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Vitamins Essential to Human Nutrition

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The Science Behind Health With Doctor Bones (Don R. Mueller, Ph.D.) The Funny Man of Health Educator Entertainer J U G G L E R FOOD Scientist
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Page 1: Vitamins Essential to Human Nutrition

The Science Behind HealthWith Doctor Bones (Don R. Mueller,

Ph.D.)The Funny Man of HealthEducator

Entertainer

JU

G G LE

R

FOOD

Scientist

Page 2: Vitamins Essential to Human Nutrition

Vitamins are essential organic 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 cannot make it in the body (called synthesis) or that we produce too little of it for good health.

For example, humans cannot synthesize vitamin C. Therefore, we must obtain it via our diet. On the other hand, we can synthesize enough vitamin D in our skin if we receive sufficient exposure to sunlight. If we are sun deficient, then we may also find ourselves vitamin D deficient and must obtain vitamin D through our diet.

Page 3: Vitamins Essential to Human Nutrition

Vitamins

Fat-soluble A, D, E and K

Water-soluble

B1, B2, B3, B5, B6, B7, B9, B12, and

C

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

The 13 or so vitamins that we require for good health include the fat-soluble vitamins A, D, E and K and the water-soluble B-Vitamins (B1, B2, B3, B5, B6, B7, B9, B12) and Vitamin C.

Page 4: Vitamins Essential to Human Nutrition

The 13 or so vitamins that we require all play important roles in sustaining life. The 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.

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. In order to avoid a deficiency, water-soluble vitamins are needed on nearly a daily basis.

Page 5: Vitamins Essential to Human Nutrition

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).

DID YOU KNOW

Page 6: Vitamins Essential to Human Nutrition

A Science-Based Examination of the Fat-soluble Vitamins ( A, D, E and

K)

Page 7: Vitamins Essential to Human Nutrition

Fat-soluble Vitamins ( A, D, E and K)

Vitamin A (also called retinol) is fat-soluble, and as such, can be found in the body’s fatty tissues, although the majority is stored in the liver as retinyl palmitate. Vitamin A can be obtained either directly from foods that are substantial in vitamin A (e.g., beef liver, fish liver oils, egg yolks and butter) or by converting a substance called beta-carotene into vitamin A.

In 1913, the biochemist Elmer V. McCollum and his colleagues conducted nutritional studies that led to the discovery of vitamin A in butterfat and cod liver oil. McCollum originally called it "fat-soluble factor A" and then later "vitamine A."

Page 8: Vitamins Essential to Human Nutrition

An early sign of vitamin A deficiency is night blindness. You've probably heard the saying, “Carrots for good eyesight!" In truth, carrots contain a substance called "beta-carotene" (carotene, coming from carrots) which the body can convert to vitamin A when needed.

"Eat your carrots!”

Beta-carotene originates from compounds called "carotenoids." These substances exhibit characteristic yellow and orange colors. In addition to its role as a provitamin for vitamin A, beta-carotene also functions as an important antioxidant compound, protecting cells from the harmful effects of free radicals.

Page 9: Vitamins Essential to Human Nutrition

Vitamin A has many Important Functions:

Plays an important role in vision, especially night vision.

Helps regulate cell development.

Promotes the proper growth of bones and teeth.

Boosts the body's immune system helping to increase our resistance to infectious diseases.

Vital in the formation and maintenance of healthy hair, skin and mucous membranes.

Vitamin A holds an important place in sexual reproduction.

Page 10: Vitamins Essential to Human Nutrition

Vitamin D - "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 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. Fortunately, we can also meet our vitamin D needs with vitamin D fortified foods (milk, for example is one such item) and vitamin D supplements.

Page 11: Vitamins Essential to Human Nutrition

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 (cholecalciferol) as discussed previously, is synthesized in the body when we are exposed to sunlight and can be obtained from foods such as milk, fortified cereals, tuna, salmon and fish oils.

Vitamin D2 and vitamin D3 have equal biological activity. Both can be converted, first to calcifediol (a transport form of vitamin D) in the liver and then to the bioactive form of vitamin D, calcitriol (1,25-dihydroxycholecalciferol) in the kidneys. Calcitriol is then transported via a carrier protein to the various sites in the body where it is needed.

Page 12: Vitamins Essential to Human Nutrition

Some of the many useful functions of Vitamin D Vitamin D aids in the absorption of calcium and phosphorus from the small intestine for the normal mineralization of bone.

