title: The actions of cyclic AMP on biosynthetic processes are mediated indirectly by cyclic AMP-dependent protein kinase.
abstract: Adrenalin and glucagon inhibit glycogen, fatty acid and cholesterol synthesis by elevation of cyclic AMP, activation of cyclic AMP-dependent protein kinase and increased phosphorylation of the rate-limiting enzymes of these pathways. Here, we review recent evidence which indicates that inhibition of these biosynthetic pathways in muscle, adipose tissue and liver is much more indirect than has previously been supposed. In particular, cyclic AMP-dependent protein kinase does not appear to inhibit glycogen synthase, acetyl-CoA carboxylase and HMG-CoA reductase by phosphorylating them directly. It appears to achieve the same end result by inactivation of the protein phosphatases which dephosphorylate these regulatory enzymes in vivo, although this has only been established definitively in the case of glycogen synthesis.
authors.affiliation: Department of Biochemistry, University of Dundee, U.K.
authors.forename: P
authors.initials: P
authors.lastname: Cohen
authors.forename: D G
authors.initials: DG
authors.lastname: Hardie
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D005934:Glucagon / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D013566:Sympathomimetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D013566:Sympathomimetics; D005934:Glucagon; D002784:Cholesterol; D000242:Cyclic AMP; D006006:Glycogen Synthase; D011494:Protein Kinases