Metabolism of glucuronic acid and its importance in the human body.

Glucuronic acid metabolism is primarily involved in detoxification, drug metabolism, and carbohydrate metabolism. It begins with the generation of UDP-glucose (Uridine diphosphate glucose), the same way glycogen metabolism begins. Then UDP-glucose acts as a a source for glucuronic acid.

Functions of Glucuronic Acid Metabolism:[edit | edit source]

Generates UDP-glucuronate which can be used for glycosaminoglycan synthesis (and proteoglycans), conjugate endogenous and exogenous substances.
Use L-gulonate to generate xylulose-5-phosphate which is part of the pentose cycle.
In plants and animals, can make ascorbic acid from L-gluconate.

Synthesis of UDP-Glucose (The source of Glucuronic Acid)[edit | edit source]

The generation of UDP-glucose begins with Glucose-6-phosphate. It is a two step process.
Glucose-6-phosphate is converted to glucose-1-phosphate by phosphoglucomutase.
A UTP molecule (high energy molecule) is attached to glucose-1-phosphate by UDP-glucose phosphorylase to generate UDP-glucose.
UDP-glucose can be used to generate glycogen or glucuronic acid.

UDP-Glucose Synthesis from glucose-6-phosphate.

Formation of Glucuronic Acid and its Fate in the body[edit | edit source]

UDP-glucuronic acid

The enzyme UDP-glucose 6-dehydrogenase catalyzes the conversion of UDP-glucose to UDP-glucuronic acid (UDPGA).

UDP-glucuronic acid is involved in conjugation of endogenous and exogenous compounds for excretion such as drugs, steroids, and bilirubin. It acts as a donor in the process of “glucuronidation” to make compounds more soluble. This is mediated by UDP-glucuronosyltransferase. A prime example is the conjugation of bilirubin in hepatocytes of the liver.
UDP-glucuronate can also be involved in synthesis of glycosaminoglycans (hyaluronic acid, chondroitin sulfate, dermatan sulfate) which is important for extracellular matrix structure.

Conjugation of bilirubin with glucuronic acid by UDP-glucuronosyltransferase (UGT).

Glucuronic acid can also be further converted to L-gulonate in a two-step process. L-gulonate can be converted to xylulose-5-phosphate, which is a part of the pentose phosphate pathway.

Resources[edit | edit source]

Literature[edit | edit source]

Abali. Lippincott Illustrated Reviews: Biochemistry. Wolters Kluwer, 2021.
Lieberman, Michael, and Alisa Peet. Marks’ Essentials of Medical Biochemistry: A Clinical Approach. Wolters Kluwer, 2015.