Surprising findings by Queen’s researchers have shed new light on how
the "sunshine vitamin" D – increasingly used to treat and prevent
cancer and other diseases – is broken down by our bodies.
effectiveness of vitamin D therapy is partly dependent on how quickly
it will be broken down," says Biochemistry professor Glenville Jones,
an expert in the field of vitamin D metabolism. "By studying the enzyme
responsible for breaking down the vitamin, we hope to develop a way to
prevent this from happening by blocking that response."
First observed in Dr. Jones’s lab by undergraduate Biochemistry student
Brendan O’Leary, the discovery reveals that changing a single amino
acid in the hydroxylase enzyme will cause it to take a completely
different pathway. Although scientists have known for 25 years that the
enzyme is capable of taking two different pathways, until now they
could not explain why this occurs.
The team’s findings are
published on-line in the journal Proceedings of the National Academy of
Sciences (PNAS). Other members include: research associate David
Prosser, PhD student Martin Kaufmann, and research technician Valarie
Earlier study of the enzyme had shown that its pathway
pattern is species specific. Some species, including humans and rats,
favour one pathway, while others – most notably the opossum – favour
the other pathway.
Using a technique called liquid
chromatography mass spectrometry, the researchers studied cells from
animals in both categories. They changed the human enzyme in certain
key places to see if this would affect its pathway pattern.
they discovered that altering a single amino acid completely changes
the enzyme from a human pattern to an opossum pattern. This change can
be flicked back and forth "like a light switch," says Dr. Jones,
adding: "It’s remarkable. In biochemistry you rarely see that kind of
predictive work from modeling molecules and enzymes."
Queen’s researchers believe the hydroxylase enzyme plays an important
role in human cell functions. When vitamin D drugs are used in an
attempt to arrest certain types of cancer, for example, the tumour
responds by making more of this enzyme. "If we can block the tumour
response, we should be able to successfully treat some tumours with
vitamin D compounds," says Dr. Jones, whose research is supported by
the Canadian Institutes of Health Research.
Vitamin D deficiency
has also been correlated with other diseases, including multiple
sclerosis, muscle weakness, and bone-related disorders, he notes.
Queen’s University. June 2007.