Structural Biochemistry/Chemistry of important organic molecules in Biochemistry/Vitamins and Cofactors

From Wikibooks, open books for an open world
Jump to: navigation, search

Introduction to Vitamins[edit]

Vitamins are critical organic molecules necessary for life. Despite their vital importance, they cannot be synthesized by animals and they must be acquired through diet, whether they are obtained from food or through supplemental vitamins. This odd characteristic may have evolved because of the biological complexity of vitamin synthesis; it is more efficient to obtain vitamins in food in trace amounts than to develop the numerous enzymes necessary to synthesize vitamins. In addition, vitamins must be molecularly modified after ingestion before they can be used in the body. Vitamins can act ascoenzymes, signaling molecules, antioxidants, and hormones, as well as serving various other functions. Vitamin deficiency can lead to conditions such as: scurvy from lack of Vitamin C, and eye damage from lack of Vitamin A. In fact, many activated carriers in metabolism are derived from vitamins, including carriers important for redox reactions, such as electron transport (FADH2, for example), and carbon dioxide transfer (biotin). Because of the critical roles vitamins play in the functioning of the human body, they are an essential topic of study despite the low vitamin requirements of most animals.

Water-Soluble vs. Fat-Soluble[edit]

Approximately 14-20 vitamins have been discovered. There are two categories that vitamins fall under: water-soluble as well as fat-soluble.

Defined
Water-soluble: vitamins that easily dissolvable in water and easily excreted out of the body via urine output. As a result of this type of vitamin that can be dissolved in water, individuals cannot overdose on them because all excess will simply be excreted. Moreover, this type need to be replaced more on a regular basis. Some water-soluble vitamins are B vitamins(B1, B2, B3B6, B7, B12) and vitamin C.(1)

Fat-soluble: vitamins that are soluble in fat or lipids and are absorbed into the body through the intestinal tract or more specifically the small intestines.(1):
Some fat-soluble vitamins are vitamins A, D, E, and K.(1) Vitamins included in this category include vitamin A, vitamin D, vitamin E, as well as vitamin K. An acronym to help remember these fat-soluble vitamins- ADEK. Main areas in which fat-soluble vitamins are stored are the liver and adipose tissues. Fat-soluble vitamins except for vitamin K, are stored for long periods at a time and then excreted after this long duration of time has passed. For this reason overdosing on fat-soluble vitamins is highly feasible if ingested at high, toxic levels and it could possibly lead to hypervitaminosis.

Structure of Vitamins[edit]

Vitamin Structure
Vitamin A
Vitamin A.png
Vitamin B1 (Thiamin)
Thiamin.svg
Vitamin B2 (Riboflavin)
Riboflavin.svg
Vitamin B3 (Niacin)
Niacin structure.svg
Vitamin B5 (Pantothenic Acid)
Pantothenic acid.png
Vitamin B6 (Pyridoxine)
Pyridoxine structure ver2.svg
Vitamin B7 (Biotin)
Biotin structure JA.png
Vitamin B9 (Folic Acid)
Folicacid2.png
Vitamin B12 (Cobalamin)
Vitamin B12.png
Vitamin C
L-Ascorbic acid.svg
Vitamin D3 (Cholecalciferol)
Cholecalciferol-vitamin-D3-from-xtal-3D-sticks.png
Vitamin E
VitaminEstructure.png
Vitamin K
Vitamin K reduziert.svg

Functions of Vitamins[edit]

Vitamin A: is used for growing healthy new cells like skin, bones, and hair. Also is used for surface lining upkeep of the eyes, urinary tract, intestinal tract, and respiratory system. Night vision is also assisted by Vitamin A. Vitamin A also performs other major functions in the body. It is required for reproductive functions such as normal growth and development of sperm and ovaries. Vitamin A also helps vision by keeping cells which are used for transduction of light into nerve signals healthy. Vitamin can be found from certain foods such as egg yolk, whole milk, and butter.

Vitamin D: is needed for the body to properly use calcium and phosphorous. It is also used in the formation of some RNA, maintain a normal heart, keep a stable nervous system and blood clotting. Along with absorbing calcium, Vitamin D can also help regulate the amount of calcium and phosphorus that is present in the blood. Vitamin D can be found in dairy products, fish, and oysters. Vitamin D deficiency caused severe growth retardation. The lack of calcium in the bones resulted in deformities of the skeleton, characterized by a widening at the ends of the long bones because of a disorganization in the hypertrophy and maturation of chondrocytes in the epiphyseal plates. Vitamin D deficiency is also associated with a low-normal blood calcium, low or low-normal fasting blood phosphorus, and elevated parathyroid hormone (PTH) levels that cause a mineralization defect in the skeleton.


