1

Celeste Peterson and Karly Krisovenski

Dr. Bartelson
SCH 202 01
27 November 2017

Vitamin A
In a world that is consumed by multivitamins or supplements, one would think that their
features and benefits would be well understood. However, this is not necessarily the case. On a
very broad level of understanding, a vitamin is any organic compound that a living organism
requires in small amounts, but cannot synthesize itself or cannot be produced by the body. There
are currently thirteen vitamins that are classified as either fat-soluble vitamins or water-soluble
vitamins. In general, fat-soluble vitamins are stored until they are needed by the body; because of
this, they are not as commonly ingested in our diets. On the contrary, water-soluble vitamins are
not stored in the body and therefore are regularly included in one’s diet. Both fat-soluble
vitamins and water-soluble vitamins play a large, varying role within the body, ranging from
supporting bone health to promoting normal brain function (3).
Vitamin A, in particular, is a fat soluble vitamin that was first discovered by scientist
Elmer McCullum (7). The term encompasses a group of compounds that includes provitamin A
carotenoids and retinol. Provitamin A carotenoids are found in foods from plants and some fruits
and vegetables. When they are first ingested, provitamin A carotenoids are not in the form of
vitamin A; they must be metabolized in the body. There are four types of provitamin A
carotenoids: alpha, beta, gamma, and cryptoxanthin. Out of these four, beta-carotene is the most
commonly encountered carotenoid with provitamin A activity in foods (4). The latter of the two
groups of compounds, retinol, is found in foods from animals, such as dairy products, liver, and
fish oils. It is already in the form of vitamin A and does not need to be metabolized into it the
way that carotenoids do.
Structurally, vitamin A is a 20 carbon unsaturated lipid molecule consisting of an alkene
functional group and an alcohol functional group. This can be seen in Figure 1 below. The
molecular formula of vitamin A is C20H3O and its molecular weight is 286.459 g/mol (10).
 2

Figure 1: Chemical Structure of Vitamin A (8)

In the body, there are three active forms of vitamin A: retinol, retinal, and retinoic acid,
which all are acquired from the foods that one consumes throughout the day (8). Overall, these
three active forms play vital roles in tissue differentiation, gene expression, immunity, growth,
and vision. In tissue differentiation and gene expression, retinoic acid acts as a molecule that
binds to receptors in the nucleus of cells, both somatic and visceral cells. These receptors bind to
specific regions on the DNA molecule to regulate the expression of various genes. With the help
of transcription factors that control the rate of transcription, or the process in which DNA is
copied to make RNA, certain genes are coded for and cell differentiation is controlled. For
example, nuclear receptors that are originally bound to retinoic acid in the gonads ultimately
increase gene expression and maintain reproductive tissues (4).
As is mentioned above, retinoic acid plays an important role in cell differentiation,
especially in white blood cells, or leukocytes, which are a vital component of the immune
system. White blood cells act in immunity by combating any foreign substance in the body that
can potentially lead to infection. Aside from aiding in the development of leukocytes themselves,
vitamin A and retinoic acid also maintain the stability and functionality of the skin and mucosal
cells; these cells act as the body’s first line of defense by forming barriers between the external
environment and the internal environment (4). This way, infections must overcome a physical
obstacle in order to invade the body. Furthermore, vitamin A and the most common provitamin
A carotenoid, beta-carotene, are found to be powerful antioxidants that neutralize and control
harmful free radicals in the body responsible for tissue and cellular damage (1). With this
restraint on cells, they are less likely to become overactive, especially when encountered with
food proteins. The hypersensitivity between the cells and food proteins is what creates food
allergies, which in turn causes inflammation. If there is more vitamin A or beta-carotene present,
the inflammatory response to certain food proteins is less likely to occur, preventing the
dangerous overreaction in the body.
 3

