Vitamins

vitamins5.jpg___

Vitamins are essential organic (carbon containing) compounds, needed in small amounts for normal functioning of the human body's metabolism, growth and reproduction.

A vitamin is called "essential" because either we can't make it in the body (called synthesis) or that we make too little of it for good health. For example, humans can't synthesize vitamin C (ascorbic acid) and therefore, we must obtain it through our diet. On the other hand, we can synthesize enough vitamin D in our skin if we can get sufficient exposure to sunlight. However, if we can't get enough sun, we may find ourselves deficient in vitamin D and therefore should obtain vitamin D as part of our diet.

The 13 or so vitamins that we use all play important roles in sustaining life. Fat-soluble vitamins that we need include vitamins A, D, E and K. Fat-soluble vitamins dissolve in fat and therefore can be stored in the fatty tissues of the body. As a consequence, we do not need to ingest fat-soluble vitamins daily. The body can use these stores when the intake of fat-soluble vitamins is low.

An assortment of B vitamins and vitamin C are the water-soluble vitamins that we require. Water-soluble vitamins dissolve in water and not in fat and therefore cannot be stored in the fatty tissues of the body. Because water-soluble vitamins mix easily with intracellular fluids, which are mostly water, they are fairly rapidly excreted via the skin (sweat) and the kidneys (urine). In order to avoid a deficiency, water-soluble vitamins are needed on nearly a daily basis.

Did you know that the word vitamin comes from the word "vitamine?" It's true! Vitamine, which means "vital amine," was coined in 1911 by the Polish-American biochemist Casimir Funk because it was thought at the time that these substances contained amines, compounds that have nitrogen (N) as part of their molecular structure. The letter "e" in vitamine was later dropped when it was determined that not all vitamins contained nitrogen. It was Casimir Funk who discovered vitamin B1 (thiamine).


Vitamin A (Retinol)

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Vitamin A has many Important Functions:



Vitamin A (also called retinol) is fat-soluble, and as such, can be stored in the fatty tissues of the body, although much the body's vitamin A is stored in the liver as retinyl palmitate. We obtain vitamin A either directly from foods that are substantial in vitamin A (beef liver, fish liver oils, egg yolks and butter, for example) or by converting a substance called beta-carotene into vitamin A.

Beta-carotene is the provitamin for vitamin A, that is, it can be converted to vitamin A. Provitamins are substances that are transformed into vitamins in the body. The amino acid tryptophan is another example of a provitamin. Tryptophan can be converted to vitamin B3 (niacin).

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Beta-carotene comes from a group of compounds called the "carotenoids." These are substances, which exhibit characteristic yellow and orange colors. Carrots, for example, are high in beta-carotene and other carotenoids. In addition to the role it can play as a provitamin for vitamin A, beta-carotene also functions as an important antioxidant compound, protecting cells from the harmful effects of free radicals.

Dark-green leafy vegetables (spinach and mustard greens) and yellow-orange fruits (papaya, apricots and mango) and vegetables (carrots, yams, yellow squash and sweet potatoes) are all good sources of beta-carotene. You need to eat approximately six times as much beta-carotene to get the same amount of vitamin A as in retinol.


Vitamin D

Did you know that sunlight is a natural source of vitamin D?

That's why Vitamin D is called the Sun Vitamin.


Vitamin D3 is synthesized in the body when ultraviolet light (mostly UV-B radiation) strikes our skin. Fair-skinned people need 20 to 30 minutes a day in bright sunlight to meet their vitamin D needs. The darker your skin the longer you will need to be in the sun in order to make enough vitamin D. Overcast skies, smog, clothing and sunscreens all decrease your exposure to UV-B radiation and hence decrease the amount vitamin D you can produce from sunlight. Although overexposure to sunlight can give you sunburn, it will not cause vitamin D toxicity. We can also meet our vitamin D needs with vitamin D fortified foods (milk, for example is one) and vitamin D supplements.


Vitamin D is important for a number of reasons:



Vitamin D is actually a family of fat-soluble sterol compounds:



For humans, the two most important forms of vitamin D are vitamin D2 and vitamin D3. Vitamin D2 (ergocalciferol) is derived from plants and irradiated yeast and fungi. Vitamin D3 is synthesized in the body when our skin is exposed to sunlight and we can obtain vitamin D3 from foods like milk, fortified cereals, tuna, salmon and fish oils.

Vitamin D2 and vitamin D3 have equal biological activity and therefore, both can be converted first to calcifediol in the liver and then to calcitriol, also known as 1,25-dihydroxycholecalciferol, in the kidneys. Calcitriol, which is the most active form of vitamin D3, is then transported via a carrier protein to the various sites in the body where it is needed.


__Converting Vitamin D3 to its active form:



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__Calcitriol (1,25-dihydroxycholecalciferol)



Vitamin E

When a biochemist or nutritionist talks about fat-soluble Vitamin E, they're really talking about a family of eight different vitamin E molecules. Four of the eight vitamin E molecules are called tocopherols (alpha, beta, gamma and delta) while the remaining four are called tocotrienols (alpha, beta, gamma and delta).

Vitamin E products labeled "Natural Tocopherol," for example, are a mixture of alpha-, beta-, gamma- and delta-tocopherol. In humans, d-alpha-tocopherol (also known as RRR-alpha-tocopherol) appears to be the most biologically active of the tocopherols because it is found in the highest quantities in the blood and tissues of the body. As a consequence, d-alpha-tocopherol is also the only form of vitamin E that meets the latest Recommended Dietary Allowance (RDA) for vitamin E.


