization of UDP derivatives as intermediates in the enzymatic transformation of sugars (Sec. 15.9). UDP-D-glucuronate facilitates the Detoxification of Various xenobiotics or drugs (such as phenol), thereby promoting their renal excretion (Fig. 16-21). Furthermore, UDP-glucuronate acts as a precursor for D-glucuronate residues in acidic Polysaccharides such as hyaluronic acid and heparin (Sec. 11.12).

D-glucuronate also Functions as an intermediate in The conversion of D-glucose into L-ascorbic acid. It is reduced by NADPH to a six-carbon sugar acid, L-gulonate, which is subsequently converted into the corresponding lactone. L-gulonolactone is then dehydrogenated to L-ascorbic acid, or vitamin C, through the action of the flavoprotein gulonolactone oxidase. This is the exact pathway by which L-ascorbate is synthesized in plants and in animals capable of endogenous vitamin C production. Humans, guinea pigs, primates, certain bird species, and the Indian fruit bat cannot synthesize vitamin C; these species must obtain it preformed in their diet. Humans, guinea pigs, and various primates are unable to synthesize vitamin C because they lack the enzyme gulonolactone oxidase. It is likely that all organisms once possessed the full Complement of Enzymes required for ascorbate synthesis, but some species subsequently lost this biosynthetic capability due to a mutation—a mutation that proved non-lethal because their habitual diets consisted of vitamin C-rich plants.

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Fig. 16-21. The alternative pathway of glucose METABOLISM via UDP-glucuronic acid.

The fraction of glucose shunted into this secondary pathway is very small compared to the vast amounts degraded via Glycolysis and The Citric Acid Cycle. Nevertheless, the products of such alternative pathways are vital to the Organism.