Not only does vitamin A serve a function in immunity, it also aids in growth, particularly
in regard to bone and brain development. Vitamin A helps in the development of the cells known
as osteoblasts, which are responsible for the synthesis and mineralization of bone (2). In relation
to the brain, the vitamin is a signaling molecule for neurogenesis, or the formation of neurons
from undifferentiated neural stem cells. In the development of the central nervous system during
gestation, retinoic acid is secreted by the meninges and taken up by the neural stem cells,
ultimately promoting neurogenesis. Aside from playing a role in embryonic development,
vitamin A continually affects the minor development of the brain in adults. While it might not
play as large of a role in adulthood, retinoic acid continues to stimulate neural stem cell
differentiation and contributes to neuroplasticity, or the brain’s ability to change form and
function in response to the surrounding environment (9).
Among the many functions and roles of vitamin A, its impact in relation to vision is
arguably the most important throughout the body. On a broader spectrum, retinal in the retina of
the eye binds to the light-sensitive proteins called opsins that contribute to the formation of
rhodopsin and iodopsin. These pigments are also known as the rod photoreceptors and the cone
photoreceptors, which are responsible for mediating vision in dim light and in bright light,
respectively. An electrical stimulus is generated from the photoreceptors and is sent to the optic
nerve, where a nerve impulse is created. The nerve impulse is then conveyed to the brain, where
it can be processed and integrated as vision (6).
The processing and integration of electrical stimuli to produce visual information is
understood as the visual cycle. The visual cycle begins with the detection of either dim or bright
light in the retina via the photoreceptor cells, rods and cones. In order to identify the presence of
light, the cells utilize the carotenoid 11-cis-retinal, which is a derivative of vitamin A. The 11-
cis-retinal covalently binds to the protein opsin, which when bound together form a visual
pigment that possesses the ability to absorb visual light. The 11-cis-retinal contributes to the
pigment by responding to light via a structural change, and the opsin portion of the pigment
determines the wavelength to which the pigment responds. When the light is finally
encountered, 11-cis-retinal experiences the structural change mentioned above. More
specifically, 11-cis-retinal undergoes an isomerization reaction to form all-trans-retinal, as is
depicted in Figure 2 below. Opsin is activated once the isomerization reaction occurs to convert
11-cis-retinal to all-trans-retinal.
 4

Figure 2: Isomerization of 11-cis retinal in the presence of light (5)

Once opsin is activated, it is released from the all-trans-retinal that was produced from the
isomerization reaction, and at this point, all-trans-retinal continues in the visual cycle. The all-
trans-retinal is then reduced to all-trans-retinol. The reduced all-trans-retinol then exits the
photoreceptor and enters the retinal pigment epithelium (RPE). Here, it is converted to all-trans-
retinyl ester through the linking of all-trans-retinol to phosphotidylcholine, which is a
phosphoglyceride found in membranes, via the enzyme lecithin retinol acyl transferase. The all-
trans-retinyl ester can either be stored in the RPE or can continue in the pathway to regenerate
11-cis-retinal. The retinyl esters that continue in the cycle are simultaneously hydrolyzed and
isomerized to form 11-cis-retinol, which is facilitated by a generically termed enzyme,
isomerohydrolase; the newly synthesized molecule can then be oxidized to 11-cis-retinal with the
help of 11-cis-retinol dehydrogenase as an enzyme and NAD+ as a cofactor. Once 11-cis-retinal
is regenerated, it is sent back to the rod cells, where it is needed to bind with opsin to restart the
cycle. Essentially, the visual cycle, which is depicted in Figure 3 below, constantly regenerates
11-cis-retinal in order promote the optimal functioning of opsin (5).

Figure 3: The Visual Cycle (5)

 5

In order to reap the various benefits of vitamin A, such as the visual cycle, it must be
consumed in the diet. The recommended daily allowance of vitamin A differs amongst age
groups, with infants and children and adolescents requiring the least amount per day.
Specifically, infants (0-12 months) are suggested to consume 400-500 micrograms per day, and
children and adolescents (1-18 years) are recommended anywhere from 300-900 micrograms per
day. In adulthood, men and women should consume 900 and 700 micrograms of vitamin A per
day, respectively (11). One can receive the adequate amount of vitamin A in the diet by
consuming foods such as liver, fish, kidney, eggs, and dark and deeply colored fruits and
vegetables. However, there is a possibility that vitamin A could be consumed too much, resulting
in disorders like acute toxicity, chronic hypervitaminosis, jaundice, cirrhosis, and portal
hypertension (10). Granted, it does take a great deal of vitamin A to reach this point; for
example, it would take approximately 309 eggs to do so!
While there are various different diseases or disorders that can progress due to an
overconsumption of vitamin A, the risks involved with an under consumption seem to be more
grave. When it comes to having the correct amount of vitamin A in the body, there are two
different aspects to consider: the way one’s body absorbs fat and the consumption of the vitamin
itself. First and foremost, if one has a condition that results in fat malabsorption, where the small
intestine does not absorb fat correctly, such as Celiac disease or Crohn’s disease, it is likely that
a vitamin A deficiency will develop in time. At first glance, it may seem strange that fat
absorption, or the lack thereof in these instances, would have an effect on vitamin A; however,
vitamin A is a fat-soluble vitamin and thus the absorption of it and other fat-soluble vitamins
depend on the same processes responsible for fat absorption (11). On the other hand, one may
not have a disease that impairs the processes involved in fat absorption. Instead, he or she simply
might not be consuming enough vitamin A, as it cannot be synthesized in the body. Regardless
of how the deficiency develops, there are a plethora of health problems that can arise as a result
of it.
As vitamin A, 11-cis-retinal specifically, plays a large role in the visual cycle, it is not
surprising that a vitamin A deficiency (VAD) can impair one’s sight, which is the largest
problem associated with a deficiency. VAD has been tied with some instances of total blindness,
but it is more commonly related to nyctalopia, or night blindness. Nyctalopia results from poor
adaptation to darkness, with the most noticeable symptom being difficulty seeing at night. There
 6