Recommended Dietary Allowance (RDA) for d-alpha-tocopherol:

Children 1-3 years_________6 mg _(9 IU)
Children 4-8 years_________7 mg _(10.5 IU)
Children 9-13 years________11 mg (16.5 IU)
Adolescents 14-18 years____15 mg (22.5 IU)
Adults___________________15 mg (22.5 IU)


IU stands for "International Units" and its measure for a particular vitamin depends on the biological activity or "potency" of the substance from which the vitamin is obtained as agreed upon by international standards. International units for various vitamin E containing substances, both "natural" and "synthetic," have been determined:


Natural Vitamin E

1 IU = 0.735 mg d-alpha tocopheryl acetate
1 IU = 0.671 mg d-alpha tocopherol
1 IU = 0.861 mg d-alpha tocopheryl succinate

Synthetic Vitamin E

1 IU = 1 mg dl-alpha tocopheryl acetate
1 IU = 0.91 mg dl-alpha tocopherol



In foods, alpha-tocopherol is in the form of d-alpha-tocopherol, which is the vitamin E isomer preferred by the body. Vitamin E is present in animal fats, cereal grains and nuts. Alpha-tocopherol is found in a number of oils, including safflower and sunflower. It is also found in wheat germ. Soybean and corn oils contain mainly gamma-tocopherol.


d-Alpha-Tocopherol





Some of the Important Functions of Vitamin E

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Vitamin K


___The Anti-Hemorrhagic Vitamin


Vitamin K, yet another of the fat-soluble vitamins (A, D, E and K) was first isolated in 1939 by the Danish biochemist Henrik Carl Peter Dam. Dr. Dam, won the Nobel Prize in Medicine along with the American biochemist Edward Adelbert Doisy for their work, involving vitamin K. Ten years earlier, it was shown that this fat-soluble substance present in green leafy vegetables was required for normal coagulation of the blood.


The "K" in vitamin K comes from the German word "koagulation," which refers to blood clotting (coagulation). Vitamin K is essential for the functioning of several proteins involved in normal blood clotting. More specifically, vitamin K is needed for the body to make four of the blood's coagulation factors, including prothrombin (also known as factor II), proconvertin (factor VII), Christmas factor (factor IX) and the Stuart-Power factor (factor X).




When we receive a cut, we set into motion a complex series of events that act to stop the bleeding. Blood clotting is the body's response to tissue or endothelial injury.



The first step involves the constriction of the ruptured blood vessel thus slowing the flow of blood in an attempt to minimize blood loss.

Blood coagulation proteins soon arrive on the scene, starting a process known as the "coagulation cascade." Through the interaction of coagulation factors, platelets and the damaged vessel itself, a clot results. The clot forms a protective barrier over the injury. As the wound heals the clot slowly breaks down.


There are several forms of vitamin K, namely:



Vitamin K1 or "phylloquinone," which is the major dietary source of vitamin K, is found in green leafy vegetables like lettuce, kale, parsley, spinach and various greens (turnip, beet and mustard). Broccoli is also a good source of vitamin K1 as are certain vegetable oils (soybean, cottonseed, canola, and olive).


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Vitamin K2 is actually a group of compounds called the "menaquinones." Individual menaquinone compounds are generally designated either by the number of isoprene residues in the side chain of the vitamin K2 molecule or by the number of carbons in the side chain. For example, menaquinone-4 (MK-4) has four isoprene units in the side chain of vitamin K2, whereas menaquinone-7 (MK-7) has seven isoprene units in the side chain.


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Vitamin K2, which is the most biologically active form of vitamin K, is found in egg yolks, butter, liver, cheddar cheese and yogurt. If you can stand the strong smell and taste, a product called natto (fermented soybeans) is an especially good source of vitamin K2. Vitamin K2 is also produced by certain "friendly" intestinal bacteria in humans and it has been suggested that products like yogurt, kefir and acidophilus milk (fermented milk) may help to increase the functioning of these useful bacteria.



Vitamin K3 or "menadione" is a fat-soluble synthetic (man-made) vitamin K compound, used mainly in animal feed and pet foods. Although vitamin K3 is converted to vitamin K2 in the body, it is generally not recommended for use in humans.


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B-vitamins (B1, B2, B3, B5, B6, B7, B9 and B12)


The B vitamins are a group of eight water-soluble vitamins: Thiamin (B1), Riboflavin (B2), Niacin (B3), Pantothenic Acid (B5), Pyridoxine (B6), Biotin (B7), Folic Acid (B9) and Cobalamin (B12). B-Complex vitamin formulas, for example, contain all of the B-vitamins and several vitamin-like compounds: Choline, Inositol, and Para-aminobenzoic Acid (PABA).

B-vitamins are essential for a wide range of biological processes. B-vitamins act as coenzymes and unite with certain protein molecules to form active enzymes. These enzymes function as catalysts in important biochemical reactions, such as turning carbohydrates into energy and metabolizing proteins and fats. A catalyst speeds up or slows down a chemical reaction without the catalyst itself being consumed in the reaction.

Because the B-vitamins are water-soluble, they tend not to be stored in the body for long periods to time like the fat-soluble vitamins, which can be stored in the fatty tissues of the body. Consequently, it is important that we continually replenish B-vitamins by eating a well-balanced diet that is high in essential nutrients.



Let's peer into the World of the B-vitamins !__




Vitamin B1 (Thiamine)


____Thiamine

Vitamin B1, known as thiamine is also sometimes called aneurine. Thiamine, which was first isolated in the 1930's, was one of the first organic compounds to be recognized as a vitamin. In the human body, thiamine exists both as free thiamine and in several phosphorylated forms, including thiamine monophosphate, thiamine diphosphate (more commonly known as thiamine pyrophosphate) and thiamine triphosphate.


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Phosphorylation in this case, simply means adding phosphate (-PO43-) groups to thiamine. The phosphate groups come from a molecule called ATP or "adenosine triphosphate." Actually, to make thiamine pyrophosphate from thiamine (vitamin B1) requires not only ATP, it requires magnesium and an enzyme called thiamine pyrophosphokinase, as well.


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Did you know that ATP is regarded by many scientists to be the most important substance in biochemistry?


Thiamine pyrophosphate is a cofactor (also called a coenzyme) for several very important enzymes that help convert foods into energy. Cofactors may be organic or inorganic and may be loosely or tightly bound to the enzyme. A tightly bound cofactor (for example, heme in hemoglobin) is called a prosthetic group. Thiamine is essential, for example, for the metabolism of complex carbohydrates into the simple sugars (glucose).

Coenzymes are the functional part of enzymes, turning "inactive" enzymes (called apoenzymes) into "active" enzymes (called holoenzymes). When we say active, we mean catalytically active as enzymes are catalysts in biochemical reactions. Catalysts speed up or slow down chemical reactions, but are not consumed in the overall process. The protein part of an enzyme is called the apoenzyme. When a coenzyme chemically bonds to the inactive apoenzyme an active holoenzyme is formed. Many coenzymes are derived from vitamins, which is why vitamins are vitally important to our survival.

For enzyme-catalyzed reactions, a cofactor is something other than the enzyme itself that is required. Cofactor is a general term. A cofactor may be organic or inorganic (e.g., metal ions), and may be loosely or tightly (even covalently) bound to the enzyme. An organic cofactor is called a coenzyme; NADH and heme are common examples. NADH is loosely bound to the enzyme. Heme is covalently bound; a tightly bound cofactor such as this is called a prosthetic group. These terms have developed over time, and are not always used precisely. Note that heme is a coenzyme that is also a prosthetic group.

