Saccharomyces cerevisiae is an important industrial cell factory and an attractive experimental model for evaluating novel metabolic engineering strategies. Many current and potential products of this yeast require acetyl coenzyme A (acetyl-CoA) as a precursor and pathways towards these products are generally expressed in its cytosol. The native S. cerevisiae pathway for production of cytosolic...

The Sir2 (silent information regulator 2) family of histone/protein deacetylases has been implicated in a wide range of biological activities, including gene silencing, life-span extension, and chromosomal stability. Their dependence on beta-NAD(+) for activity is unique among the known classes of histone/protein deacetylase. Sir2 enzymes have been shown to couple substrate deacetylation and be...

Macromolecule biosynthesis is required to duplicate cell components and support proliferation. Studies examining the nutrients used by cancer cells have focused on the contribution of glucose and glutamine carbon for biosynthesis, but the importance of other metabolic fuels is becoming apparent. Labeling of two-carbon units in newly synthesized lipids has been used to infer the nutrients that c...

BACKGROUND N-acetyl transferase (NAT) inactivates the pro-drug isoniazid (INH) to N-acetyl INH through a process of acetylation, and confers low-level resistance to INH in Mycobacterium tuberculosis (MTB). Similar to NAT of MTB, NAT2 in humans performs the same function of acetylation. Rapid acetylators, may not respond to INH treatment efficiently, and could be a potential risk factor, for the...

Reversible protein acetylation is a ubiquitous means for the rapid control of diverse cellular processes. Acetyltransferase enzymes transfer the acetyl group from acetyl-CoA to lysine residues, while deacetylase enzymes catalyze removal of the acetyl group by hydrolysis or by an NAD(+)-dependent reaction. Propionyl-coenzyme A (CoA), like acetyl-CoA, is a high energy product of fatty acid metabo...

Experimental evidence indicates that Ehrlich ascites tumor cells resistant to daunorubicin (DNR) have a higher active drug extrusion than do wild-type cells. In the present study, the possibility of circumventing this mechanism of resistance by addition of an analog of DNR, N-acetyldaunorubicin (N-acetyl-DNR), was investigated in vitro and in vivo. The affinity of N-acetyl-DNR was 7 times lower...

In an earlier paper (1) the writer described the preparation and isolation of three crystalline acetyl derivatives of pepsin. They were, "100 per cent active" acetyl pepsin in which the 3 or 4 primary amino groups of pepsin had been acetylated with less than 15 per cent change in the specific activity; "60 per cent active" acetyl pepsin whichcontained 6-11 acetyl groups per molecule; and "10 pe...

We have presented evidence that stimulation of pyruvate dehydrogenase, (PDH.) kinase activity by pyruvate or by acetyl-CoA is mediated through acetylation of lipoyl moieties (Cate, R. L., and Roche, T. E. (1978) J. Biol. Chem. 253,496-503). In accord with this indirect mechanism for the action of these effecters, we now find that the degree of stimulation of PDH, kinase increases with the level...

Current evidence suggests that the effects of lithium on metabolic and signaling pathways in the brain may vary depending on the specific clinical condition or disease model. For example, lithium increases levels of cerebral N-acetyl aspartate in patients with bipolar disorder but does not appear to affect N-acetyl aspartate levels in normal human subjects. Conversely, lithium significantly dec...

Protein acetylation has emerged as a means of controlling levels of mRNA synthesis in eukaryotic cells. Here we report that acetyl coenzyme A (acetyl-CoA) stimulates RNA polymerase II transcription in vitro in the absence of histones. The effect of acetyl-CoA on basal and activated transcription was studied in a human RNA polymerase II transcription system reconstituted from recombinant and hig...