12.6 Vitamin A

Vitamin A

There are 3 forms of vitamin A (retinol, retinal, and retinoic acid) that collectively are known as retinoids. Retinol is the alcohol (OH) form, retinal is the aldehyde (COH) form, and retinoic acid is the carboxylic acid (COOH) form, as shown in the figure below (areas of difference are indicated by red)

Figure 12.61 Structure of the retinoids1

For more information on vitamin K, see the Required Web Link below.

Required Web LinkVitamin A Fact Sheet for Health Professionals

Subsections:

• 12.61 Carotenoids
• 12.62 Vitamin A Uptake, Absorption, Transport & Storage
• 12.63 Vitamin A Functions
• 12.64 Vitamin A Deficiency & Toxicity

References & Links

• Structures from Pubchem http://pubchem.ncbi.nlm.nih.gov/
• http://en.wikipedia.org/wiki/File:Retinyl_palmitate.png

Links

Vitamin A Fact Sheet for Health Professionals – https://ods.od.nih.gov/factsheets/VitaminA- HealthProfessional/

Carotenoids

Carotenoids are 40-carbon compounds that are found throughout nature. Animals do not produce carotenoids, thus any found in animals came from consumed plants or microorganisms. There are more than 600 natural carotenoids. However, the 6 main ones found in the diet and in the body are1: Beta-carotene, Alpha-carotene, Beta-cryptoxanthin, Lutein, Zeaxanthin, and Lycopene.

Many carotenoids are pigments, meaning they are colored. The table below gives the color of some of these carotenoids, as well as some food sources.

Table 12.611 Carotenoids’ color and food sources

Carotenoids can be further classified as provitamin A or non-provitamin A. Provitamin A carotenoids are those that can be cleaved to form retinal, while the non-provitamin A carotenoids cannot. After provitamin A carotenoids are taken up into the enterocyte, some are cleaved to form retinal. In the case of symmetrical beta-carotene, it is cleaved in the center to form 2 retinal molecules.

References & Links

1. Lindshield BL, Erdman JW. (2006) Carotenoids. In: Bowman BA, Russell RM, editors. Present Knowledge in Nutrition. Washington, D.C.: International Life Sciences Institute. pp. 184-197.r

Vitamin A Uptake, Absorption, Transport & Storage

The uptake, absorption, transport, and storage of vitamin A and carotenoids are summarized in the Figure 12.621.

Esters are removed by esterases so that free retinol can be taken up into the enterocyte. Preformed vitamin A is highly bioavailable (70-90%) if consumed with some fat2. Carotenoids

have a much lower bioavailability, which varies based on the carotenoid and matrix it is in when consumed. Once provitamin A carotenoids are taken up into the enterocytes, they are: (1) cleaved to retinal and then converted to retinol or (2) absorbed intact and incorporated into chylomicrons.

Figure 12.621 Vitamin A uptake, absorption, transport, and storage. Adapted from reference 1

Retinol in the enterocyte is esterified, forming retinyl esters. The retinyl esters are packaged into chylomicrons (CM) and enter the lymph system. Once the chylomicrons reach circulation, triglycerides are cleaved off to form chylomicron remnants (CM Rem). These are taken up by hepatocytes, where the retinyl esters are de-esterified to form retinol.

The liver is the major storage site of vitamin A. For storage, the retinol will be transported from the hepatocytes to the stellate cells and converted back to retinyl esters, the storage form of vitamin A. If vitamin A is needed to be released into circulation, retinol will combine with retinol binding protein (RBP). Retinol + RBP are then bound to a large transport protein, transthyretin (TTR). It is believed that retinol + RBP would be filtered out by the kidney and excreted in urine if it was not bound to TTR1.

After it is further metabolized, 60% of vitamin A is excreted in the urine, 40% in feces2.

References & Links

• Stipanuk MH. (2006) Biochemical, physiological, & molecular aspects of human nutrition. St. Louis, MO: Saunders Elsevier.Stipaunuk
• Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.

Vitamin A Functions

Vitamin A has a number of important functions in the body.

Vision

The retina is the inner back lining of the eye that takes visual images and turns them into nerve signals that are sent to the brain to form the images that we “see”, as shown in the following link1.

Web LinkRetina

Cell Differentiation

Vitamin A, in particular retinoic acid, is important for cell differentiation, or the ability of stem cells to develop into specialized cells.

References & Links

1. Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s perspectives in nutrition. New York, NY: McGraw-Hill.

Links

Retina – http://webvision.umh.es/webvision/imageswv/Sagschem.jpeg

Vitamin A Deficiency & Toxicity

Vitamin A deficiency is rare in North America, but is a huge problem in developing countries. In many developing countries, they do not have a stable dietary source of retinoids or provitamin.

Often the earliest symptom of vitamin A deficiency is night blindness, due to the insufficient production of rhodopsin. The reason that this is the earliest symptom, is that circulating vitamin A levels are homeostatically-controlled, meaning that they do not change until after vitamin A

stores are exhausted. This means that blood, serum, plasma measurements are going to appear normal until all stores are exhausted. As a result, sensitively assessing someone as vitamin A deficient can be challenging. There are further changes to the eye that occur during vitamin A deficiency, collectively referred to as xerophthalmia, which are shown in the Required Web Link on the next page.

Required Web LinkThe eye signs of vitamin A deficiency

Ultimately the person can become blind. Vitamin A deficiency is the leading cause of blindness in some parts of the world1.

Another symptom of vitamin A deficiency is hyperkeratosis. In this condition, cells overproduce the protein keratin, causing the skin to become rough and irritated, as shown in the link below1.

Required Web LinkHyperkeratosis

One way to counter vitamin A deficiency in developing countries is for staple crops, like rice and corn, to contain beta-carotene. In the case of rice, Golden Rice was genetically modified to produce beta-carotene. A second generation of golden rice, known as Golden Rice 2, has now been developed. However, politics and regulations have prevented it from being used. This is described in the first link. The second link shows some of the opposition to Golden Rice. The third is a nice figure that details the progress towards Golden Rice being used.

Required Web LinksGolden RiceThe Golden Rice – An exercise in how not to do science Golden Rice Project

Vitamin A can be very toxic and can cause serious symptoms, such as blurred vision, liver abnormalities, skin disorders, and joint pain1,2. In addition, research has suggested that people who consume high levels of vitamin A are more prone to bone fractures2. Toxic levels of vitamin A are also teratogenic, which means they could cause birth defects.

References & Links

• McGuire M, Beerman KA. (2011) Nutritional sciences: From fundamentals to food. Belmont, CA: Wadsworth Cengage Learning.
• Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s perspectives in nutrition. New York, NY: McGraw-Hill.

Links

The eye signs of vitamin A deficiency – http://www.cehjournal.org/article/the-eye-signs-of- vitamin-a-deficiency/

Hyperkeratosis – http://api.ning.com/files/pKcbIy8a8fSwvjlw-NqcoyW- h1U9xsjxM86*Pg7xe7WAS91frtrQFThTH2oDWcMvbUJ9Mlutd3B9tXk8hjbfmXkeZyJs- 7Mi/follicularhyperkeratosis1.jpg

Golden Rice – http://www.goldenrice.org/

The Golden Rice – An exercise in how not to do science – http://www.i-sis.org.uk/rice.php Golden Rice Project – http://www.irri.org/images/golden_rice/GoldenRiceProjectTimelineAugust2013.jpg