Thiamine is stored in small amounts (25 to 30 mg) in organs with high metabolic needs, such as the skeletal muscles, heart, brain, liver and kidneys. Because these stores are depleted quickly (2 to 3 weeks), thiamine should be a regular part of our diet.

Thiamine is also important for the proper functioning of nerve and muscle cells. As a coenzyme thiamine plays an important role in chemical reactions that stimulate the release of acetylcholine, an important neurotransmitter.


________Acetylcholine

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Neurotransmitters like acetylcholine are molecules that carry signals from one nerve cell to another, traveling across the space or gap between nerve cells. The gap between nerve cells (also known as neurons) is called a synapse.


___Nerve transmission at the synapse




Excellent Sources of Vitamin B1:

Great sources of vitamin B1 (thiamine) include meat, pork, beef liver, egg yolks and salmon, whole grain cereals and flours, wheat germ, brown rice, soy, navy, kidney and garbanzo (chickpeas) beans, sunflower seeds and peanuts and brewer's yeast (if you can stand the taste).




Vitamin B2 (Riboflavin)


______Riboflavin


Vitamin B2 (Riboflavin) is another important B-vitamin involved with the metabolism of carbohydrates, proteins and fats. Riboflavin was once known as vitamin G.


_______Riboflavin (Vitamin B2)


Riboflavin is composed of an isoalloxazine ring system linked to ribitol. Ribitol is a 5-carbon alcohol (C5H12O5) formed by the reduction of ribose, an important 5-carbon sugar (pentose).

isoallox1.jpg__________

____________________________________________________Ribitol


The isoalloxazine ring in vitamin B2 is both an electron donor and an electron acceptor and this is why vitamin B2 (riboflavin) is a component of the flavin coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These two important flavin molecules are required for enzyme catalyzed oxidation-reduction reactions connected with energy metabolism. [Flavin mononucleotide (FMN) is also called riboflavin phosphate.]


____________________

__Flavin Mononucleotide (FMN)________Flavin Adenine Dinucleotide (FAD)


For a biochemist, oxidation-reduction reactions are electrochemical reactions that are generally concerned with the addition of either oxygen or hydrogen to a biomolecule. In chemistry, oxidation is a term that is used to signify a loss of electrons from an atom or molecule, while reduction is a term used to describe a gain of electrons.

For example, if iron (II) is oxidized to iron (III), then the following oxidation reaction has taken place:

Fe+2_ _Fe+3 + e-

Oxidation has increased the oxidation state of iron (Fe) from +2 to +3.


The reverse reaction is a reduction reaction, whereby iron (III) gains an electron to form iron (II).

Fe+3 + e-_ _Fe+2

Reduction has decreased the oxidation state of iron (Fe) from +3 to +2.


There's a fun way for you to remember the difference between oxidation and reduction and it's called, "LEO the lion says GER."

LEO stands for Loss - of - Electrons - is - Oxidation

GER stands for Gain - of - Electrons - is - Reduction


Oxidation-reduction reactions come in pairs and are known collectively as "redox" reactions, for short. In other words, redox reactions match an oxidation reaction with a corresponding reduction reaction. If one species in the redox pair is being oxidized then the other species in the pair must be reduced and vice versa.


Flavin adenine dinucleotide (FAD) is an electron acceptor. FAD is the oxidized form of the coenzyme required for a number of enzyme catalyzed redox reactions connected with carbohydrate and fat metabolism. When FAD accepts two electrons (2 e-) as shown by the following reaction, it becomes FADH2, which is the reduced form of the molecule. FADH2 functions as an electron carrier in these reactions.


__+ _2H++_2e-
_____FAD___________________________________FADH2




Excellent Sources of Vitamin B2:

Milk is perhaps the best single source of vitamin B2 (riboflavin), containing nearly two milligrams of riboflavin per quart, which is enough riboflavin per day for both children and adults.

Other good sources of riboflavin include various cheeses, yogurt, eggs, liver, beef, chicken, pork, tuna, dark green vegetables such as broccoli and spinach, cereals, breads, wheat germ, wild rice, mushrooms, soybeans and brewer's yeast (again, if you can stand the taste). Eat up !!!



Vitamin B3 (Niacin)


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Vitamin B3 (also known as Niacin) is yet another of the B-vitamins needed for the conversion of foods into energy. Vitamin B3 was originally known as nicotinic acid before the name was changed to niacin, which is actually a term used to describe both nicotinic acid and nicotinamide.


Vitamin B3 (Niacin)


___nicotinicacid1.gif_________nicotinamide1.jpg_

__Nicotinic Acid__________Nicotinamide
Of the two forms of niacin it is nicotinamide that serves as a component in two important coenzymes required for energy metabolism: NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate). Because of the positive charge on the nitrogen (N) atom in the nicotinamide ring (as shown in the figures below) the oxidized forms of NAD and NADP are often depicted as NAD+ and NADP+, respectively.

NADP+ is synthesized from NAD+ by phosphorylating the ribose ring of NAD+ through the use of ATP. You can see from the two structures given below, how NADP+ is simply NAD+ with a third phosphate group (PO43-) attached to the ribose ring.


NAD+ (Nicotinamide Adenine Dinucleotide)


______NADox1.jpg____NAD+





NADP+ (Nicotinamide Adenine Dinucleotide Phosphate)


_______NADP+


Coenzymes NAD+ and NADP+ serve as electron acceptors (also called electron carriers) in important redox reactions in cells. By accepting H-, which is a gain of two electrons, NAD+ and NADP+ are converted to their respective reduced forms, NADH and NADPH. Both NADH and NADPH can transfer the two electrons to several types of electron carriers in the electron transport chain, which takes place inside the cell's mitochondria (within the inner membrane). In aerobic respiration, oxygen (O2) is the final acceptor of these electrons. Transfering the two electrons to the electron transport chain regenerates NAD+ and NADP+ so that they can again function as electron acceptors.



Making Niacin in the Body

Although our body can make niacin from tryptophan (one of the essential amino acids) the synthesis is rather slow. It is estimated that it takes 60 milligrams of tryptophan to make one milligram of niacin. Tryptophan is also needed to make serotonin, an important neurotransmitter. For these reasons it is prudent that we obtain niacin (vitamin B3) from additional dietary sources.

