Adenylation, enzyme regulation

In brief adenylation involves the glutamine-dependent covalent attachment of up to 12 adenyl groups (one per subunit) to a tyrosyl residue of the enzyme subunit, by an adenyltransferase enzyme. The adenylated enzyme has a lower catalytic activity, an absolute requirement for manganese as the divalent cation and is considerably more susceptible to feedback inhibition than the unadenylated enzyme. Deadenylation is catalyzed by the same adenyltransferase as adenylation. Regulation as to which reaction the adenyltransferase catalyzes is modulated by a uridyltransferase which can... 

Adenylate kinase (AK) is a ubiquitous monomeric enzyme that catalyzes the interconversion of AMP, ADP, and ATP. This interconversion of the adenine nucleotides seems to be of particular importance in regulating the equilibrium of adenine nucleotides in tissues, especially in red blood cells. AK has three isozymes (AK 1,2, and 3). AK 1 is present in the cytosol of skeletal muscle, brain, and red blood cells, and AK 2 is found in the intermembrane space of mitochondria of liver, kidney, spleen, and heart. AK 3, also called GTP AMP phosphotransferase, exists in the mitochondrial matrix of liver and heart. 

Relaxation of smooth mnscles is controlled by the concentration of cyclic GMP in the muscle. This is regulated by the activities of the enzyme that forms cyclic GMP (i.e. gnanyl cyclase) and the enzyme that degrades cyclic GMP, that is, cyclic GMP phosphodiesterase (see Box 12.2). This is analogons to the enzyme system that regulates the concentration of cyclic AMP, by the activities of adenyl cyclase and phosphodiesterase ... 

Three major feedback mechanisms cooperate in regulating the overall rate of de novo purine nucleotide synthesis and the relative rates of formation of the two end products, adenylate and guanylate (Fig. 22-35). The first mechanism is exerted on the first reaction that is unique to purine synthesis—transfer of an amino group to PRPP to form 5-phosphoribosylamine. This reaction is catalyzed by the allosteric enzyme glutamine-PRPP amidotransferase, which is inhibited by the end products IMP, AMP, and GMP. AMP and GMP act synergisti-cally in this concerted inhibition. Thus, whenever either AMP or GMP accumulates to excess, the first step in its biosynthesis from PRPP is partially inhibited. 

A similar conformational change has been detected for calmodulin a heat-stable Ca2 +-binding protein. The field of Ca2+ research continues to expand noticeably, with articles focusing on calmodulin ll6). Calmodulin regulates the enzymatic activities of various enzymes such as adenylate cyclase and cyclic nucleotide phosphodiesterase. There are four Ca2+-binding sites in calmodulin, and the Ca2+ binding... 

The adenylate cyclases (AC) are a family of enzymes, which catalyze the synthesis of cyclic AMP (cAMP), from ATP. Cyclic AMP, a ubiquitous molecule in mammalian cells, plays a key role in controlling a vast number of biological processes, functioning as a major second messenger. The ACs are present in bacteria, where c-AMP plays a key role in the regulation of transcription in fungi, parasites and mammalian cells. The mammalians ACs (at least nine enzymes) are structurally unrelated to the bacterial ones consisting of 12 transmembrane helices and two cytoplasmic catalytic domains. They differ from each other in their... 

As mentioned earlier, the adenylate cyclase system is hormone sensitive and many hormones are capable of regulating the enzymes involved in either a stimulatory or an inhibitory manner, thus modulating... 

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