Biochemists reveal secret of vitamin D degradation

© Photographer: Norman Chan | Agency: Dreamstime.com

Biochemists at Queen’s University Canada have shed light on the way our bodies break down vitamin D.

It was already known that the hydroxylase enzyme accelerates a series of chemical reactions, known as a metabolic pathway, breaking down the vitamin. Two such pathways exist, but scientists did not understand why one is typically favoured over the other. The team discovered, however, that changing a single amino acid in this enzyme determines which pathway it will take.

Vitamin D based drugs are commonly used to treat and prevent cancer. The rapid degradation of the vitamin, though, limits the effectiveness of this form of therapy.

“By studying the enzyme responsible for breaking down the vitamin, we hope to develop a way to prevent this from happening,” said Dr Glenville Jones, who led the research.

Enzyme pathways

Scientists were aware that vitamin D can be broken down by two different enzyme pathways, with the choice of pathway being specific to certain species. Rats and humans, for instance, favour one pathway, whilst other animals, notable possums, favour the other.

"If we can block the tumour response, we should be able to successfully treat some tumours with vitamin D compounds.” Dr Glenville Jones

The research team used liquid chromatography mass spectrometry to compare cells from both types of animal. They then modified the human enzyme to see how this would affect its pathway.

The study revealed that changing a single amino acid in the hydroxylase enzyme causes it to take a completely different pathway. This change can be reversed and flicked back and forth ‘like a light switch’, said Dr Jones.

 ‘It’s remarkable. In biochemistry you rarely see that kind of predictive work from modelling,’ he added.

Tumours tend to respond to the use of vitamin D drugs by making more of the hydroxylase enzyme. The team therefore hope that their research could be used to improve the effectiveness of vitamin D cancer therapy.

‘If we can block the tumour response, we should be able to successfully treat some tumours with vitamin D compounds,” said Dr. Jones.

Vitamin D deficiency has also been correlated with other diseases, including multiple sclerosis, muscle weakness, and bone-related disorders.
 

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