____Tryptophan


Fortunately, niacin can be found in quite a few foods. Good sources of niacin are protein-rich foods such as meats, chicken, fish, eggs, dairy products, various dried beans/peas and nuts. Soy products are also good sources of niacin. One-half cup of dry soybeans provides nearly 12 milligrams of niacin, while a 4-ounce slice of tofu contains nearly 16 milligrams of niacin. Fortified cereals are niacin-rich as well.


Vitamin B5 (Pantothenic Acid)


_____Pantothenic Acid


The name pantothenic acid is derived from the Greek word pantothen, meaning "from everywhere," and is so named because pantothenic acid is available in so many different foods.

Vitamin B5 (Pantothenic acid) is required for the synthesis of coenzyme A, which is required in a host of biochemical reactions that supply energy from foods (carbohydrates, fats and proteins).


___Coenzyme-A


Coenzyme-A is constructed from three different molecules: pantothenic acid, the amino acid cysteine and adenosine triphosphate (ATP).

As we saw in the section on Fat (Oils), the metabolism of fats requires acetyl-coA. From acetyl-coA a number of important molecules are synthesized, including triglycerides (fats), cholesterol, phospholipids, prostaglandins, and of course, ATP. Acetyl-coA is also required for the synthesis of acetylcholine, an important neurotransmitter and the hormone melatonin, which helps regulate sleep-wake cycles.

Pantothenic acid (vitamin B5) is also needed for the proper functioning of acyl-carrier protein (ACP), which participates in the synthesis of fatty acids.


Good sources of Vitamin B5 (pantothenic acid) are many: including all types of meats, chicken, fish, eggs, milk, cheese, dried beans and peas, various nuts, whole-grain breads and cereals, carrots, potatoes, corn, mushrooms, avocados, bananas, oranges and the list goes on and on.


Vitamin B6 (Pyridoxine)




Vitamin B6 is really a group of closely related molecules, including pyridoxine, pyridoxal, and pyridoxamine.

______________

____Pyridoxine____________Pyridoxal__________Pyridoxamine


All three molecules are efficiently converted mainly to pyridoxal phosphate, which is the biologically active form of vitamin B6 and to a lesser degree to pyridoxamine phosphate.


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___Pyridoxal phosphate


Conversion to pyridoxal phosphate requires the enzyme pyridoxal kinase. Pyridoxine hydrochloride is a more stable form of vitamin B6 and is the one found in commercial vitamins.

In plants, pyridoxine is the major form of vitamin B6. More specifically, pyridoxine in plants is bound to glucose as pyridoxine glucoside, which significantly lowers its bioavailability to us as a source of vitamin B6.

Pyridoxal and pyridoxamine, which are mainly found in animal tissues, have a much greater bioavailability.

Pyridoxal phosphate participates as a coenzyme (cofactor) in a wide variety of important biochemical reactions involving carbohydrate, protein and fat metabolism:


Breaking down amino acids requires the removal of the amino (NH3) group. This is done with the help of enzymes called transaminases (aminotranferases). With more than 20 amino acids needed by the human body it is no wonder that pyridoxal phosphate is a coenzyme (cofactor) for a large number of transaminases. Pyridoxal phosphate is also needed for the enzyme-catalyzed decarboxylation of amino acids. Decarboxylation means the removal of CO2. We examine transamination in the Proteins section.

Pyridoxal phosphate also serves as a cofactor for the enzyme glycogen phosphorylase, which is used in glycogenolysis (splitting of glycogen). We examine this in the Carbohydrates section.

Vitamin B6 is needed in the production of red blood cells (erythrocytes). Doctors, for example, prescribe vitamin B6 to treat certain types of anemia. Vitamin B6 also plays a vital role in maintaining the body's immune system.



Good sources of Vitamin B6:

A wide selection of foods are good sources of vitamin B6, including beef, pork, chicken, fish, eggs, liver, dairy products, brown rice, whole grain breads and cereals, soybeans and lentils, various nuts and seeds, potatoes, carrots, avocados, bananas and more.

The Recommended Daily Allowances (RDA) for vitamin B6 are shown below for children and adults. A medium-sized banana, for example, provides about 0.6 milligrams of vitamin B6.


Vitamin B6 (RDA)

Age:_____________milligram amount

Infants:________________0.3
6 to 12 months:_________0.6
1 to 3 years:____________0.9
4 to 6 years:____________1.3
7 to 10 years:___________1.8
11 to 18 years:__________2.2

Adults:

18 years and older_______2.2


It should be mentioned that vitamin B6 dosages exceeding 200 mg per day may lead to the reversible condition called peripheral neuritis. Symptoms include numbness of the extremities (hands and feet) and an inability to control muscles, for example, in walking.


Vitamin B7 (Biotin or Vitamin H)


_____________________________Vitamin B7 (Biotin)


Vitamin B7 or "Biotin" is sometimes called vitamin H and also coenzyme R. The name biotin derives from the Greek word bios, meaning "life." As a coenzyme, biotin plays important roles in a variety of biochemical processes including the metabolism of carbohydrates, protein and fats. People suffering from Type II diabetes may profit from biotin supplementation. Studies have revealed that biotin stimulates the release of insulin, lowering blood glucose levels and helping to keep them in check.

By the early 1930s, it was confirmed that biotin was an essential nutrient in mammals. Studies conducted during the 1920s (later to be referred to as egg white injury syndrome) in which large quantities of raw egg whites were included in the diets of rats produced symptoms including those of dermatitis, hair loss and impaired muscular coordination. It was determined that a protective factor in foods such as yeast and liver (later to be identified as biotin) helped protect the rats from egg white injury syndrome. The biochemical explanation for the syndrome, centers around a glycoprotein (glyco meaning "sugar containing") found in egg whites called avidin, which has a high affinity (attraction) for biotin. Formation of an indigestible avidin-biotin complex prevents the release of biotin to the tissues and biotin is subsequently lost through the feces, resulting in the eventual biotin deficiency of the recipient. It was also determined that by cooking raw egg whites the syndrome could be prevented. The heat from cooking alters or "denatures" the chemical structure of avidin thereby destroying its affinity for biotin and averting a biotin deficiency. It is therefore wise not to eat raw eggs (a practice adopted by some fitness enthusiasts). Eating raw eggs also exposes you to possible salmonella poisoning.