Vitamin D helps regulate calcium levels in the blood, ensuring that nerves and muscles function properly, as calcium is vital for nerve cell transmissions and muscle fiber contractions.

There is evidence that vitamin D (specifically, vitamin D3) is involved in regulation of the body's immune system.

Vitamin D is essential for normal insulin secretion by the pancreas and therefore control of blood sugar levels.

The bioactive form of vitamin D3, (calcitriol) is believed to play an important role in the regulation of the genes involved in cell growth, differentiation and proliferation.

Page 13: Vitamins Essential to Human Nutrition

Vitamin E - The Antioxidant VitaminThe fat-soluble Vitamin E, is actually a family of eight different vitamin E molecules. Four of the eight vitamin E molecules are called the tocopherols (alpha, beta, gamma and delta).

Foods containing significant amounts of tocopherols include a number of oils (corn, safflower, soybean, cottonseed and canola), nuts (almonds, hazelnuts, and walnuts), wheat germ and vegetables like spinach, kale, sweet potatoes and yams.

Page 14: Vitamins Essential to Human Nutrition

The remaining four Vitamin E molecules are known as tocotrienols (alpha, beta, gamma and delta). Sources of tocotrienols include: oils from palm, rice bran and annatto beans.

In foods, alpha-tocopherol is in the form of d-alpha-tocopherol (the vitamin E isomer preferred by the body), which is found in a number of oils, including safflower and sunflower. It is also found in wheat germ. “Trienol” refers to three C=C double bonds.

C=C double bonds

Page 15: Vitamins Essential to Human Nutrition

Some of the Important Functions of Vitamin E

Vitamin E in the form of d-alpha-tocopherol is an important fat-soluble antioxidant, scavenging oxygen free radicals: lipid peroxy radicals and singlet oxygen molecules before these various radicals can do further harm to cells.

Vitamin E helps maintain the structural integrity of cell membranes throughout the body.

The isomer, d-alpha-tocopherol has been shown to inhibit the aggregation or "clumping" of blood platelets, hence, helping to reduce the risk of heart attack and stroke.

Studies show that d-alpha-tocopherol protects the fat component in low-density lipoproteins (LDLs) from oxidation and exhibits moderate cholesterol-lowering capabilities.

Page 16: Vitamins Essential to Human Nutrition

Vitamin K - The Anti-Hemorrhagic Vitamin

Vitamin K, was first isolated in 1939 by the Danish biochemist Henrik Carl Peter Dam, later winning the Nobel Prize in Medicine in 1943, for his work involving vitamin K.

A decade earlier, it was shown that this fat-soluble substance (present in green leafy vegetables) was required for normal coagulation of the blood.

The "K" comes from the German word "koagulation.” Vitamin K is essential for the functioning of several proteins involved in normal blood clotting. Vitamin K is needed to make four blood coagulation factors, including: prothrombin (factor II), proconvertin (factor VII), Christmas factor (factor IX) and the Stuart-Power factor (factor X).

Page 17: Vitamins Essential to Human Nutrition

Vitamin K1 is the major dietary source of vitamin K and 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).

Vitamin K1 (phylloquinone)

There are three basic forms of vitamin K, namely:

Page 18: Vitamins Essential to Human Nutrition

Vitamin K2, which is the most biologically active form of vitamin K, is found in egg yolks, butter, liver, cheddar cheese and yogurt. Vitamin K2 is also produced by certain "friendly" intestinal bacteria in humans and it has been suggested that products yogurt, kefir and acidophilus milk (fermented milk) may help to increase the functioning of these useful bacteria.

Vitamin K2 (menaquinone)

Page 19: Vitamins Essential to Human Nutrition

Important Functions for Vitamin K

The primary role for Vitamin K in human health is in the regulation of normal blood clotting.

Vitamin K has been shown to improve bone health, particularly for those at risk for osteoporosis.

Used to reduce the hazard of bleeding in liver disease.

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. Vitamin K3

Page 20: Vitamins Essential to Human Nutrition

A Science-Based Survey of the B-Vitamins Thiamin (B1) Riboflavin (B2) Niacin (B3)

Pantothenic Acid (B5) Biotin (B7)

Pyridoxine (B6)

Folic Acid (B9) Cobalamin (B12)

B7

B9

Page 21: Vitamins Essential to Human Nutrition

In a wide range of biological processes, B-vitamins function as coenzymes, uniting with certain protein molecules to form active enzymes. These enzymes are catalysts in important biochemical reactions, such as turning carbohydrates into energy and metabolizing proteins and fats. A catalyst changes the rate of a chemical reaction without the catalyst itself being consumed.

