Vitamins A and D

Second last post for biochemistry! That was quick...

Understand the example roles given for retinol, retinal and retinoic acid

Vitamin A, just like some of the other vitamins that I've spoken about, is actually a range of related molecules. These include retinol, retinal, retinoic acid and carotenoids. The main structure consists of a β-ionone ring with a chain made up of isoprenoid units.

Carotenoids are known for giving things colour. They are stored in fat (remember, vitamins A, D, E and K are all fat-soluble) where they give fat its yellow colour. Carotenoids can even give birds their colour. If you eat too many carotenoids, your skin can become more orange, as I'll mention again later. Plants have another use for carotenoids: they are associated with photosystems and therefore play a role in light transduction.

Retinal is important for vision. Retinal bound to opsin (a G-protein coupled receptor that makes up part of the retina) is called rhodopsin. When light hits rhodopsin, rhodopsin can change from the cis- to the trans- conformation. Trans-rhodopsin can activate a G-protein called transducin, releasing opsin at the same time. If retinal is deficient, this can lead to xerophthalmia (a fancy term that just means "blindness").

Retinoic acid (RA) can affect gene transcription. RA can bind to the retinoic acid receptor (RAR), which usually exists as a heterodimer with the retinoid receptor (RXR). Usually, the RAR/RXR combo are usually bound to a co-repressor that blocks the retinoic acid response element (RARE). When RA binds to RAR, however, RAR and RXR can "de-repress" RARE, allowing gene transcription. Retinoic acid is involved in many signalling pathways, including MAPK and chemokine signalling pathways. It is also involved in guiding differentiation during embryonic development: a retinoic acid gradient forms along the length of the embryo due to metabolism by CYP450, which in turn can lead to different outcomes. (Fun fact: while CYP450 can break down RA, it can be re-built by retinaldehyde dehydrogenase.)

Vitamin A in mucus, infection and malnutrition

Mucus

Retinoic acid is important for triggering the creation of mucus-secreting goblet cells. It does not affect existing goblet cells, but when it's time for those cells to be replaced, you need retinoic acid or bad shit will happen. That bad shit, by the way, is replacement of goblet cells with squamous cells, causing squamous metaplasia.

Infection and malnutrition

Infection can deplete vitamin A for several reasons. Firstly, when you're sick, you may eat less, so you might not get enough vitamin A. Secondly, absorption might be impaired due to your illness. Excretion may also be increased due to diarrhoea or in urine. The problem with this is that, as I just said, low levels of retinoic acid can result in replacement of goblet cells with squamous cells. Fewer goblet cells means less mucus, and mucus normally helps to protect us from infection. It's a bit of a vicious cycle.

Know the daily requirements for vitamin A and disorders related to under and over supply

Okay, you know the drill:

• Children: 300-400 μg/day
• Teenagers: (Males) 600-900 μg/day (Females) 600-700 μg/day
• Adults: (Males) 900 μg/day (Females) 700 μg/day
• Lactation: 1 100 μg/day

Dietary sources include cod liver oil, liver, fortified cereals, fortified margarine and carrots. Too much retinol can be toxic. High levels of β-carotene are safe, but can turn your skin orange (though this is reversible).

Understand the creation and transformation of active vitamin D, its role in calcium resorption

Vitamin D, unlike other vitamins, can be created by us as long as we have sunlight. The starting point for vitamin D synthesis is 7-dehydrocholesterol which, as mentioned here, is also used to produce cholesterol. There are different forms of vitamin D: plants mainly have D2, whereas we mainly have D3. 7-dehydrocholesterol can be converted into pre-vitamin D3 via UV light, and pre-vitamin D3 can be converted into vitamin D3 via warmth.

But wait! It's not done yet. Vitamin D3 needs to undergo further activation. It needs to be hydroxylated into calcidiol and then hydroxylated again to form calcitriol, which is the active form of vitamin D3.

Calcitriol helps to regulate calcium levels in the body, along with parathyroid hormone (PTH). When calcium intake is low, the parathyroid gland releases PTH, which stimulates 1-hydroxylase. PTH and calcitriol can then stimulate osteoclasts, increasing the resorption of bone. This combination of PTH and calcitriol can also increase calcium resorption by the kidneys.

Know the daily requirements for vitamin D and disorders related to under and over supply

• Under 50s: 5 μg/day
• 50-70 years old: 10 μg/day
• Over 70s: 15 μg/day

As I've stated earlier, Vitamin D is kind of unique in that the majority of our intake is not through food: we produce it when we are exposed to sunlight. We become less efficient at producing it as we age, which is why older adults have a higher vitamin D requirement than younger adults. Foods that contain vitamin D include cod liver oil, fish, mushrooms and fortified foods. Extra supplementation might be needed for people who don't get adequate sunlight. Oversupplementation can lead to calcium build-up in the heart, lungs and kidneys, which isn't good. Low vitamin D, on the other hand, can lead to rickets and osteomalacia (see here).

Another point of interest is that since vitamin D can be found associated with a transcription factor (RXR), it may have other roles. In fact, some researchers are looking at possible relationships between vitamin D and cancer.