Biotin Molecule

The two figures below represent the biotin molecule. The figure on the right gives a more three-dimensional perspective in which the gray-colored spheres represent carbon C atoms, the blue spheres are nitrogen N atoms, the red spheres are oxygen O atoms, the yellow sphere is a sulfur S atom and the green spheres are hydrogen H atoms.

_biotin6.jpg _____


Biotin is relatively small, bicyclic (two-ring) compound formed from a tetrahydrothiophene (thiophene) ring and a second ring, which contains a ureido group. The thiophene ring also has a valeric acid side chain. Although eight different stereoisomers of biotin exist, only one stereoisomer is found naturally and to have biologically activity as a coenzyme. It is called d-(+)-biotin, D-biotin or simply biotin.


______Tetrahydrothiophene Ring


__cis-ureidogroup1.jpg__Ureido Group



_valericacid1.jpg__Valeric Acid


Valeric acid (also called pentanoic acid and propylacetic acid) is a short chain fatty acid that is attached to one of the carbons of the tetrahydrothiophene ring of biotin. Valeric acid is slightly soluble in water and soluble in alcohol and ether. Interestingly, it is used in a number of flavorings, perfumes, plasticizers and pharmaceuticals.


Biotin the Cofactor

Biotin is a cofactor in enzymes called carboxylases, which transfer carboxyl (CO2) groups in the form of bicarbonate (HCO3-) in a number of important biochemical processes, including the synthesis of glucose (known as gluconeogenesis) and fatty acids and the catabolism (breakdown) of certain amino acids. In humans, biotin participates in four different carboxylases:



Acetyl-CoA carboxylase (ACCase) catalyzes the binding of bicarbonate (HCO3-) to acetyl-CoA to form malonyl-CoA, which is the first step in the synthesis of fatty acids.


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It is malonyl-CoA, which serves as a substrate for the elongation of fatty acids. [A substrate is the substance on which the enzyme acts.] Fatty acid synthesis is discussed in the Fats section of this webpage. Check it out! ACCase is located both in the cell cytosol and mitochondria. The other carboxylases, propionyl-CoA carboxylase, pyruvate carboxylase and beta-Methylcrotonyl CoA carboxylase are found in mitochondria.


Propionyl-CoA carboxylase (PCCase) is needed for the catabolism of several amino acids, including methionine, threonine, leucine, isoleucine and valine. PCCase also helps break down odd-chain fatty acids and cholesterol. It is through PCCase that propionyl-CoA is converted to methylmalonyl-CoA via the addition of a carboxyl group from bicarbonate in the presence of ATP. Methylmalonyl-CoA can be transformed into succinyl-CoA an intermediate of the citric acid cycle (Kreb's cycle) and turned into energy in the form of ATP. [Vitamin B12 is also needed for this conversion.]


___Propionyl-CoA + CO2 _biotinarrow1.jpg _Methylmalonyl-CoA_b12arrow.jpg Succinyl-CoA


The following diagram shows more of the details of this conversion:


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Gluconeogenesis and the need for Pyruvate carboxylase (PCase):

The body (especially the brain) uses glucose for energy. During periods of extended fasting or starvation glycogen stores will be depleted. The body synthesizes glucose from noncarbohydrate sources (such as lactate, pyruvate, glycerol and most amino acids) in a process called gluconeogenesis, which simply means, "the creation of new glucose." Gluconeogenesis takes place mostly in the liver and to a lesser extent in the kidneys. Pyruvate carboxylase (PCase) is the pivotal enzyme in gluconeogenesis and catalyzes the transformation of pyruvate into oxaloacetate, an intermediate in the Kreb's cycle and the starting material for gluconeogenesis. Oxaloacetate is converted in a subsequent reaction to a compound called phosphoenolpyruvate or PEP. This is a guanidine triphosphate (GTP) dependent reaction that is catalyzed by the enzyme PEP carboxykinase. The two reactions and their respective enzymes are shown below.


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It was Prof. Merton F. Utter (1917-1980) who first demonstrated that the chemical reactions of gluconeogenesis were not the exact reversal of those found in glycolysis (breakdown of glucose). Utter and his coworkers discovered phosphoenolpyruvate carboxykinase and pyruvate carboxylase (PCase), two enzymes that work in concert to convert pyruvate to phosphoenolpyruvate (PEP) in a reaction sequence that differs from that of the glycolytic path.


Biotin is also a cofactor in the enzyme beta-methylcrotonyl-CoA carboxylase (beta-MCC), which is also known as 3-methylcrotonyl-CoA (3-MCC) and is required for the catabolism of the amino acid leucine a major constituent of muscle protein. Leucine is one of the nine essential amino acids in humans.

_____leucine1.jpg ______
_______Leucine

A 3-MCC deficiency occurs in some children blocking the normal metabolism of leucine and leading to the accumulation of unwanted metabolites. The condition is known as 3-Methylcrotonylglycinuria and is a type of leucine metabolism disorder or "organic acidemia." Organic acidemias (also called organic aciduria) are a group of inheritable genetic metabolic disorders in which a defect in protein metabolism occurs due to either the absence or malfunctioning of an essential enzyme. The defect results in the build up of non-amino organic acids, which are then excreted into the urine. The outcome is enhanced by the early diagnosis of the condition preferably within the first ten days of life. For more information concerning organic acidemia check out the Organic Acidemia Association website: http://www.oaanews.org/



How Biotin Works______________


Biotin present in foods is bound to specific proteins and must be released from these proteins before it can be absorbed through the small intestine. Attaching biotin to another molecule is referred to as "biotinylation." Action by proteolytic enzymes of the stomach and pancreas on protein-bound biotin results in a complex called biocytin (also known as epsilon-N-biotinyl-L-lysine) whereby biotin is attached to the amino acid lysine.


___________
_______Biocytin

Although biocytin is easily absorbed in the small intestine, the body can only use biotin in its free form, that is, without the lysine residue.

The enzyme biotinidase cleaves biocytin into biotin and lysine. Biotin is now free to perform its duty as a coenzyme by bonding to one of four different "apo-carboxylases" that use biotin. The biotin-apocarboxylase forms the complete enzyme, known in this instance as a "holo-carboxylase." [apo- means "away from or without" while holo-, which is also Greek, comes from the word holos meaning "whole."]