The B-vitamins being water-soluble, tend not to be stored in the body for long periods to time. Consequently, it is important that we continually replenish B-vitamins via a well-balanced diet.

B-Complex vitamin formulas usually contain all of the B-vitamins and several vitamin-like compounds: namely, Choline, Inositol, and Para-aminobenzoic Acid (PABA).

LET US BEGIN OUR TOUR OF THE B-VITAMINS

Page 22: Vitamins Essential to Human Nutrition

The B vitamins are a group of water-soluble vitamins:

Thiamin (B1) Riboflavin (B2) Niacin (B3)

Pantothenic Acid (B5) Pyridoxine (B6)

Biotin (B7) Folic Acid (B9) Cobalamin (B12)

1 2 3

4 5

6 7 8

Eight

Page 23: Vitamins Essential to Human Nutrition

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.

Vitamin B1 (Thiamine or Thiamin)

In humans, thiamine exists both as free thiamine and in several phosphorylated forms:

(1) Thiamine monophosphate

(2) Thiamine diphosphate

(3) Thiamine triphosphate. Thiamine

1

Page 24: Vitamins Essential to Human Nutrition

Thiamine diphosphate (thiamine pyrophosphate) is the bioactive form of thiamin and a cofactor for several very important enzymes, which help convert foods into energy. Thiamine pyrophosphate (TPP) comprises both pyrimidine and thiazole ring structures along with a double-phosphate (pyrophosphate) group.

Thiazole ring

Pyrimidine ring

Pyrophosphate

The phosphates (PO43-) in

TPP, are taken from ATP. Actually, to make TPP from thiamine requires not only ATP, but also magnesium and the enzyme, thiamine pyrophosphokinase.

Thiamine Pyrophosphate (TPP)

Thiamine + ATP AMP + TPP

Page 25: Vitamins Essential to Human Nutrition

Thiamine in the form of TPP is essential for the metabolism of complex carbohydrates into simple sugars (glucose).

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

Great sources of vitamin B1 include 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, peanuts and brewer's yeast.

Page 26: Vitamins Essential to Human Nutrition

2 Vitamin B2 (Riboflavin) was once called Vitamin G.

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

Riboflavin

IsoalloxazineRing

Ribitol

Page 27: Vitamins Essential to Human Nutrition

Vitamin B2 (Riboflavin) is involved with the metabolism of carbohydrates, proteins and fats.

The isoalloxazine ring in vitamin B2 (riboflavin) is a component of the flavin coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).

FMN

FAD

Page 28: Vitamins Essential to Human Nutrition

Both FMN and FAD are required for enzyme catalyzed oxidation-reduction (redox) reactions connected with energy metabolism. The tricyclic isoalloxazine ring system (in FMN and FAD) is the center of attention in these redox reactions.

For example, flavin adenine dinucleotide (FAD) is the oxidized form of the coenzyme required for several redox reactions connected with carbohydrate and fat metabolism. When FAD accepts two electrons (2 e-), it becomes FADH2 (the reduced form

of FAD). The FADH2 is an electron carrier in these reactions.

FAD FADH2

+ +2 H+ 2 e-

Page 29: Vitamins Essential to Human Nutrition

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.

Excellent Sources of Vitamin B2:

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.

For the biochemist, Oxidation-Reduction reactions are electrochemical processes that are generally concerned with the addition of either oxygen or hydrogen to a biomolecule. In chemistry, the term “Oxidation” signifies a loss of electrons from an atom or molecule, whereas “Reduction” suggests a gain of electrons.

Page 30: Vitamins Essential to Human Nutrition

Vitamin B3 (Niacin)3

Vitamin B3 (Niacin) is yet another of the B-vitamins needed for the

conversion of foods into energy. Vitamin B3 was originally called nicotinic acid before being changed to niacin, which is actually a name used to describe both nicotinic acid and nicotinamide.

Nicotinic acid Nicotinamide

Page 31: Vitamins Essential to Human Nutrition

It is the oxidized form of nicotinamide, which serves as a component in two coenzymes required for energy metabolism:

1) NAD+ (nicotinamide adenine dinucleotide)

2) NADP+ (nicotinamide adenine dinucleotide phosphate).

NAD+ NADP+

Page 32: Vitamins Essential to Human Nutrition

Coenzymes NAD+ and NADP+ serve as electron acceptors (also called electron carriers) in important redox reactions in cells. By accepting a hydride ion H-, which means a gain of two electrons, both NAD+ and NADP+ are converted to their respective reduced forms, NADH and NADPH. (Reduction being a gain of electrons.)

