• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Cobalamin deficiency results in severe metabolic disorder of serine and threonine

SaraM

Senior Member
Messages
526
http://www.ncbi.nlm.nih.gov/pubmed/11750758

I have threonine deficiency and a very low level of serine, and I have been taking a moderate daily dose of B12(1-5 g) for the last two years.



Cobalamin deficiency results in severe metabolic disorder of serine and threonine in rats.

Ebara S, Toyoshima S, Matsumura T, Adachi S, Takenaka S, Yamaji R, Watanabe F, Miyatake K, Inui H, Nakano Y.
Source

Department of Applied Biological Chemistry, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.
Abstract

Dietary cobalamin (vitamin B12; Cbl) deficiency caused significant increases in plasma serine, threonine, glycine, alanine, tyrosine, lysine and histidine levels in rats. In particular, the serine and threonine levels were over five and eight times, respectively, higher in the Cbl-deficient rats than those in the sufficient controls. In addition, some amino acids, including serine and threonine, were excreted into urine at significantly higher levels in the deficient rats. When Cbl was supplemented into the deficient rats for 2 weeks, in coincidence with the disappearance of the urinary excretion of methylmalonic acid (an index of Cbl deficiency), the plasma serine and threonine levels were normalized. These results indicate that Cbl deficiency results in metabolic disorder of certain amino acids, including serine and threonine. The expression level of hepatic serine dehydratase (SDH), which catalyzes the conversion of serine and threonine to pyruvate and 2-oxobutyrate, respectively, was significantly lowered by Cbl deficiency, even though Cbl does not participate directly in the enzyme reaction. The SDH activity in the deficient rats was less than 20% of that in the sufficient controls, and was normalized 2 weeks after the Cbl supplementation. It is thus suggested that the decrease of the SDH expression relates closely with the abnormalities in the plasma and urinary levels of serine and threonine in the Cbl-deficient rats.
 

AFCFS

Senior Member
Messages
312
Location
NC
I have a hard time understanding all the technical jargon in these articles. Are you saying that B12 caused the low levels of threonine and serine?

Not sure if this helps to answer your question. There are many "caveats" to all this; basically just an interpretative overview, and needed to string together a few sources to show the B12 as a co-factor for the BCAAs that seem to be indicated if Low Threonine/Low Serine.
(not all formatting is maintained)

Interpretive Guide for Amino Acids
Threonine
Low - can result in hypoglycemic symptoms, particularly if glycine or serine is also low. Supplement threonine/BCAAs.

High - excessive dietary intake or possible insufficient metabolism of threonine. The initial step here requires (vitamin B6) and zinc is needed to phosphorylate vitamin B6 to its active coenzyme form, so supplementation with vitamin B6 and zinc can be helpful.

Serine
Low - can lead to disordered methionine metabolism and deficits in acetylcholine synthesis. If simultaneous high threonine or phosphoserine, then need for vitamin B6, folate, and manganese is indicated.

High - when accompanied by low threonine, indicates glucogenic compensation and catabolism. Supplement threonine and BCAAs.

BCAAs: BRANCHED-CHAIN AMINO ACIDS Overview Information
Branched-chain amino acids are essential nutrients that the body obtains from proteins found in food, especially meat, dairy products, and legumes. They include leucine, isoleucine, and valine. “Branched-chain” refers to the chemical structure of these amino acids. People use branched-chain amino acids for medicine.

Branched-chain amino acids are used to treat amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), brain conditions due to liver disease (chronic hepatic encephalopathy, latent hepatic encephalopathy), a movement disorder called tardive dyskinesia, a genetic disease called McArdle's disease, a disease called spinocerebellar degeneration, and poor appetite in elderly kidney failure patients and cancer patients. Branched-chain amino acids are also used to help slow muscle wasting in people who are confined to bed.

Some people use branched-chain amino acids to prevent fatigue and improve concentration.

Athletes use branched-chain amino acids to improve exercise performance and reduce protein and muscle breakdown during intense exercise.

Healthcare providers give branched-chain amino acids intravenously (by IV) for sudden brain swelling due to liver disease (acute hepatic encephalopathy) and also when the body has been under extreme stress, for example after serious injury or widespread infection.