_______Biotin-Lysine Linkage


Biotin bonded to the apocarboxylase forms the "active" holocarboxylase


In humans, the four holocarboxylases are our old friends: acetyl-CoA carboxylase, propionyl-CoA carboxylase, pyruvate carboxylase and beta-methylcrotonyl-CoA carboxylase. Biotin is chemically bonded in each of these enzymes via an amide linkage between the carboxyl group of the valeric acid side-chain in biotin and the epsilon-amino group of the lysine residue in the apocarboxylase. The enzyme that catalyzes the formation of this covalent bond is called holocarboxylase synthetase.


The biotin-lysine linkage (shown above) forms a long crane-like "swinging arm," thus allowing the biotin ring to swing back and forth between two different active sites of the carboxylase enzyme.
We can demonstrate how these biotin-containing carboxylase enzymes work by using pyruvate carboxylase as an example. Pyruvate carboxylase is needed to catalyze the conversion of pyruvate into oxaloacetate. This is a multi-step process that can be summarized as follows:


In the initial step, ATP reacts with bicarbonate (HCO3-) to produce a molecule called carboxyphosphate.

______
____ ATP_ + _HCO3-_______

In the next step of the proposed mechanism, which is shown in the figure below, carboxylphosphate attacks the biotin portion of pyruvate carboxylase. In the attack, carboxylphosphate transfers its carboxyl group to a nitrogen N-1 atom contained in the ureido ring of biotin, thus forming carboxy-biotin.


At the other active site of pyruvate carboxylase the "activated" CO2 of carboxy-biotin is transferred to pyruvate converting pyruvate to oxaloacetate and releasing pyruvate carboxylase to perform another carboxylation. Each pyruvate carboxylase molecule can catalyze many such carboxylations before being converted back to biocytin.


Using Biotin to convert Pyruvate to Oxaloacetate




Good Sources of Biotin:

Although biotin can be found in a wide variety of foods, some sources are clearly better than other sources. Excellent sources of biotin include egg yolks, liver, milk, wheat germ and Brewer's yeast, which is generally found as a nutritional supplement. For those of you who would prefer other sources, biotin is found in fortified breads and cereals, rice, soybeans, peanuts, fish (herring and mackerel), mushrooms and bananas, just to name a few.

Royal jelly is also reported to be an excellent source of biotin. Royal jelly is a nutritious substance secreted by worker bees to feed bee larvae and eventual queen bees, hence the name "royal jelly." However, some people may have allergic reactions to royal jelly just as they may have such reactions to bee pollen. There are a multitude of health claims circulating concerning royal jelly, bee pollen and a substance known as propolis or "bee glue." Many of these health claims are simply too good to "bee" true.

As always, it is better to be an informed shopper. You might also like to check out the following website for information concerning health-related claims:
http://www.quackwatch.org/




Vitamin B9 (Folic Acid)


folicacid3B.jpg_____


Vitamin B9 or "folic acid" is also known as folate, folacin and vitamin M. Actually, it is folate that is found in a variety of leafy green vegetables and folic acid is a synthetic form of folate that is added to foods and vitamin/mineral supplements. Not surprisingly, the name "folate" is derived from the Latin word "folium" for leaf.

Folic acid has received much attention in recent times as one of the B-complex vitamins important for preventing neural tube defects (NTDs) in the developing human fetus. Research shows that women with folic acid deficiences are at higher risk of having a child with a neural tube defect. The good news is that research has also shown that this risk can be significantly reduced by 50 to 70% when women consume adequate amounts of folic acid prior to and during the first four to six weeks after conception. The U.S. Public Health Service recommends that women of childbearing age consume 400 micrograms (mcg) of folic acid daily.

Tragically, some women still bear children suffering from NTDs despite having taken folic acid supplements before and during pregnancy. Neural tube defects are referred to as a complex congenital disorder, which means that they are caused by changes in more than one gene. To further complicate matters are the various environmental factors (chemicals, medications and diet) that may predispose certain women to having children with NTDs. The data does not point to folic acid is a cure, but instead as a preventative measure in the fight against NTDs.

The neural tube is the embryonic structure that gives rise to both the brain and spinal cord. When the neural tube fails to close properly, a neural tube defect has occurred. The congenital abnormalities, spina bifida and anencephaly, are the two most common types of NTDs. Spina bifida occurs when the lower portion of the neural tube fails to close properly. Fortunately, the survival rate for babies born with spina bifida is high, on the order of 80 to 90%. Despite facing varying degrees of disability, many spina bifida children go on to lead productive lives. According to the Spina Bifida Association of America (SBAA) more than 70,000 people in the United States are living with spina bifida.

For more important information concerning spina bifida check out the SBAA website at
http://www.sbaa.org/site/PageServer?pagename=index




The Chemical Structure of Folic Acid


As shown in the figure below, folic acid (folate) is constructed from three molecules:



Folic Acid (Folate)

__
_______6-Methylpterin_____Para-aminobenzoic__Glutamic acid (glutamate)
_______________________________acid


The compound 6-Methylpterin is a bicyclic, heterocyclic pteridine ring system. All this means is that two different ring compounds, one called pyrazine and the other pyrimidine, have come together to form the two-ring pteridine molecule. This is illustrated in the figure below. The methyl (CH3) group in 6-methylpterin is attached to the number 6 carbon shown in red in the figure above.


_________+ ________pyrimidine1.jpg_______=_______pteridine1.jpg ___ _____

_Pyrazine_______________Pyrimidine_____________Pteridine



In addition to being a structural component of folic acid, the pteridine molecule is also part of the isoalloxazine ring system in vitamin B2 (riboflavin). Interestingly, pteridine is the parent compound of pterins like xanthopterin, a yellow pigment found in the wings of certain butterflies.

_______Xanthopterin



Para-aminobenzoic acid (PABA) takes its place in the middle portion of the folate molecule. PABA is not only readily available from various foods it is made by intestinal bacteria. PABA was one of the first chemical sunscreen agents. Although PABA is no longer employed as a sunscreen because it stained people's clothes, PABA esters are used in many sunscreens. PABA esters include glycerol PABA, padimate A and padimate O.


______Para-aminobenzoic acid (PABA)


Glutamic acid or glutamate is one of the non-essential amino acids that humans use in the construction of various proteins and protein-based molecules. It is non-essential in the sense that it can made when needed from simpler compounds in the body. The sodium salt of glutamic acid, known as monosodium glutamate or MSG is a popular flavor enhancer used in different food preparations.


_____Glutamic Acid

The black spheres represent carbon atoms, red is oxygen, blue is nitrogen and the white spheres are hydrogen atoms.



