Dephosphorylation, regulation enzymatic activity

Within many tissues the enzymatic activities of the pyruvate and branched chain oxoacid dehydrogenases complexes are controlled in part by a phosphorylation -dephosphorylation mechanism (see Eq. 17-9). Phosphorylation of the decarboxylase subunit by an ATP-dependent kinase produces an inactive phosphoenzyme. A phosphatase reactivates the dehydrogenase to complete the regulatory cycle (see Eq. 17-9 and associated discussion). The regulation is apparently accomplished, in part, by controlling the affinity of the protein for... 

Sustained cytosolic Ca2+ overload usually results in a different route leading to cell death. It mainly relies on the activation of the calcium/calmodulin (CaM)-dependent phosphatase, calcineurin. Calcineurin-catalyzed dephosphorylation promotes apoptosis by regulating the activity of a number of downstream targets, including the pro-apoptotic Bcl-2 family member, Bad (Wang, et al., 1999), and transcription factors of the NFAT (nuclear factor of activated T cells) family (Rao, et al., 1997). There are also other Ca2+-dependent enzymes contributing to the apoptotic events, and they include several DNA-degrading endonucleases (Robertson, et al., 2000) and Ca2+-activated cystein proteases of the calpain family essential for the enzymatic activation of the crucial pro-apoptotic effectors (Altznauer, et al., 2004). 

The mammalian enzyme complex is even larger, containing almost 200 polypeptide chains to give a molecular weight of over 7 x 106. As well as the enzymatic activities described above, the mammalian complex contains two further enzymes which act as regulators by catalyzing phosphorylation/dephosphorylation of pyruvate decarboxylase in response to the metabolic demand the complex is activated by dephosphorylation when there is a need for the product acetyl-CoA and inactivated by phosphorylation when acetyl-CoA is not required. 

The molecular basis for regulation of enzymatic activity through phosphorylation and dephosphorylation has been established in many enzyme systems (29). The significance of these reactions in histones, ribosomal proteins and KNA polymerase is not known. In an attempt to establish the specificity of the cyclic AMP-dependent protein kinases, the structure of several substrates have been determined (30). The data indicate that the sequence around the phosphorylated serine residue all contain two basic amino acids separated by no more than two residues from the N-terminal of the susceptible serine (e.g. -Arg-Arg-X-Y-Ser-). 

Beg, Z.H. Stonik, J.A. Brewer, H.B. 3-Hydroxy-3-methylglutaryl coenzyme A reductase regulation of enzymatic activity by phosphorylation and dephosphorylation. Proc. Natl. Acad. Sci. USA, 75, 3678-3682 (1978)... 

All of these phosphatases except PP2C dephosphorylate tau in vitro and possibly in vivo (Gong et al., 2005). Their contribution in the regulation of tau dephosphorylation depends on their affinities for tau at different phosphorylation sites, then-specific enzymatic activities toward tau, and their relative abundance in the brain. 

As an enzymatic activity regulator, a-tocopherol inhibits protein kinase C activity, which is involved in cell proliferation and also plays a role in smooth muscle growth. a-Tocopherol has a stimulatory effect on the dephosphorylation enzyme, protein phosphatase 2A, which in turn cleaves phosphate groups from protein kinase C, leading to its deactivation, bringing the smooth muscle growth to a halt. This means that protein kinase... 

The activity of enzymes can be regulated by a number of means. The enzymes involved in the synthesis and hydrolysis of glycogen can be activated by phosphorylation, and deactivated by dephosphorylation. This is an example of covalent modification. Amino acids are synthesized by sequences of up to 15 separate enzymatically catalyzed reactions. If the end product is present in high concentrations, it combines with the first enzyme in the synthetic sequence and shuts it down. This is an example of feedback inhibition. Other kinds of feedback inhibition will prevent the synthesis of the enzyme itself by interfering with the transcription step producing messenger RNA. 

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