Vitamin E: is an antioxidant that helps the body get rid of free radicals to keep tissues healthy. It is also used in the creation of red blood cells. The use of vitamin A,C and K are assisted by Vitamin E. Although the role of Vitamin E is not completely understood but it is clear that it presents antioxidant properties in the body. They get rid of the free radicals in the body by preventing the oxidation of lipid-based cell membranes. Free radicals are very reactive and can steal electrons from membranes which could ultimately damage DNA. Good sources of Vitamin E are almonds, spinach, wheat, and asparagus. Of the many such dietary components, vitamin E has commanded most interest because of its availability, strong marketing potential, overall health impact, and central role in preventing oxidation at the cellular level.

Vitamin K: assists in creating proteins in the body like those that create blood clots. It also allows for calcium regulation within the body. Vitamin K’s ability to help the clotting of blood is important for healing. The clotting ability could help in slowing or stopping bleeding in injured patients. During surgery, Vitamin K is often given to patients to reduce bleeding. Sources of Vitamin K include spinach, Brussels sprouts, asparagus, and broccoli.

Vitamin B: are essential for creating dopamine, epinephrine, serotonin, and myelin. They also help the mind focus, help hemoglobin hold oxygen and lower cholesterol. Vitamin B is essential to good heath. It is also used for energy production in the human cells. B vitamins help convert food often consumed as carbohydrates into fuel. They also help the nervous system function properly. Good sources of Vitamin B are bananas, potatoes, whole grans, and chili peppers.

Vitamin C: helps regulate the immune system and relieve pain caused by tired muscles. It also is needed in the manufacture of collagen and norepinephrine. Vitamin C is also an antioxidant which can enhance the immune system by stimulating white blood cells in the body. Vitamin C also helps to benefit the skin, teeth, and bones. Vitamin C is often in citrus fruits such as papayas, oranges, and lemons.

The Different B Vitamins(4)

Vitamin B1:

Thiamin is another name for vitamin B1. It helps to convert blood sugar into energy for your body. It also helps the mucous membranes of the muscular, cardiovascular, and nervous systems in good shape. Some good sources of Vitamin B1 is from some whole grain cereals, pork, navy beans, and wheat germs.

Vitamin B2:

Riboflavin is another name for vitamin B2. It works with the other B vitamin complexes to process the carbohydrates, proteins, and fats into calories for energy in body. The body also needs this for healthy skin, good vision, growth, and red blood cell creation. Some good sources of Vitamin B2 is Dairy, red meats, and leafy green vegetables.

Vitamin B3:

Niacin is another name for vitamin B3. It also works with other B vitamin complexes to process the carbohydrates, proteins, and fats into calories for energy in the body. The difference is that it helps the digestive systems functions along with promoting a healthy appetite and healthy nerves. Large doses of niacin could lower LDL cholesterol but large doses is recommended to be taken under physician supervision. Some good sources of Vitamin B3 is yeasts, meat, and peanuts.

Vitamin B5:

Panththenic Acid is another name for vitamin B5. Like B3 and B2 it hlps break down carbohydrates, proteins, and fats for energy. Some good sources of Vitamin B5 is from meats, peas, and whole grain cereals

Vitamin B6:

Pyridoxine is another name for Vitamin B6. Vitamin B6 working along with B12 and B9 helps prevent heart attacks. Just like B2 B3 and B5 this vitamin helps the body process proteins, carbohydrates, and fats into energy. Some good sources of B6 is from meats, eggs, soybeans, whole grains, and nuts.

Vitamin B7:

Vitamin H or Biotin are other names for Vitamin B7. Vitamin B7 helps the formation of fatty acids and glucose to be used as fuel for the body. Some Good sources of B7 is from bananas, yeast, cereal, and liver.

Vitamin B9:

Folic Acid is another name for vitamin B9. It is very important during pregnancy since it is used for making and maintaining new cells. B9 prevents anemia by keeping up the production of red blood cells and prevent low birth weight and prematurity in births. Some good sources of B9 is from mushrooms, leafy greens, peas, and broccoli.

Vitamin B12:

Cobalamin is another name for vitamin B12. It works with B9 in keeping red blood cells healthy and also helps keep the central nervous system healthy. Some good sources of B12 are meat, eggs, and dairy. The two organizations that create guidelines for vitamin intake are by the Food and Nutrition Board of the National Academy of Sciences and the Food and Drug Administration(FDA).

