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

Ph.D.)The Funny Man of HealthEducator

Entertainer

JU

G G LE

R

FOOD

Scientist

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

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.

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

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

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

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

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.

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

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

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-

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.

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

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+

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.

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

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.

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 )

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!

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

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

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.

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

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)

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

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.

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.

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

Para-aminobenzoic acid (PABA)

Glutamic acid (glutamate)

6-Methylpterin PABA Glutamate

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

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):

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.

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

The four basic components of Vitamin B12:

Corrin Ring

Cobalt (Co) Amino AcidStructure

Nucleotide Structure

(1)

(2)

(3)

(4)

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

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

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.

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).

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.