5th February 2024

Carbohydrate metabolism

Processes

Carbohydrates form a significant portion of the human diet and nutrition. This comprises three principal monosaccharides: glucose, fructose, and galactose. Glycogen is the storage form of carbohydrates in humans. 

In carbohydrate metabolism, one needs to understand:

Glycolysis

Glycolysis is a metabolic pathway catalysed by enzymes to convert glucose into pyruvate.

Gluconeogenesis

Gluconeogenesis results in the generation of glucose from non-carbohydrate sources that can be converted to pyruvate or intermediates of glycolysis. 

Glycogenolysis

This refers to the breakdown of glycogen into glucose-1-phosphate and then to glucose-6-phosphate, an intermediate in the glycolysis pathway. 

Glycogenesis

This refers to the process of synthesising glycogen. The glucose-6-phosphate (G6P) is the input substance for glycogenesis, created from glucose by glucokinase or hexokinase. 

Galactose metabolism

The main pathway is the Leloir pathway, which converts beta-D-galactose to alpha-D-galactose and using galactokinase enzyme to galactose-1-phosphate, then to UDP-glucose using galactose-1-phosphate uridylytransferase.

Image Source: Wikimedia Commons (2013). Galactose metabolic pathway, Licensed under a creative commons licence. Available for free at: https://upload.wikimedia.org/wikipedia/commons/f/fd/Galactose_metabolic_pathway.png (Accessed: 21 December 2023).

Disorders of carbohydrate metabolism

Disorders of carbohydrate metabolism can occur in many forms, and they can be divided mainly into acquired or inherited (inborn). 

Acquired

Acquired forms of carbohydrate metabolism are more common, including diabetic ketoacidosis, hyperosmolar hyperglycaemic state and hypoglycaemia. 

Inherited

This section aims to describe common to rare inborn carbohydrate metabolism disorders. These conditions are usually present in children, and understanding the metabolic pathway affected is vital to understanding these conditions. Many of the clinical features of the inherited disorders of carbohydrate metabolism are caused by:

• Lack of glucose for body organ metabolism
• Inability to break down glucose to pyruvate
• Inability to oxidise pyruvate fully in the Krebs cycle

For the MRCP Part 1 exam, it is beneficial to know some (rare) disorders of carbohydrate metabolism (and its associated high-yield facts), which are favourites. 

Galactosaemia

Galactosaemia is a rare autosomal recessive condition due to the deficiency of galactose-1-phosphate uridylyltransferase, resulting in the accumulation of galactose-1-phosphate. This causes features such as:

• Jaundice and hepatomegaly
• Failure to thrive
• (Oil droplet) cataracts
• Hypoglycaemia after exposure to galactose
• Fanconi syndrome

Galactokinase deficiency

Galactokinase deficiency is an autosomal recessive disorder causing decreased conversion of galactose to galactose-1-phosphate. Galactokinase catalyses the first step of galactose phosphorylation in the Leloir pathway, and patients do not present with severe manifestations in early infancy. Important features include cataracts. Diet is the foundation of therapy, with the elimination of lactose and galactose sources being the definitive therapy.

References

• Dixon M, MacDonald A, Stafford J, Portnoi P. Disorders of carbohydrate metabolism. Clinical paediatric dietetics. 2014 Nov 7:526-87.
• DiMauro S, Akman O, Hays AP. Disorders of carbohydrate metabolism. Handbook of clinical neurology. 2007 Jan 1;86:167-82.
• Dickens F, Whelan WJ, Randle PJ, editors. Carbohydrate Metabolism: And Its Disorders. Elsevier; 2014 May 12.
• Werny D, Taplin C, Bennett JT, Pihoker C. Disorders of Carbohydrate Metabolism. InAvery’s Diseases of the Newborn 2018 Jan 1 (pp. 1403–1416). Elsevier.