MadSci Network: Biochemistry
Query:

Re: How could you determine the role of an 'unknown' vitamin/mineral/nutrient?

Date: Sat Sep 30 05:03:19 2006
Posted By: Neil Saunders, Computational biologist
Area of science: Biochemistry
ID: 1153947631.Bc
Message:

hi Jessica,

Thanks for your question. First, let's define the 3 terms that you use: vitamin, mineral and nutrient. A nutrient can be defined as any element or compound obtained from the environment (e.g. in the diet) that an organism requires for metabolism. There's no hard and fast classification scheme for nutrients but if we think about them chemically, they fall into 5 major groups: carbohydrates, proteins, fats, vitamins and minerals. Sometimes you will also see water classed as a nutrient. This simplifies your question a little - vitamins and minerals are nutrients, so we only need to discuss those two terms further.

Dietary minerals are essentially elements, normally present in the diet in ionic form as salts. They can be divided into bulk - those required in larger amounts such as calcium, potassium and phosphorus and trace - required in smaller amounts, e.g. zinc, selenium and molybdenum.

Vitamins are organic molecules that normally act as cofactors or coenzymes - i.e. they are bound to enzymes which need them to catalyse reactions. Vitamins are frequently divided into fat-soluble (e.g. vitamin A, retinol) and water-soluble, (e.g. vitamin C, ascorbic acid). Animals obtain most vitamins from their diet, but some are synthesised by microorganisms and one - vitamin D - is synthesised in our skin under the action on sunlight.

OK - now that we understand the chemical nature of vitamins and minerals, we can think about how we might define their roles. One simple way would be to prepare a defined diet which lacked the vitamin or mineral and observe the effect(s) on an organism fed with that diet. For microorganisms this is quite simple; provided that we can culture the microbe, we can prepare defined growth media lacking the nutrient. Of course, we might find that the microbe fails to grow, or grows only very slowly, but this tells us at least that the nutrient is essential.
We can do a similar experiment using plants, where changes due to the missing nutrient are easier to observe. Plant fertilisers are defined by their "NPK" content - nitrogen (as nitrate), phosphorus (as phosphate) and potassium, the 3 most important minerals for a plant. Plants that lack nitrogen exhibit yellowed, weak unhealthy leaves, lack of phosphorus stunts growth and fruit/flower development and lack of potassium produces weakened plants susceptible to cold and drought.

Early physiological experiments studied the effects of nutrient-poor diets in animals. It's considered unethical to experiment on ourselves but in fact a lot of what's known about vitamins and minerals comes from observing people with inadequate diets. In this way we have found that vitamin C deficiency causes scurvy, in which connective tissues are not properly formed. Similarly we know that a lack of vitamin D causes rickets, a skeletal malformation and inadequate vitamin B3, niacin, causes the condition pellagra. There are many such examples of medical conditions linked to nutrient deficiency.

So, we can isolate nutrients, define them chemically and get some idea of the general physiological processes in which they are involved. What we really want to do is trace the fate of a nutrient in an organism - see which tissues, cells and ultimately, molecules contain it. This means either (1) finding a physical/chemical property of the nutrient that we can use to detect it in cells (using e.g. chromatography or spectroscopy) or (2) being able to label the nutrient in some way so that we can detect it. Here are a couple of examples.

In the study plasma clearance and net uptake of alpha-tocopherol and low-density lipoprotein by tissues in WHHL and control rabbits, tritium (a radioactive isotope of hydrogen) is used to label tocopherol, vitamin E. This enabled the researchers to follow the molecule and conclude that there were several different ways in which tissues could take up vitamin E from lipoproteins in the bloodstream.
Here's a more complex study - biochemical evidence for the existence of thymidylate synthase in the obligate intracellular parasite Chlamydia trachomatis. In this work, the authors are looking for the activity of an enzyme named thymidylate synthase in a parasitic organism. Other enzymes of this type contain a cofactor which is derived from folate, vitamin B9. Using some elegant labelling techniques (again with tritium), they find evidence for a specific thymidylate synthase dependent on methylenetetrahydrofolic acid, the long name for folate.

I could quote you many more examples. However, I hope you can see from this discussion that the history of figuring out the roles of nutrients is very much the history of biological chemistry. It begins with basic physiological observations, then chemical identification, then the use of biophysical and biochemical methods to label and follow molecules in cells. Nowadays we would add genetic techniques to that list - for instance in microorganisms, we might be able to deduce biochemical pathways that use certain nutrients by examining genome sequences, many of which are now available. So I suggest that you consult your chemistry and biochemistry texts for more examples and ideas of how to figure out the role of nutrients.

Hope that helped with your question,
Neil


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