Vitamin B12 and Disease

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Vitamin B12 and Disease

_http://coolinginflammation.blogspot.com/_

(http://coolinginflammation.blogspot.com/)

 

Vitamin B12 and the associated amino acids methionine and cysteine are

essential to avoid specific symptoms of anemia and the deleterious effects of

inflammation.

 

Vitamin B12, cobalamin, cannot be made by the human body and requires a

protein secreted by stomach cells, intrinsic protein, for uptake from the diet

or

from gut bacteria. In the absence of dietary B12, individuals can develop

pernicious anemia. Since vitamin B12 is used by enzymes involved in nucleic

acid synthesis, the rapidly dividing cell of the blood show the first symptoms.

Another feature of pernicious anemia is the production of autoimmune

antibodies against gastric intrinsic protein. This means that even if the diet

is

supplemented with vitamin B12, the anemic patient would show no improvement.

Historically, the cure was beef liver juice containing B12 already bound to

intrinsic factor.

 

I enjoyed learning about the autoimmune aspect of pernicious anemia, because

when I examined the sequence of the human intrinsic factor, I found the

expected pairs of basic amino acids that I associate with strong heparin

binding,

uptake and presentation of allergens. Moreover, the structure of the protein

has not yet been determined and intrinsic protein has been called one of the

intrinsically unstructured proteins. Proteins with many heparin-binding

domains frequently only have a stable shape when bound to heparin. I would

predict that pernicious anemia results when intrinsic factor is presented to

the

immune system as a result of inflammation of the stomach or intestines.

Subsequently, anti-intrinsic protein antibodies block B12 uptake. Pernicious

anemia

is commonly associated with pathogen attack on stomach tissue by Helicobacter

pylori, the stomach ulcer and gastric cancer bacterium. Treatment for B12

deficiency has to bypass the required binding to intrinsic factor and uses

injection or inhalation of B12 supplements.

 

There is also a group of proteins that bind to B12 in the human body and

apparently block uptake of B12 by pathogens. These proteins are called “R

binderâ€

proteins and are present in the body in the same pattern as lactoferrin, an

antibacterial protein that binds iron, another critical limited nutrient

needed by pathogens.

 

B12 is used by enzymes to hold methyl groups as the groups are moved from

one place to another on a substrate molecule. So B12 is needed to donate a

methyl group to homocysteine to regenerate the amino acid methionine. In the

absence of B12, homocysteine accumulates in the blood and begins to react with

the cysteines and lysines of proteins. It is particularly reactive with enzyme

active sites and inactivates lysyl oxidase, which cross-links collagen and

elastin that are needed for the integrity of heart and smooth muscle.

 

Inability to regenerate methionine also eliminates the essential functions

of its derivative S-adenosylmethionine, SAM, which is involved in polyamine

synthesis and cysteine synthesis. Cyseine is an essential amino acid that is

one of the three amino acids in glutathione, the major antioxidant of cells.

Thus, a methionine deficiency can result in severe oxidative stress and

inflammation.

 

Disruption of normal nutrition, gut flora and uptake can result in

deficiencies of vitamin B12, methionine and cysteine, with a subsequent cascade

of

oxidative events leading to inflammation, autoimmunity and degenerative

diseases. It seems likely that a similar scenario could be associated with loss

of

physical activity and muscle mass (sarcopenia) of aging. As the older

person’s

energy requirements decrease, less food will be required, but the composition

will need to be adjusted carefully to maintain a healthy gut flora and avoid

vitamin and amino acid deficiencies. I would not be surprised if the diets

of most older people are grossly inadequate to avoid deleterious chronic

inflammation. Poorly managed inflammation could account for most of the

symptoms

of aging and its associated degenerative diseases.

 

On a closing note, alcohol consumption has be associated with both hangovers

and decreased risk of cardiovascular disease. The hangovers are due to

alcohol conversion to acetaldehyde. Reaction of acetaldehyde with cysteine may

be

both a cure for hangovers and a partial explanation for increased longevity

associated with moderate consumption of alcohol. Moderate and consistent

alcohol consumption may cause an increase in cysteine storage as a compensation

for losses due to alcohol intake. If the alcohol adapted person has higher

stores of cysteine, there may be a simultaneous increase in cellular

glutathione

with a corresponding decrease in oxidative stress and inflammation. Decrease

in inflammation is associated with increased longevity. Supplementation with

cysteine prior to alcohol consumption eliminates a hangover and may also make

you live longer!

 

 

 

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