Both NADH and NADPH can transfer (donate) 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. By shuttling two electrons to the electron transport chain, NAD+ and NADP+ are regenerated and can serve again as electron acceptors. The electron donor-acceptor cycle continues.

Page 33: Vitamins Essential to Human Nutrition

Sources of Vitamin B3:

Good sources of niacin are protein-rich foods such as meats, chicken, fish, eggs, dairy products, dried beans/peas and nuts.

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.

Our body can make niacin from tryptophan, but the synthesis is rather slow. To make 1 milligram (mg) of niacin, it takes about 60 mg of tryptophan. Tryptophan

Page 34: Vitamins Essential to Human Nutrition

4 Vitamin B5 (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.

OH

HO-CH2-CH—CH—C—NH-CH2CH2-C—OH

CH3

CH3

OOII II

I

I I

Pantothenic Acid

Vitamin B5 is required for the synthesis of coenzyme A. In fact, pantothenic acid is largely the “arm” of the coenzyme A molecule.

Page 35: Vitamins Essential to Human Nutrition

Coenzyme-A is constructed from three different molecules:

1) Pantothenic acid 2) Cysteine and 3) ATP

Coenzyme-A

Pantothenic acid

Cysteine

ATP

( also called co-A )

Page 36: Vitamins Essential to Human Nutrition

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.

Sources of Vitamin B5 (Pantothenic Acid):

Good sources of Vitamin B5 are numerous: including various meats, chicken, fish, eggs, milk, cheese, dried beans and peas, nuts of all sorts, whole-grain breads and cereals, avocados, bananas, carrots, corn, oranges, mushrooms and so many more.

Pantothenic Acid is truly a ubiquitous vitamin!

Page 37: Vitamins Essential to Human Nutrition

5 Vitamin B6 (Pyridoxine)

Vitamin B6 is actually a set of closely related molecules, including: pyridoxine, pyridoxal and pyridoxamine. All three are efficiently converted to pyridoxal phosphate, the bioactive form of vitamin B6.

Pyridoxine Pyridoxal

Pyridoxal phosphate

Pyridoxamine

Page 38: Vitamins Essential to Human Nutrition

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.

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

Amino acid metabolism

Breakdown of glycogen

Synthesis of globular proteins

Conversion of certain fatty acids

Page 39: Vitamins Essential to Human Nutrition

Sources of Vitamin B6:

A wide range of foods that are good sources of vitamin B6, include 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.

Interestingly, 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.

Page 40: Vitamins Essential to Human Nutrition

6 Vitamin B7 (Biotin) sometimes called Vitamin H.

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.

Biotin is a bicyclic compound formed from three molecules:

1) Thiophene ring

2) Ureido group

3) Valeric acid side chain1

2

3

Page 41: Vitamins Essential to Human Nutrition

Biotin serves as 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 in the catabolism (breakdown) of certain amino acids.

In humans, biotin participates in four different carboxylases:

1) Acetyl-CoA carboxylase (ACCase)

2) Propionyl-CoA carboxylase (PCCase)

3) Pyruvate carboxylase (PCase)

4) Beta-Methylcrotonyl CoA carboxylase (beta-MCCase)

Page 42: Vitamins Essential to Human Nutrition

How Biotin Works

Biotin present in foods is bound to specific proteins and must be released before it can be absorbed through the small intestine. Attaching biotin to another molecule is called "biotinylation." Action by proteolytic enzymes 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

Lysine

Page 43: Vitamins Essential to Human Nutrition

Although biocytin is easily absorbed in the small intestine, the body can only use biotin in its free form (i.e., without the lysine residue). The enzyme biotinidase cleaves biocytin into biotin and lysine. Biotin is then free to perform its duty as a coenzyme.

Sources of Vitamin B7 (Biotin):

Excellent sources of biotin include egg yolks, liver, milk, wheat germ and Brewer's yeast.

For those who would prefer other sources, biotin is found in fortified breads and cereals, rice, soybeans, peanuts, fish (e.g., herring and mackerel), mushrooms and bananas.

Page 44: Vitamins Essential to Human Nutrition

7 Vitamin B9 (Folic Acid) also called vitamin M.

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

Folate

Folate in Focus:Folate is recommended

for woman of childbearing age to help

prevent neural tube defects (NTDs) in the

developing fetus.

