Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.1 (cytosine deaminase)
 747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein (apo-) B100 is the exclusive apolipoprotein of low density lipoproteins (LDL0, which transport most of the plasma cholesterol in humans. Mutations in apo-B100 can cause either hypocholesterolemia or hypercholesterolemia. Familial hypobetalipoproteinemia, which leads to hypocholesterolemia, has been shown to be caused by defects in the apo-B gene that terminate translation prematurely and result in the production of truncated proteins. The mutations responsible for the hypocholesterolemia have been either single nucleotide substitutions or deletions. Familial defective apo-B100, which leads to hypercholesterolemia, is caused by a point mutation in the receptor-binding domain of apo-B100. The mutation disrupts the binding of LDL to the LDL receptor, thereby disrupting LDL receptor-mediated catabolism and resulting in hypercholesterolemia. A variant form of apo-B, apo-B48, is also critical for lipoprotein metabolism. Apolipoprotein B48 is obligatory for the secretion of chylomicrons. It is formed from an RNA-edited apo-B mRNA in which codon 2153 has been converted from a CAA (glutamine) codon to a premature UAA (stop) codon. The first cytosine in this codon is deaminated to form uracil. The minimum nucleotide recognition sequence for the editing mechanism has been reported to be between 26 and more than 63 nucleotides surrounding codon 2153. The apo-B mRNA editing mechanism, which appears to be a cytosine deaminase, and its regulation are being actively investigated.
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PMID:Mutations and variants of apolipoprotein B that affect plasma cholesterol levels. 185 54

In humans, apolipoprotein (apo) B48 is synthesized in the intestine as an obligatory constituent of chylomicrons. Apolipoprotein B48 is identical to the amino-terminal 2152 amino acids (240 kDa) of apoB100 and is translated from an edited apoB mRNA in which codon 2153 has been converted from glutamine (CAA) to what is recognized as a premature stop codon (UAA). To determine whether the apoB mRNA editing in fact converts cytosine 6666 in codon 2153 to uracil, we incubated a synthetic apoB RNA containing 32P-labeled cytosines in an in vitro editing system prepared from rabbit enterocytes. The in vitro edited RNA was purified and digested to nucleoside 5'-monophosphates, which were analyzed on two-dimensional thin-layer chromatography. We found that the edited base co-migrated with authentic uridine 5'-monophosphate. Thus, cytosine 6666 is converted to uracil, most likely by a nucleotide-specific cytosine deaminase. To determine whether apoB mRNA editing occurs in cell lines that do not synthesize apoB, we stably transfected a high expression vector containing 354 base pairs of apoB sequence into 18 different cell lines. We found apoB mRNA editing activity in five osteosarcoma cell lines and one epidermoid cell line, none of which synthesizes any detectable apoB. Thus, apoB mRNA editing occurs in cell lines that do not synthesize apoB, which suggests that mRNA editing may be a common biological phenomenon in eukaryotic cells.
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PMID:Apolipoprotein B mRNA editing. Direct determination of the edited base and occurrence in non-apolipoprotein B-producing cell lines. 226 36