How does it work?

Branched-chain amino acids stimulate the building of protein in muscle and possibly reduce muscle breakdown. Branched-chain amino acids seem to prevent faulty message transmission in the brain cells of people with advanced liver disease, mania, tardive dyskinesia, and anorexia.

What are the important co-factors in taking BCAAs as supplements?
Before taking BCAAs tablets as dietary supplements, there are some things that you must remember to ensure that your body will be properly nourished. The following are some nutrients that must be factored in when using BCAAs supplement.

Zinc and Vitamin B6- Zinc is used to regulate insulin and its natural co-factor is vitamin B6. Vitamin B6 is necessary in amino acid metabolism. The transport of amino acids in the cells depends on the sufficient supply of this specific vitamin.

Chromium- This increases the effectiveness of insulin. It enhances the rate of protein synthesis in the body and also promotes intracellular uptake of the amino acids from the blood to the cells.
Biotin- An important member of the vitamin B family that plays a major role in the manufacture of glycogen and protein synthesis.

Vitamin B12- A vital water-soluble nutrient that is needed in protein metabolism and amino acids synthesis.
 

dbkita

Senior Member
Messages
655
Unless I am misinterpreting something, I think the abstract does not suggest a threonine / serine deficiency but a disorder in their metabolism and the reactions they are involved in, particularly the SDH conversion to pyruvate.

Since the SDH reaction is downgraded, the body builds up serine and threonine in the plasma and excretes it at high levels.

The people on here who have threonine or serine deficiency do not fit this pattern. They will have high serum / plasma and /or urine measurements. These animal tests suggest high measured levels of serine and threonine in serum and urine due to blocks in key reactions due to Cbl deficiency.

Seem like an interesting article though. Will have to see if I can track the actual document down at work.
 

AFCFS

Senior Member
Messages
312
Location
NC
Unless I am misinterpreting something, I think the abstract does not suggest a threonine / serine deficiency but a disorder in their metabolism and the reactions they are involved in, particularly the SDH conversion to pyruvate.
I think you are right. It is a bit interesting though that the B12 help adjust their metabolism (per the article), but may also be kind of an ancillary aid if they are low/deficient (per the other posting).
 
Messages
9
="SaraM, post: 266408, member:

I have threonine deficiency and a very low level of serine, and I have been taking a moderate daily dose of B12(1-5 g) for the last two years.

I have heard, I think on Heart-Fixer, that CBS+ mutations can cause a greater need for serine. Do you have a CBS mutation?
 
Messages
9
I'm CBS C699T +/+ and A360A +/- and I'm not sure if its a blessing or a curse like almost everyone else who knows there's more to it than what Yasko let on in the Autism book.

You seem to be saying they are meaningless, am I right?
I the gene your refering to impacted by them MTHFR?

I've only got MTHFR C677T +/- the other two on GeneticGenie are ok.. I just want to detox myself before I am likely to get CFS because my enzymes will all work better then post detox so I should avoid it. Although it'd be nice to know more about CBS so I have an idea as to whether I'm wasting money taking MeCbl ect. and having all my methyl inputs going down the "CBS drain".
 
Messages
15,786
You seem to be saying they are meaningless, am I right?
CBS A360A is completely meaningless. CBS C699T has an impact, but it's very mild and it's beneficial. Neither of them is capable of causing problems.

Is the gene you're referring to impacted by them MTHFR?
No, the CBS SNPs can impact the CBS gene. But those specific SNPs don't really have any meaningful impact.

Although it'd be nice to know more about CBS so I have an idea as to whether I'm wasting money taking MeCbl ect. and having all my methyl inputs going down the "CBS drain".
There's no CBS drain. That concept can be traced back to Yasko's inexplicable misinterpretation of a CBS gene study which did not involve those specific SNPs.

In that case, half of the entire gene was removed, which caused the enzyme activity to become up-regulated by a factor of 10 or more. But it is completely senseless to use that study to claim that CBS C699T somehow has the same effect, especially when actual research into C699T shows it is quite a mild variant.