Page 45: Vitamins Essential to Human Nutrition

Folic acid (folate) is constructed from three molecules: 6-Methylpterin

Para-aminobenzoic acid (PABA)

Glutamic acid (glutamate)

6-Methylpterin PABA Glutamate

Page 46: Vitamins Essential to Human Nutrition

Tetrahydrofolate (THF): A Vital CoenzymeInside cells, folate is converted to its biologically active forms: 7,8-dihydrofolate (DHF) and 5,6,7,8-tetrahydrofolate (THF).

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 units.

THF5,6,7,8-tetrahydrofolate

Page 47: Vitamins Essential to Human Nutrition

B9

Folate is found in a variety of leafy green vegetables, bell peppers, oranges, liver, egg yolks, rice, barley and various legumes.

Folic acid is the synthetic form of folate and is added to a number of processed foods.

Folic Acid Alert: An interplay between vitamin B12 and vitamin B9

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.

Sources of Vitamin B9 (Folate):

Page 48: Vitamins Essential to Human Nutrition

8 Vitamin B12 (Cobalamin)

2The “Red” Vitamin

Called the “Red" vitamin, because it forms a dark red crystalline compound.1

Vitamin B12 is the only vitamin to contain the cobalt (Co3+) metal

ion, which by the way, gives it the red color. Vitamin B12, is also called cobalamin, cyanocobalamin and hydroxycobalamin. The coenzyme forms of vitamin B12 serve in a number of capacities.

Dr. Dorothy Crowfoot Hodgkin (a pioneer in the field of X-ray crystallography) elucidated the structure of vitamin B12 in 1955.

Page 49: Vitamins Essential to Human Nutrition

Although it looks quite complicated, vitamin B12 is really built from some basic parts: namely a nucleotide and a corrin ring.

The nucleotide, consisting of a nucleic acid, ribose sugar and a (PO4

3-) group, is attached to the corrin ring as are several methyl groups and amino acids.

The corrin ring (shown in blue) is made from four pyrrole groups. At the center of the corrin ring is the cobalt (Co) atom (shown in red).

Vitamin B12

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The four basic components of Vitamin B12:

Corrin Ring

Cobalt (Co) Amino AcidStructure

Nucleotide Structure

(1)

(2)

(3)

(4)

Page 51: Vitamins Essential to Human Nutrition

Attached to the cobalt Co atom is an R-group (shown in purple) used to represent the groups associated with the two cobalamins and the two coenzyme forms of vitamin B12.

If the R-group is cyanide (CN), then vitamin B12 is in the configuration of cyanocobalamin.

In the hydroxycobalamin form of vitamin B12, the R-group is given by the hydroxyl (OH) molecule. Vitamin B12

Page 52: Vitamins Essential to Human Nutrition

With respect to the two coenzyme forms of vitamin B12, R equals an adenosyl group in adenosylcobalamin and R equals a methyl group (CH3) in methylcobalamin.

The coenzyme forms of vitamin B12 serve a number of important functions. Adenosylcobalamin, for example, is the coenzyme for the enzyme methylmalonyl-CoA mutase, which in mitochondria converts methylmalonyl-CoA to succinyl-CoA.

Isomerization

Page 53: Vitamins Essential to Human Nutrition

This type of 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 then be metabolized to produce energy via the Kreb's cycle or used in the synthesis of fatty acids.

People with elevated methylmalonic acid levels in their blood or urine are not converting methylmalonyl-CoA to succinyl-CoA efficiently. They may, in fact, have a vitamin B12 deficiency.

Vitamin B12 in foods is bound to proteins and must be released before we can utilize it. Hydrochloric acid in the stomach does the job of releasing vitamin B12. The free vitamin, then binds to

glycoproteins called R-binders, forming a vitamin B12/R-binder complex, thus protecting it from destruction by hydrochloric acid.

Page 54: Vitamins Essential to Human Nutrition

A glycoprotein (i.e., sugar-containing protein) compound that has come to be known as the "intrinsic factor" is required for the proper absorption of vitamin B12. The intrinsic factor is secreted by the same parietal cells, which secrete hydrochloric acid into the stomach. The intrinsic factor binds to vitamin B12 (the "extrinsic factor") thus enabling its absorption through the small intestine and into the bloodstream.

The “Intrinsic Factor"

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 ideal, as 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 where the pH is much closer to neutral (pH ≈ 7).

Page 55: Vitamins Essential to Human Nutrition

Sources of Vitamin B12 (The “Red” Vitamin):

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

Vitamin B12 is found in organ and muscle meats, fish, shellfish, dairy products, eggs and in fortified foods such as breakfast cereals. 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.


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