Tetrahydrofolate (THF): A Vital Coenzyme

Inside cells, folate is converted to its biologically active forms 7,8-dihydrofolate (DHF) and 5,6,7,8-tetrahydrofolate (THF). The conversion of folate to DHF, for example, is a reduction reaction whereby two hydrogen atoms are added to folate at the 7 and 8 positions of the pteridine moiety in folate. [Moiety means part or portion of.] This reaction is catalyzed by the NADPH-specific enzyme dihydrofolate reductase. The conversion of folate to THF requires two such reductions catalyzed by dihydrofolate reductase. Overall, four hydrogen atoms are added to folate (at positions 5,6,7 and 8 of the pteridine moiety) in converting it to 5,6,7,8-tetrahydrofolate.


____


Tetrahydrofolate (THF) is a vital coenzyme in reactions that involve the transfer of single carbon functional groups such as methyl (-CH3), methylene (-CH2) and formyl (-HC=O). THF serves both as an acceptor and a donor of these one-carbon atom units. For example, in the conversion of the amino acid serine to that of glycine it is tetrahydrofolate (THF) that accepts a methylene (-CH2) group from serine, thus transforming THF to 5,10-methylene-tetrahydrofolate. This conversion is illustrated in the figure below, for the acidic form of THF, known as tetrahydrofolic acid.



____


If you look closely at 5,10-methylene-tetrahydrofolic acid in the figure above, you will see that the methylene (-CH2) group is held between nitrogen atoms at positions 5 and 10 of 5,10-methylene-tetrahydrofolic acid. This is why the molecule is also known as N5,N10-methylene-tetrahydrofolic acid.

The usefulness of THF does not stop here. For example, the methylene (-CH2) group from 5,10-methylene-THF can be donated to deoxyuridine monophosphate (dUMP) converting it to deoxythymidine monophosphate (dTMP), the rate-limiting nucleotide in DNA synthesis. The conversion of dUMP to dTMP is shown in the following figure. The figure also illustrates how THF is first generated from DHF and is then converted to 5,10-methylene-THF, which is then converted back to DHF, starting the THF cycle over again. The three enzymes, thymidylate synthase, dihydrofolate reductase and serine transhydroxymethylase are also given for the various reactions taking place in this cycle.



______Deoxyuridine______________revarrows1A.jpg ________Deoxythymidine
____Monophosphate (dUMP)_______________Monophosphate (dTMP)


_______



Good Sources Folate (Folic Acid):

Folate is found in a variety of leafy green vegetables (spinach, broccoli and romaine lettuce), bell peppers, oranges, liver, egg yolks, rice, barley and various legumes (beans, peas and lentils). Folic acid is the synthetic form of folate and is added to a number of processed foods, cereals and breads. Folic acid is of course, found in vitamin/mineral supplements.



Vitamin B9 (Folic Acid): Recommended Daily Allowances (RDA)

Age: ____________________Amount (micrograms)

Infants up to 6 months:_____________30
6 to 12 months:____________________45
1 to 3 years:______________________100
4 to 6 years:______________________200
7 to 10 years:_____________________300
11 to 18 years:____________________400

Adults:

18 years and older:________________400



Folic Acid Alert:

People need to be aware of the relationship between vitamin B12 (cobalamin) and vitamin B9 (folic acid). Vitamin B12 and vitamin B9 deficiencies are both a common cause of anemia. Treating anemia solely with folic acid supplements and at dosages exceeding 1 milligram (1000 micrograms) per day can mask the symptoms of a vitamin B12 deficiency. The vitamin B12 contained in the foods that we eat is bound to proteins and must be subjected to hydrochloric acid in the stomach in order to release the vitamin B12. As we age, our ability to make stomach acid diminishes. As a consequence, seniors should be especially concerned of the interplay between vitamin B12 and vitamin B9 because they are at greater risk of having a vitamin B12 deficiency.


Vitamin B12 (Cobalamin)


_____The "Red" Vitamin

Vitamin B12, also called cobalamin, cyanocobalamin and hydroxycobalamin was the last of the "true" B-vitamins to be discovered. Although it was known by the 1920's, that an unknown compound in raw liver was responsible for curing some people of the life-threatening condition pernicious anemia, it wasn't until 1948 when Dr. E. Lester Smith and his research group isolated vitamin B12 from liver.

The Nobel Prize in Chemistry (1964) was awarded to Dorothy Crowfoot Hodgkin (a pioneer in the field of X-ray crystallography) for her determinations by X-ray techniques the structures of important biochemical compounds including that of vitamin B12. She elucidated the structure of vitamin B12 in 1955.

_____Dorothy Crowfoot Hodgkin (1910-1994)




______Vitamin B12 _ 


 The figure above shows the molecular structure of vitamin B12. Although it looks quite complicated, vitamin B12 is really built from some basic parts: a nucleotide and a corrin ring. The nucleotide is attached to the corrin ring as are a number of methyl groups and amino acid-like groups. The nucleotide consists of a nucleic acid (base), ribose sugar and phosphate (-PO4) group. The corrin ring (shown in blue in the figure) is constructed from four pyrrole groups. A cobalt (Co) atom (shown in red) resides at the center of the corrin ring. Attached to the cobalt atom is an R-group, which is shown in purple. The letter R is used to represent the respective groups associated with the two basic cobalamins and the two coenzyme forms of vitamin B12. For example, when R is cyanide (CN), then vitamin B12 takes the form of cyanocobalamin. In hydroxycobalamin, R equals the hydroxyl group (-OH). In the coenzyme forms of vitamin B12, R equals an adenosyl group in adenosylcobalamin and R equals a methyl (-CH3) group in methylcobalamin.


___


The corrin ring structure resembles that of the porphyrin ring found in hemoglobin and the chlorin ring found in chlorophyll. In hemoglobin, an iron (Fe) atom sits at the center of the porphyrin ring, whereas in chlorophyll, a magnesium (Mg) atom is at the center of the chlorin ring. The use of cobalt in vitamin B12 is the only known function of this metal in biological systems.


____

Knowing the molecular structure of vitamin B12 has helped scientists understand how the body uses the vitamin and gives insight into why vitamin B12 does not help everyone afflicted with pernicious anemia (a severe form of the blood disorder anemia). It was later determined that a glycoprotein compound that has come to be known as the "intrinsic factor" is required for the proper absorption of vitamin B12.

