Vitamin D and Evolution
Vitamin D is an accident or miracle of evolution. The process is in some respects quite simple. It starts with a long chain fatty acid called squalene, first discovered as shark oil in 1916. It is related to the omega group of fatty acids.
Squalene
Metabolic processes bend the molecule into a four-ring structure, ultimately becoming the important molecule 4-dehydrocholesterol (4-DHC). These processes are fundamental to life as simple fatty acids are the building blocks of cell structures, especially cell walls. Importantly, 4-DHC is synthesised by plankton, simple organisms living in the sea, close to the surface.
7-Dehydrocholesterol (7-DHC)
Now comes the real miracle. Ultraviolet light from the sun, particularly the wavelengths UVB 290-315nm, acts directly on the 7-DHC molecule and breaks one particular inter-atomic bond, shown in the diagram. This is not a biochemical process but is a physical process. It will occur in a test-tube containing 7-DHC just as well as in a living organism. The new molecule thus formed is called Pre-Vitamin D. It’s structure is unstable and it immediately unfolds to form vitamin D, Cholecalciferol. At this point the process is within plankton. But plankton are eaten by small fish, and then small fish are eaten by large fish. We consume large fish and thereby we consume vitamin D.
Pre-Vitamin D
Vitamin D (cholecalciferol)
Evolution led initially to single cell organisms with the ability to synthesise 7-DHC and thereby with the help of the sun, Vitamin D. Single cells then aggregated to multicellular organisms, ultimately leading to human beings. Our cells retain the ability to synthesise 7-DHC, and this includes the cells of the skin. The sun acting on the skin converts 7-DHC into vitamin D as cholecalciferol. We do not need to consume fish to obtain vitamin D, but only of we have adequate exposure to the sun at an adequate energy level. 7-DHC does not appear to have a metabolic function of its own, but it just a substrate for the synthesis of vitamin and also cholesterol. I am not aware that either 7-DHC or vitamin D confer any advantage on plankton, but it is likely that vitamin D synthesised within plankton enabled a further evolutionary development. Vitamin D is a pre-hormone and it appears to have very little activity in higher life forms such as mammals. It needs to be activated, and this required an evolutionary step. Vitamin D has one hydroxyl (-OH) group. The first evolutionary step was the creation of a liver enzyme which adds a second hydroxyl group, creating 25-hydroxy vitamin D (25-OH-Vit D). This is more simply called calcidiol. It has significant biological activity, but the kidneys also became capable of adding a third hydroxyl group, to create 1,25-dihydroxy vitamin D (1,25-OH VitD), also known as calcitriol. This has profound activity and a variety of functions.
Another essential step in evolution was the appearance of
vitamin D receptors (VDRs) within the cells. These perform essential functions in a variety of cells, but only when they are activated by vitamin D in its most active form of calcitriol, a hormone or messenger. The final step in evolution was a mechanism for inactivating calcitriol to prevent excessive activity. This required an additional enzyme in the liver to add a fourth hydroxyl group. The metabolism is thereby closely controlled. These evolutionary steps led to the ability of animal to have bones, obviously of immense importance and a development much earlier than homo sapiens and mammals in general. But vitamin D has functions other than the creation of bone, These are only just being appreciated, but most important is the enhancement of immunity. It is this that protects us from infections, and the one first understood was tuberculosis.
Tuberculosis affects those immuno-suppressed because of
vitamin D deficiency, occurring in particular in the winter, and in people with pigmented skins living in north European cities. AIDS is an important but less common cause of immuno-supression leading to tuberculosis. Vitamin D protects against other disease common in north-west Europe and North America, such as coronary heart disease, several cancers, and multiple sclerosis. These conditions might also be caused by chronic infections,
vitamin D deficiency giving susceptibility.
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