Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

25 Cards in this Set

  • Front
  • Back
Go to question 3
Go to question 3
Go to question 3
Go to question 3
What is the most common inborn error of B12 (cobalamin)? (Hint: what is observed biochemically?)
methylmalonic aciduria and homocysteinuria
What chromosome, locus, and gene related to methymalonoic aciduria and homocysteinuria?
1p34, cb1C, MMACHC
How was the gene located?
homozygosity mapping and haplotype analysis
Which mutations in MMACHC accounts for most diseased alleles and early onset?
271dupA and 331C
besides homocysteine metabolism (methionine synthase) , where else is cobalamin an important cofactor?
Methylmalonyl CoA -- Succinyl CoA... (In BCAA and fatty acid catabolism)
Which mitochondrial enzyme and reaction is the cobalamin dervative (AdoCbl) require for?
methylmalonyl CoA mutase… converts methylmalonyl CoA to succinyl CoA
What are the 6 major steps in the cobalamin pathway in cells, which are the potential source of inherited cobalamin transport and metabolism disorders? (Hint: what's the breakdown, why are they getting their B12?)
receptor mediated transport, endocytosis, TC II degradation in lysosome, release of Cbl into the cytoplasm, enzyme reduction of cobalt atom, cytosolic methylation (MeCbl) or mitochondrial adenylation to form AdoCbl.
What is the role of methylcobalamin (MeCbl… in the cytosol)?
it is a cofactor of methyltransferase in the conversion of Homocysteine to methionine
What is the role of adenosylcobalamin (AdoCbl in the mitochondria)?
it is a cofactor of mutase in the conversion of L-Methylmalonyl-CoA to Succinyl-CoA
What is TC II?
It is the tranport protein of cobalamin that enters cells via receptor mediated transport.
What is the methylmalonyl-CoA to Succinyl-CoA (Krebs) an entry port for? (hint: diet/protein breakdown… name amino acids, etc.)
cholesterol, odd-chain fatty acids, leucine, threonine
What are the 6 biochemical features of Cobalamin C disease? Which of the 6 is the definitive feature of the disease?
a) 1. megablastic anemia, 2. homocyteinuria, 3. hyperhomocysteinemia, 4. methylmalonic aciduria, 5. normal serum folate and B12… b) and 6 and the definitive feature: hypomethioninemia
Besides failure to thrive, feeding difficulties, dev and behavioral abnormalities, what are the clinical manifestations of Cobalamin C disease in early onset?
seizures, hypotonia, opthalmologic findings, renal impairment, marfanoid habitus
What are the clinical features of late onset cobalamin C?
acute neurologic decompensation, myelopathy, dementia or psychosis-like symptoms
What is the treatment of Cobalamin C disease?
hydroxycobalamin… there are others such as betaine, carnithine and folic acid supplementation but they are of little consequence
What is the inheritance pattern of Cobalamin C disease?
autosomal recessive
What are 2 prenatal diagnosis techniques of Cobalamin C disease?
1. Check for elevated levels of methylmalonic acid in amnionic fluid… 2. Appropriate uptake of both labelled propionate and methyl-FH4 by amniocytes
How would you treat the inherited metabolic diseases associated with the following? BCKA, homocysteinuria, familial rickets
BCKA -thiamin (B1)… Homocysteinuria-pyridoxine (B6) and Folic acid… Familial Rickets-Vit D
How was the cblC locus mapped to the 1p chromosome?
linkage analysis
How was the gene location pinpointed?
homozygosity mapping and haplotype analysis
What happened to the phenotype of cultured cells after the transduction of wild type MMACHC?
They functioned properly
Is MMACHC well conserved?
yes, bacterial cells have similar motiffs… ( TonB)
What are the uses for mutational analysis of MMACHC?
carrier identification and prenatal diagnosis