Disruption in vitamin metabolism[edit]

Excess consumption of ethanol can lead to biochemical changes in the body, which further interrupts the vitamin A metabolism. Since both ethanol and retinol, the animal form of vitamin A, are alcohols, they are likely to interact and compete with each other for the same pathways; this also means they are likely to disrupt one another’s reaction. Retinol, like ethanol, reacts with dehydrogenases. The reaction forms retinoic acid. In the case of overconsumption of ethanol, retinol’s functions are affected. The retinoic acid signaling pathway is disrupted by the metabolized ethanol, which leads to various cancers and fetal alcohol syndrome.

People who often drinks may likely to develop Wernicke-Korsakoff syndrome, a disorder that affects the brain due to an insufficient intake of vitamin thiamine. Some characteristics of Wernicke-Korsakoff syndrome are confusion and abnormal movement of the limbs and eyes. Because thiamine can be converted to thiamine pyrophosphate, a coenzyme that is part of the pyruvate dehydrogenase complex, the insufficiency of thiamine leads to the formation of an altered pyruvate dehydrogenase complex that causes neurological defects.

Alcoholics often observed to have scurvy. Scurvy is a disease due to low level of vitamin C in the body. People with scurvy experience easy bruise, gum disease, loss of teeth, abnormal changes of the skin, and other symptoms. These symptoms appear because the lack of vitamin C stops the production of collagen, which is a protein fiber that makes up most of the dry skin weight. More specifically, vitamin C is needed for the production of the enzyme called prolyl hydroxylase. Prolyl hydroxylase is in charge of producing an amino acid, 4-hydroxyproline, that is needed in collagen. Hydroxyproline is essential because it forms hydrogen bond within the collagen triple helix, thus making the collagen more stable.


Dietary Supplement Information[edit]

The Institute of Medicine has created a few guidelines for people to reference on how much to take, recommended requirements, and what would be considered too much.
This is also known as the Dietary Reference Intake(DRI)(2):
The applications of RDA are: evaluating the adequacy of the national food supply, establishing a nutritional policy for public institutions and organizations, establishing labeling regulations, and setting guidelines for product formulation. The amount of vitamin intake for children, males, and females can be found on this external link: (1)

Recommended Dietary Allowance(RDA): is the average intake per day that satisfies the nutrient requirement for about 97-98% of all people whom are healthy in a gender group or life group.

Adequate Intake: is the recommended amount to intake, based on estimations of nutrient intake by people who are healthy and this amount is assumed to be sufficient. This measurement is used when the Recommended Dietary Allowance is unable to be determined.

Tolerable Upper Intake level: this is the utmost upper limit that is permitted without any detrimental risk to health and well-being for most of the people of a population. Ingesting or taking over this limit, increases the probability of detrimental effects significantly.

Estimated Average Requirements: daily intake number that has been evaluated to suffice 50% of the healthy peoples of a particular age or gender group.

Deficiency or Excess: although vitamins are essential building blocks of the human body, too much or too less of these compounds could be dangerous. An example would be the deficiency of folic acid (one of the vitamin B's) and a derivative of vitamin B2 called FAD. These two molecules help regulate the production of a potentially harmful compound called homocyesteine. Homocyestein is an essential intermediate of the production of an essential non-toxic amino acid methionine. To help lower the risks of this compound, vitamin B helps improving the fit of the enzyme that converts homocyestein to methionine. The deficiency of vitamin B in this case could increase the risk of heart attacks, strokes, and in the case of pregnant women, child defects. (7)

Vitamin Deficiencies and Excess(1)[1]

Vitamin Deficiency Excess
Vitamin A
mild - night blindness, diarrhea, impaired vision
severe - eye inflammation, causes blindness in children, keratinization of eyes and skin
||
Headache, vomiting, hair loss, irritability, liver and bone damage, blurred vision
Intracranial pressure, dizziness, nausea, headaches, liver damage.
Vitamin D
severe - children will get rickets, or softening and or weakening of bones; adults will get osteomalacia, which is also softening of the bones
brain, cardiovascular, and kidney damage
Vitamin E
Potential of anemia is babies that are born with a low-weight, deterioration of nervous system
Increase the risk of heart failure; can act as an anticoagulant and excessive intake may increase the risk of over bleeding.
Vitamin K
Results in extreme bleeding.
liver damage, anemia
Vitamin C
dry skin, anemia, and bruising.
Gastrointestinal sickness
Vitamin B
(it can be one of eight types of B vitamins): (3)
Cheilosis (Inflammation of the lips where there is scaling and fissures), photophobia (fear of bright light), Glossitis(inflammation of the tongue)
||
ranges from symptoms such as liver damage (B2) to poor coordination and numb feet (B6)

Amount of Vitamins Needed Per Day(4)