are various causes of nyctalopia, so in order to determine if VAD is the underlying cause, a
blood test must be performed. If the night blindness shows to be a result of a deficiency,
fortunately, there is a simple solution. Typically, a change in diet, with the inclusion of more
fruits and vegetables, will provide one that is deficient more than enough vitamin A; however, in
rare cases or in underdeveloped countries, where one’s diet does not have as much nutritional
value, a supplement of vitamin A may be necessary (12). Adding more vitamin A to the diet can
also boost immunity and hematopoiesis, but, as is mentioned above, ocular effects are the most
prominent problems associated with vitamin A deficiency (4).
Vitamin A is arguably one of the most important factors in various forms of development
within the body. Although vitamin A is only required in small amounts, compared to some other
vitamins, it does play a large role in many different parts of the body. Vitamin A has an effect on
cell differentiation, immunity, brain development, and vision, where it is the precursor for the
very important visual cycle. These are just a few of its current understood functions, and it is
likely that in time, more roles of vitamin A in relation to bodily processes will be discovered. All
in all, vitamin A, with its functions that are of the utmost importance, should be consumed every
day in order to promote physical and even mental health.
 7

References

(1) Axe, J., DNM, DC, CNS. Vitamin A: Benefits, Sources & Side Effects, 2017. Dr. Axe.
https://draxe.com/vitamin-a/ (accessed November 21, 2017).

(2) Brown, S., PhD. Key Vitamins for Bone Health ‒ Vitamin A, 2014. Better Bones.
https://www.betterbones.com/bone-nutrition/vitamin-a/ (accessed November 21, 2017).

(3) The Chemical Structures of Vitamins, 2015. Compound Interest.

http://www.compoundchem.com/2015/01/13/vitamins/ (accessed November 16, 2017).

(4) Chhabara, N., M.D. Vitamin A Chemistry, Functions and Deficiency, 2015. SlideShare.
https://www.slideshare.net/namarta28/vitamin-a-chemistry-functions-and-deficiency
(accessed November 16, 2017).

(5) Crouch, R. The Visual Cycle, 2009. Photobiological Sciences Online.

http://photobiology.info/Crouch.html (accessed November 21, 2017).

(6) The Editors of Encyclopædia Britannica. Rod, 2017. Encyclopædia Britannica.

https://www.britannica.com/science/rod-retinal-cell (accessed November 21, 2017).

(7) Frydman, C. Dietary Vitamin A: Which Form Should I Consume?, 2017. The Radiant
Life Blog. https://blog.radiantlifecatalog.com/dietary-vitamin-a-which-form-should-i-
consume (accessed October 22, 2017).

(8) Higdon, J., PhD. Vitamin A, 2015. Oregon State University.

http://lpi.oregonstate.edu/mic/vitamins/vitamin-A (accessed October 22, 2017).

(9) Oyarce, K.; Nualart, F. Unconventional Neurogenic Niches and Neurogenesis

Modulation by Vitamins, 2014. Journal of Stem Cell Research & Therapy.
https://www.omicsonline.org/open-access/unconventional-neurogenic-niches-
 8

neurogenesis-modulation-vitamins-2157-7633.1000184.pdf (accessed November 21,

2017).

(10) Retinol, 2017. PubChem.

https://pubchem.ncbi.nlm.nih.gov/compound/retinol#section=Top (accessed November
21, 2017)

(11) Second National Report on Biochemical Indicators of Diet and Nutrition in the
U.S. Population. Center for Disease Control and Prevention.
https://www.cdc.gov/nutritionreport/pdf/Fat.pdf (accessed October 22, 2017).

(12) Selner, M. What Causes Night Blindness?, 2016. Healthline.

https://www.healthline.com/symptom/night-blindness (accessed November 22, 2017).