The vitamin B12 contained in the foods that we eat is bound to proteins and must be released from these proteins before we can utilize it. Hydrochloric acid, which is secreted by parietal cells lining the stomach, does the job of releasing vitamin B12. The now free vitamin B12 is quickly bound to glycoproteins called R-binders (haptocorrins) forming a vitamin B12/R-binder complex thus protecting it from being destroyed by the very hydrochloric acid that freed it.

The intrinsic factor, which is a sugar-containing protein, is secreted by the same parietal cells that secrete hydrochloric acid. The intrinsic factor binds to vitamin B12 (the "extrinsic factor") thus enabling its absorption through the small intestine and on into the bloodstream. In the stomach, the pH is low (acidic) and the affinity of vitamin B12 for the intrinsic factor is low while its affinity for the R-binders is high. This is good because it keeps vitamin B12 from being destroyed by the acid. Before vitamin B12 can bind to the intrinsic factor, the vitamin B12/R-binder complex must enter the small intestine (duodenum) where the pH is much closer to neutral than the acidic environment of the stomach. In the duodenum, the R-binders are cleaved from the vitamin B12/R-binder complex by proteases secreted by the pancreas. Vitamin B12 has now been safely released and can bind with the intrinsic factor and proceed to the lower portion of the small intestine. It then binds to a vitamin B12-specific binding protein and it transported via the bloodstream as transcobalamin.

The failure to produce the intrinsic factor results in pernicious anemia. The impaired production or improper utilization of the intrinsic factor can also result in pernicious anemia. The parietal cells are the same cells that secrete hydrochloric acid into the stomach. Hydrochloric acid helps the absorption of vitamin B12. As we age, hydrochloric acid production diminishes and if it becomes sufficiently weak, the absorption of vitamin B12 may become impaired.



How We Obtain Vitamin B12

Known as the "red" vitamin because it exists as a dark red crystalline compound, B12 is found in organ and muscle meats, fish, shellfish, dairy products, eggs and in fortified foods like breakfast cereals. Vitamin B12 is unique in that it is the only vitamin to contain cobalt (Co3+) metal ion, which by the way, gives it the red color. Strict vegetarians (those who avoid dairy products and eggs) are generally at risk of developing a vitamin B12 deficiency if they are not taking a vitamin B12 supplement. Tempeh and other fermented soybean products like tamari (soy sauce) and miso (soybean paste) may contain some vitamin B12, but they are not considered to be good sources of the vitamin. Sauerkraut and seaweed are also poor sources of vitamin B12.

Vitamin B12 in animal proteins is found for the most part in one of two coenzyme forms, adenosylcobalamin and methylcobalamin. The action of stomach acid and the enzyme pepsin dissociates these coenzymes from the animal proteins we ingest. Again, we can see why it is important to maintain a normal production of stomach acid.

The coenzyme forms of vitamin B12 serve a number of important functions. Adenosylcobalamin, for example, is the cofactor (coenzyme) for the enzyme methylmalonyl-CoA mutase, which in mitochondria converts methylmalonyl-CoA to succinyl-CoA. This conversion or "intramolecular rearrangement" is a process called isomerization. The reaction is associated with the breakdown (catabolism) of fatty acids having an odd number of carbons. The succinyl-CoA can be metabolized to produce energy via the Kreb's cycle or used in the synthesis of fatty acids.



____________revarrows1A.jpg________


People with elevated methylmalonic acid levels in their blood or urine are not sufficiently converting methylmalonyl-CoA to succinyl-CoA, which suggests that they may have a vitamin B12 deficiency.

Methylcobalamin is a cofactor for the enzyme methionine synthase, which catalyzes the conversion of the amino acids homocysteine to methionine via the transfer of a methyl group (-CH3). Actually, methylcobalamin has a partner in this reaction, that of 5-methyltetrahydrofolate, which is a derivative of vitamin B9 (folic acid). In this partnership, the methyl group from methylcobalamin is transferred to homocysteine, yielding methionine and cobalamin. After which, 5-methyltetrahydrofolate transfers its methyl group to cobalamin thus converting it back to methylcobalamin. This is illustrated in the following figure:


___


In losing a methyl (-CH3) group, 5-methyl-tetrahydrofolate becomes tetrahydrofolate or THF as it is called. We examined THF in the section concerning vitamin B9 (Folic acid) of this webpage. Check it out! THF is converted to 5,10-methylene-tetrahydrofolate, which is later converted to 5-methyl-tetrahydrofolate (also called N5-methyl-THF) so that the process of converting homocysteine to methionine can be continued.

The figures below compare THF and 5-methyl-tetrahydrofolate, which is called N5-methyl-THF because the methyl group (shown in red) is attached to nitrogen atom number 5 (shown in blue) of the ring system.


___Comparing THF and N5-methyl-THF


How Vitamin B12 Compounds Are Formed

During the early 1950s, scientists discovered that sludge obtained from the fermentation tanks of sewage plants had high concentrations of vitamin B12 compounds. By the late 1950s, Dr. Thressa Stadtman of the National Institutes of Health (NIH) demonstrated in her lab that vitamin B12 compounds were in fact, synthesized by methane-producing anaerobic bacteria. Anaerobic means "without oxygen" as opposed to aerobic, which indicates the presence of oxygen. Dr. Stadtman and her colleagues also uncovered five of the twelve known vitamin B12-dependent enzymes found in humans.


_______Dr. Stadtman in her lab (circa 1953).

Vitamin B12 is made by microorganisms like bacteria, fungi and algae and not by animals. However, the digestive systems of many animals can support vitamin B12 producing bacteria and therefore allow for the fermentation process to take place. Ruminant animals, for example, such as cattle and sheep have this ability and the vitamin B12 produced is then absorbed into their tissues (especially the liver). Humans can obtain vitamin B12 compounds from meat and dairy products.

The human body generally stores from 2 to 10 milligrams of B12 distributed mostly amongst the liver, kidneys and the nervous system. The liver, for example, can store enough B12 to last for several years. As a consequence, vitamin B12 is not needed daily as are most of the water soluble B-vitamins.


Recommended Daily Allowances (RDA) for :

Age: _______________________Amount in micrograms

Infants up to 6 months:________________0.5
6 to 12 months:______________________1.5
1 to 3 years:_________________________2.0
4 to 6 years:_________________________2.5
7 to 18 years:________________________3.0

Adults:
18 years and older:___________________3.0


One cup of milk or one large egg contains about 1 microgram of vitamin B12. One ounce of cheese of various types contains around 0.3 micrograms.