B vitamins (part II)

Today the other half of the B vitamins!

Excitement!

Pantothenic Acid (B5)Pantothenic acid, like the other B vitamins, plays a role in metabolism. It has two coenzyme forms or "active" forms, they are called coenzyme A (CoA) and acyl carrier protein (ACP). Like biotin, pantothenic acid is also cleaved in the small intestine into its active forms. CoA takes part in the transfer of acetyl groups as well as many other anabolic and catabolic fates such as into the TCA cycle, cholesterol and fatty acid oxidation. Specific examples include:

• oxidative decarboxylation
• fatty acid oxidation
• ketone body formation
• other carboxylic reactions (such as amino acid metabolism)
• synthetic reactions (like cholesterol synthesis)

ACP, pantothenic acid's other coenzyme takes part in fatty acid synthesis, and basically acts as a "chaperone" molecule to make fatty acids.

Sources of pantothenic acid include liver, meat, milk, whole grains and legumes. Clearly there are many sources of B5, so deficiency is rare. However it did occur, particular examples include during World War II characterized by soldiers getting "burning feet syndrome"... basically what it sounds like. Vitamin B5 has been implicated in a couple of studies to help with wound healing and lowering cholesterol.

Pyridoxine (B6)
This B vitamin has one coenzyme form, pyridoxal phospate (PLP). PLP participates in many important processes within the body. Playing a key role in amino acid metabolism, specifically transamination and decarboxylations. It can be found in many foods including fortified cereals, meats, grains and legumes. The important metabolic roles of B6 include:

• nervous system: synthesis of neurotransmitters (dopamine, serotonin, etc.)
• hormones
• glycogen breakdown
• red blood cell formation
• immune function

Vitamin B6 status can be tested using something called a "load test". This is when you give someone a large amount of a specific amino acid, in this case, tryptophan so that protein synthesis will be at a maximum and there will surely be enough left over for niacin synthesis (previously mentioned via the kyneurenine pathway). Since vitamin B6 must be present to convert tryptophan to niacin, a buildup of specific metabolites will be present signalling the B6 deficiency (kyneurinic acid will be present). Deficiency of this vitamin can result in nervous system problems including irritability, depression, confusion and sleeplessness, as well as dermatitis. These symptoms are similar to those of a riboflavin deficiency as both vitamins are implicated in similar pathways (ie kyneurinine!).

Vitamin B6 may interact with drugs such as anti-convulants and anti-tuberulosis medications. Large doses of B6 should be avoided in individuals taking these drugs, and a balance is key. In people not consuming these types of medication, toxicity is not typically an issue because like the other B vitamins, it is water soluble.

Vitamin B6 is implicated in many areas of health and diesease, including cardiovascular health, immune function, cognition, depression and PMS. There are many important roles of B6 and it is important to ensure it is being consumed in adequate amounts.

When thinking about protein synthesis and muscle growth, it may be important to consider the amount of B6 in the diet and whether supplementation may be needed to ensure adequate muscle gains. Often B vitamins are included in branched chain amino acid products.

Cobalamin (B12)

Vitamin B12 is the largest B vitamin, with the most complicated structure:

It has a cobalt molecule at the centre of its structure, and adsorption of this vitamin is a little more complicated than the others. Vitamin B12 is found in animal foods only, such as meat, dairy and fish. When consumed, vitamin B12 must undergo three stages in order to adsorbed.

1. gastric phase: digestion of the protein-bound B12 occurs, cobalamin is free to bind with "R" proteins found in the stomach, and together this bound form of B12 travels to the small intestine, at the same time, parietal cells in the stomach (that produce gastric acid) are producing intrinsic factor (IF)
2. luminal phase: the "R" proteins are digested and the B12 is free again, it now binds with IF
3. mucosal phase: the B12 and IF complex binds to a receptor in the ileum of the small intestine where adsorption occurs into circulation

In order for B12 to perform any metabolic functions, it must be converted into its coenzyme forms, methylcobalamin and adenosyl cobalamin. It can then play its part in red blood cell formation and neurological function.

B12 is a common deficiency in strict vegetarians and vegans, as well as the elderly. The capacity for production of IF decreases as we age so adsorption of B12 via the mucosa can be a problem. This can be corrected by supplementation (shots) that avoid the intestinal tract altogether.

Folate
Folate was named after leafy "foliage" because of where it is found. Mainly leafy, green vegetables but also corn, peas, beans, lentils and fortified foods. Folate when found  in food and in the body is termed "folate" however folate in supplements and fortified foods is called "folic acid". There is a big difference in the bioavailabilty of folate vs folic acid. Folate is much harder to absorb than folic acid even though this form still needs to be converted to folate within the body. Once adsorbed, it then needs to be converted to tetrahydrofolate (THF), its active form.

The calling card for folate is accepting and donating 1-carbon units, implicated in amino acid metabolism and nucleotide metabolism. There are many drugs that can compete with and inhibit folate adsorption. Folate deficiency can be due to diet or maladsorption, and shows similar symptoms to a B12 deficiency however instead of pernicious anemia, macrocytic anemia is observed. Deficiency can be tested with something called a "FIGLU" test. This is a load test using histidine, similar to the B6 tryptophan load test. In this case, histidine is given and the urinary metabolite FIGLU is tested to see if there is an impairment in the adsorption of folate.
Folate has an interesting history with the study of cancer. Some studies say that folate can increase cancer risk while other say that it can inhibit it (specifically colorectal cancers). There is potentially a timing and supplementation issue when it comes to folate. Lifelong folate supplementation (folic acid) is likely a good thing however with the presence of cancerous or precancerous lesions, extra folate should be avoided.

Folate is extremely important for the growth and development of neonates; if the mother does not have adequate folate in her diet from approximately 21-28 days post conception, spina bifida and neural tube defects are a big risk. This is problematic because this is often before the mother even realizes she is pregnant. It is a thought that all women of child-bearing age should consume folic acid supplements in order to ensure that this does not happen upon unknowingly conceiving.

This concludes my very long B vitamin post. I know it's a little ridiculous but it has helped me study :)