Adenosine monophosphate, enzymes affecting

Activation of the postsynaptic receptor also leads to activation of the enzymes involved m the formation of so-called second messengers (see Box 42 for explanation of this and other terms used m this section). Best-known second messengers are cychc adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and cleavage products of phosphatidyh-nositol. These molecules are formed at the cell membrane and migrate into the cell where they affect the activity of other enzymes. 

Myoadenylate deaminase deficiency is a recessive disorder that affects approximately 1 -2% of populations of European descent, but appears considerably rarer in Asian populations. Myoadenylate deaminase, also called adenosine monophosphate (AMP) deaminase, is an enzyme that converts AMP to inosine monophosphate (IMP). Its deficiency results in excess AMP, which is lost by excretion with disturbances in energy generation. Symptoms of severe fatigue and muscle pain can result. 

Am. The hormones epinephrine and glucagon cannot penetrate cell membranes. They affect metabolic processes by binding to specific receptors on the membrane, which receptors in turn activate a specific enzyme bound to the inner membrane surface, adenylate cyclase. This enzyme converts ATP to cyclic AMP (cyclic adenosine monophosphate), or c-AMP. The presence of c-AMP activates another enzyme, protein kinase, which phosphorylates and activates phosphorylase kinase. Phosphorylase kinase phosphorylates phosphorylase b (inactive) to form phosphorylase a (active) which in turn cleaves glucose from glycogen by phosphorolysis to yield glucose-I-PO4. 

Posttranslational modification (PTM) with functional groups is a universal mechanism for diversifying the activities of proteins. PTMs can affect many properties of proteins, such as localization, activity status, interaction networks, solubility, folding, turnover, or stabUity. It is therefore of vital importance to accurately determine the identities of modified proteins, the modified amino acid residues, and the covalently attached group. This chapter describes the process of PTM identification using the adenylylation (i.e., the covalent transfer of an adenosine monophosphate (AMP)) of rat sarcoma related in brain (Rab) proteins hy Legionella pneumophila enzymes as an example. It also deals with the development of PTM-specific antibodies from synthetic peptides. This account underlines the importance of chemical biology in the elucidation of PTMs. 

The changes in the quaternary structure of rabbit-muscle phosphorylase b at 4 °C have been followed by measuring the reactivity of the thiol group. A slow, concerted transition between the two dimeric forms was shown to take place, the rate of which is affected by adenosine monophosphate. A phos-phopeptide containing 14 residues, including the phosphorylated serine residue, derived from the amino-terminus of rabbit skeletal-muscle phosphorylase has been shown to induce the enzymic properties of phosphorylase a in phosphorylases b and b (a modified form in which the phosphorylated site has been removed by limited digestion with trypsin). Thus, these enzymes become partially active in the absence of adenosine monophosphate. 

In addition to these we need to mention a small group of metabolites that belong structurally with the building blocks of nucleic acids but which have major metabolic functions that are quite separate from their relationship to nucleic acids. These are the adenosine phosphates two of these, adenosine 5 -triphosphate and adenosine 5 -diphosphate, participate in many metabolic reactions (more, indeed, than any other substance, aside from water) a third, adenosine 5 -monophosphate, participates in relatively few reactions but affects many enzymes as an inhibitor or as an activator. These names are cumbersome for everyday use and biochemists refer to them nearly aU of the time as ATP, ADP, and AMP, respectively. In animals, the ATP needed for driving all the functions of the cell is generated in small compartments of cells called mitochondria. For the purposes of this book we shall not need to know any details of how mitochondria fulfill their functions, but we do need to know that they exist, because we shall meet them again in a quite different context it turns out that in most organisms mitochondria contain small amounts of their own DNA, and this allows some special kinds of analyses. Adenosine, the skeleton from which ATP, ADP, and AMP are built, has a separate importance as one of the four bases that define the sequence of DNA. 

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