Amount for adult Males/Females

Vitamin A - 1000mcg/800mcg

Vitamin B1 - 1.5 mg/1.1 mg

Vitamin B2 - 1.7 mg/1.1 mg

Vitamin B3 - 15–19 mg/15 mg

Vitamin B5 - 4–7 mg/4–7 mg

Vitamin B6 - 2 mg/1.6 mg

Vitamin B7 - 30-100mcg

Vitamin B9 - 200mcg/180mcg/400mcg for pregnant women/280mcg for breast feeding

Vitamin B12 - 2mcg/2mcg

Vitamin C - 60 mg/60 mg

Vitamin D - 5mcg/5mcg for 19-51 year olds and 10mcg/10mcg for 51 and older

Vitamin E - 10 mg/8 mg

Vitamin K - 80mcg/65mcg

Introduction to Cofactors[edit]

Cofactors are small molecules or compounds that bind to enzymes and allow the enzymes to function. Cofactors are not proteins nor amino acids. Enzymes catalyze many type of reactions. However, most of the enzymes require the presence of cofactors in order to be active. The cofactor's role and mechanism varies with different enzymes. Usually, cofactors perform chemical reactions that the twenty amino acids cannot undergo. Proteins can perform acid-base reactions, form certain covalent bonds, and engage in intermolecular interactions. However, proteins are not equipped to facilitate reactions involving oxidation-reduction and group transfers.

Inactive enzymes without a cofactor attached are referred to as apoenzymes. Conversely, enzymes that are complete with cofactors and ready to catalyze reactions are called holoenzymes.

There are two categories of cofactors: metals and coenzymes. Metal cofactors are essentially metal ions, such as Zn2+, Mg2+, and Ni2+. Coenzymes are small organic compounds, commonly generated from vitamins. Furthermore, coenzymes are characterized by how strong they bind to their respective enzymes. Coenzymes that bind strongly to enzymes are called prosthetic groups. The enzyme-coenzyme complexes with prosthetic groups are generally permanent. In others words, the prosthetic group does not dissociate from the enzyme. Coenzymes that loosely bind to enzymes function like cosubstrates. In this case, the enzyme-coenzyme complexes can form and dissociate, which make the enzyme active or inactive. [2][3]

Some Coenzymes and their Respective Enzymes

Coenzyme Enzyme
Thiamine pyrophosphate Pyruvate dehydrogenase
Flavin adenine nucleotide Monoamine oxidase
Nicotinamide adenine dinucleotide Lactate dehydrogenase
Pyridoxal phosphate Glycogen phosphorylase
Coenzyme A (COA) Acetyl COA carboxylase
Biotin Pyruvate carboxylase
5'-Deoxyadenosyl cobalamin Methylmalonyl mutase
Tetrahydrofolate Thymidylate synthase

[4]

Coenzyme Functions:

Thiamine pyrophosphate: helps with tissue respiration.

Coenzyme A transports acetyl groups from one substrate to another subtrate.

For more information on Cofactors, see Cofactor (biochemistry).

References[edit]

1. Anderson, J. and L. Young. "Fat-Soluble Vitamins." Food and Nutrition Series. No.9.315. 2008 August. <http://www.ext.colostate.edu/pubs/foodnut/09315.html>.
2. "Dietary Reference Intakes: An Update." International Food Information Council Foundation. 2002 August. <http://www.ific.org/publications/other/driupdateom.cfm?renderforprint=1>.

  1. Campell, Neil (2007). Biology. Benjamin-Cummings Pub. 
  2. Berg, Jeremy; Lubert Stryer, John L. Tymoczko (2006). Biochemistry. W. H. Freeman Company. 
  3. Voet, Donald; Judith G. Voet, Charlotte W. Pratt (2008). Fundamentals of Biochemistry. New York: John Wiley & Sons. 
  4. Berg, Jeremy; Lubert Stryer, John L. Tymoczko (2006). Biochemistry. W. H. Freeman Company. 

3. Thiamin pyrophosphate. <http://www.uic.edu/classes/phar/phar332/Clinical_Cases/vitamin%20cases/thiamin/thiamin_pyrophosphate.htm Cofactor functions>

4. Vitamins. <http://www.lifeclinic.com/focus/nutrition/>

5. Campell. "Chapter 41 Animal Nutrition." Biology. 8th ed. Benjamin-Cummings Pub, 2007. 877. Print.

6. Holick, F. Michael, :Vitamin D." Boston University Medical Center, Boston. 1999

7. "The Chemistry of Health", NIH Publications, reprinted August 2006

8. Berg, Jeremy "Biochemistry", Chapter 27 The Integration of Metabolism. pp 812-813. Seventh edition. Freeman and Company, 2010.

9. Leo, MA ; Lieber, CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. AMERICAN JOURNAL OF CLINICAL NUTRITION Volume: 69 Issue: 6 Pages: 1071-1085 JUN 1999