Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:6.4.1.2 (
acetyl-CoA carboxylase
)
2,876
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have previously demonstrated that de novo fatty acid synthesis predominantly occurs in later phases of
megakaryocyte
maturation. Therefore we have investigated the expression of fatty acid synthase (FAS) and
acetyl coenzyme A carboxylase
(
ACC
), key enzymes for fatty acid synthesis in megakaryocytes at different phases of maturation. Immature and mature megakaryocytes were isolated. Guinea pig-specific FAS and
ACC
cDNA probes were prepared by reverse transcriptase reaction-polymerase chain reaction (RT-PCR). The probes were used to assess the expression of mRNA for
ACC
and FAS by Northern blotting. The hybrids were quantitated by densitometry. Endogenous
megakaryocyte
ACC
was quantitated by virtue of its biotin content by Western blotting with streptavidin and enhanced chemiluminescence (ECL). The ratio of
ACC
mRNA between mature and immature megakaryocytes was 2.43 +/- 0.86, and the ratio of FAS mRNA was 0.50 +/- 0.13 (mean +/- SD, n = 4). The ratio of endogenous
ACC
in mature and immature megakaryocytes was 1.96 +/- 0.62 (n = 6). The study showed that the FAS mRNA was expressed in all phases of
megakaryocyte
maturation. However, both mRNA for
ACC
and endogenous
ACC
were demonstrated primarily in mature megakaryocytes. Thus de novo fatty acid synthesis in megakaryocytes may depend on the expression of
ACC
in mature cells. The expression of
ACC
occurs during the terminal phases of
megakaryocyte
maturation and may be a marker of
megakaryocyte
maturity.
...
PMID:The expression of acetyl coenzyme A carboxylase is related to megakaryocyte maturation. 763 91
Acetyl-CoA carboxylase
(
ACC
) catalyses the first step of de novo lipogenesis (DNL). Pharmacologic inhibition of
ACC
has been of interest for therapeutic intervention in a wide range of diseases. We demonstrate here that
ACC
and DNL are essential for platelet production in humans and monkeys, but in not rodents or dogs. During clinical evaluation of a systemically distributed
ACC
inhibitor, unexpected dose-dependent reductions in platelet count were observed. While platelet count reductions were not observed in rat and dog toxicology studies, subsequent studies in cynomolgus monkeys recapitulated these platelet count reductions with a similar concentration response to that in humans. These studies, along with ex vivo human
megakaryocyte
maturation studies, demonstrate that platelet lowering is a consequence of DNL inhibition likely to result in impaired
megakaryocyte
demarcation membrane formation. These observations demonstrate that while DNL is a minor quantitative contributor to global lipid balance in humans, DNL is essential to specific lipid pools of physiological importance.
...
PMID:De novo lipogenesis is essential for platelet production in humans. 3292 34
