Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Save to My Library
Look up keyword
Like this
0Activity
0 of .
Results for:
No results containing your search query
P. 1
Insufficiency of Folate and B12 in SMA Patients

Insufficiency of Folate and B12 in SMA Patients

Ratings: (0)|Views: 1 |Likes:
Published by Rama Shakti
Insufficiency of Folate and B12 in SMA Patients
Insufficiency of Folate and B12 in SMA Patients

More info:

Categories:Types, Research
Published by: Rama Shakti on Jun 26, 2013
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as RTF, PDF, TXT or read online from Scribd
See more
See less

06/26/2013

pdf

text

original

 
HHMI
HOWARD HUGHES MEDICAL INSTITUTE
MAY 25, 2001
RESEARCH NEWS
Vitamin Deficiency May WorsenMotor Neuron Disease
Gideon Dreyfuss
In the process of discovering a function for a common modification of proteins in the cell, researchers have found evidence that suggeststhatinsufficient amounts of folic acid and vitamin B12 in the diet mayexacerbatespinal muscular atrophy (SMA), a genetic disease that attacks motorneurons. The scientists are planning to collaborate with clinicians to explorewhetherthese vitamins might ameliorate the severity of symptoms in someSMApatients.In a research article published in the May 2001 issue of the journal
Molecular Cell
, Howard Hughes Medical Institute investigator Gideon Dreyfussandcolleagues at the University of Pennsylvania School of Medicine reportnewinformation about how the protein, "survival of motor neurons" (SMN),which is reduced or defective in people with SMA, attaches to otherproteinswith which it interacts.
"Insufficiency of folate and B12 in SMApatients is a real possibility and this could leadto under-methylation of proteins, even if onlyslightly. Given this possibility, it would seemprudent for these patients, in consultation withtheir physicians, to ensure that their dietincludes the recommended daily requirement of these vitamins."
- Gideon Dreyfuss
 
"SMN is a sort of master builder or chaperone that helps assemblemanylarge RNA-protein machines (RNPs) in the cell," said Dreyfuss. "Inparticular, it appears to help construct complicated molecularmachines thatare critical for the production of messenger RNA." Messenger RNAplays anessential role in ensuring that the information contained in DNA isproperlytranslated into functional proteins.SMA is the most common genetic cause of infant mortality, affectingaboutone in 6,000 newborns. The disease causes progressive muscleweakness,wasting, or atrophy as motor neurons degenerate. The severity of the disease ranges from milder forms, in which peoplecanlive into adulthood, to more severe forms that cause death a fewmonths afterbirth.SMA is caused by deletions of one of the two genes that code for theSMNprotein. Deletion of the gene reduces the level of SMN protein, whichcausesdamage to the nerve cells that serve major muscle groups.Loss of nerve stimulation causes muscles to atrophy and can resultparalysis.In their studies, Dreyfuss and his colleagues probed how SMN binds toitsmultiple target proteins in the cell. Using biochemical methods, theydetermined that SMN binds to regions of target proteins that are rich intheamino acids arginine and glycine. "When we tested binding of SMN totheseproteins directly
in vitro
, however, we found a surprisingly lowaffinity,"said Dreyfuss. "We then began to suspect that something else mustinfluencethe binding, because when we isolated the target proteins from cells,SMNbound to them avidly." To solve the mystery, Dreyfuss and his colleagues used the long-knownfactthat the arginines contained in many proteins are modified by theattachmentof two molecules called methyl groups. "Dimethylation of arginines is a
 
fairly common modification of proteins, especially RNA-bindingproteins,that had first been reported more than thirty years ago," said Dreyfuss."Butthe function of that modification was not known."By using synthetic peptides with (or without) the methylated argininesasfound in the cell, the researchers established that SMN did, indeed,bindtightly to its target proteins only when the arginines on those targetproteinswere dimethylated. "That alteration makes the modified proteininteract withanother protein -- in this particular case with SMN -- with much higheravidity," Dreyfuss said. The alteration of the arginines quite likelychangesthe shape of the protein's surface, making it fit SMN more snugly, heexplained. The finding -- which solves a three-decade-old scientific mystery --providesa new research pathway for studying how proteins attach to oneanother andmight also have clinical implications for people who have SMA, saidDreyfuss."These SMN target proteins obtain their methyl groups from a methyldonorcalled,
S
-adensylmethionine, which itself depends on folate andvitamin B12as part of its metabolic pathway," said Dreyfuss. Humans cannotproduce orstore folate and B12, so they must obtain those vitamins through theirdiet."The thought is that SMA patients, who are already compromised intheirlevels of SMN, might be more severely affected if they are alsosuboptimal intheir levels of protein methylation," said Dreyfuss."Insufficiency of folate and B12 in SMA patients is a real possibility andthiscould lead to under-methylation of proteins, even if only slightly," hesaid."Given this possibility, it would seem prudent for these patients, inconsultation with their physicians, to ensure that their diet includes therecommended daily requirement of these vitamins."Dreyfuss is planning to collaborate with neurologists Thomas Crawfordof 

You're Reading a Free Preview

Download
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->