Adenosine monophosphate liver enzyme

Activation of Gs or Gi proteins results in stimulation or inhibition, respectively, of adenylyl cyclase which catalyses the formation of cyclic adenosine monophosphate (cAMP) from ATP The cAMP binds to protein kinase A (PKA), which mediates the diverse cellular effects of cAMP by phosphorylating substrate enzymes, thereby increasing their activity. Among the responses mediated by cAMP are increases in contraction of cardiac and skeletal muscle and glycogenolysis in the liver by adrenaline (epinephrine). Because a single activated receptor can cause the conversion of up to 100 inactive Gs proteins to the active form, and each of these results in the synthesis of several hundred cAMP molecules, there is a very considerable signal amplification. For example, adrenaline concentrations as low as 10-10 M can stimulate the release of glucose sufficient to increase... 

Glucagon appears to exert its effects on liver cells by a classic adenyl cyclase-cyclic adenosine monophosphate (cAMP) second messenger system (see Chapter 4).93 Glucagon binds to a specific receptor located on the hepatic cell membrane. This stimulates the activity of the adenyl cyclase enzyme that transforms adeno-... 

For lipogenesis, glucose 6-phosphate is converted through glycolysis to pyruvate. Key enzymes that regulate this pathway in the liver are phosphofructokinase-1 (PFK-1) and pyruvate kinase. PFK-1 is aliosterically activated in the fed state by fructose 2,6-bisphosphate and adenosine monophosphate (AMP) (see Fig. 36.1). Phosphofructokinase-2, the enzyme that produces the activator fructose 2,6-bisphosphate, is dephosphorylated and active after a meal (see Chapter 22). Pyruvate kinase is also activated by dephosphorylation, which is stimulated by the increase of the insulin/glucagon ratio in the fed state (see Fig. 36.1). 

Phosphofructokinase 2 (PFK-2) is negatively regulated by phosphorylation in the liver (the enzyme that catalyzes the phosphorylation is the cyclic adenosine monophosphate [cAMP]-dependent protein kinase). However, in skeletal muscle, PFK-2 is not regulated by phosphorylation. This is because the skeletal muscle isozyme of PFK-2 lacks the regulatory serine residue, which is phosphorylated in the liver. However, the cardiac isozyme of PFK-2 is phosphorylated and activated by a kinase cascade initiated by insulin. This allows the heart to activate glycolysis and to use blood glucose when blood glucose levels are elevated. 

Some information is available on the chemical differences between members of a pair of analogous enzymes. Thus the enzyme that hydrolyses cyclic adenosine monophosphate (cAMP) has been shown to have different molecular composition when specimens from different mammalian tissues were compared (Weiss and Fertel, 1977). Relevantly, pyruvate kinase from healthy liver (L), kidney (K), and muscle (M) of the rat gave inhibitory ratios (L K M) of 1 7.6 6 with 3 -methoxy-ADP, of 1 1.2 7.1 with 8-ethylamino-ADP, and 3 2 1 with methyl-(AT-acetyl-ci) methylaminobutyl)-ADP (Hai, Abo and Hampton, 1982). Similarly, small changes in the substituents inserted into pyrazolo-[1,5-fl]-l, 3,5-triazine 4.53) bring about an inhibition of cAMP phosphodiesterase in different tissues from this list bovine brain, bovine heart, or rabbit lung (Senga etal., 1982). 

Conditions for the assay of liver phosphorylases a and b have been reviewed, and procedures were suggested for the estimation of these enzymes. For example, both forms can be estimated at pH 6.5 in the presence of 1% glycogen, 0.05M-D-glucose 1-phosphate, and 0.15M-sodium fluoride. This assay can be made specific for phosphorylase a by the addition of either caffeine or maleate. The total activity is best measured in the presence of ImM-adenosine monophosphate and 0.5M-sulphate. 

Fig. 2.4 Hormone reaction cascade triggered by the arrival of the hormone molecule adrenalin (1) at a transmembrane receptor (2) on the surface of a liver cell. The receptor activates the membrane-anchored stimulatory G-protein (Gs) which carries the message to the effector, adenylate cyclase. This enzyme converts ATP to the most widespread second messenger molecule, cyclic adenosin monophosphate (cAMP). cAMP diffuses through the cell and triggers an enzyme cascade which ultimately leads to the degradation of the storage carbohydrate glycogen and the release of glucose from the cell.

Tissue electrodes [2, 3, 4, 5, 45,57], In these biosensors, a thin layer of tissue is attached to the internal sensor. The enzymic reactions taking place in the tissue liberate products sensed by the internal sensor. In the glutamine electrode [5, 45], a thick layer (about 0.05 mm) of porcine liver is used and in the adenosine-5 -monophosphate electrode [4], a layer of rabbit muscle tissue. In both cases, the ammonia gas probe is the indicator electrode. Various types of enzyme, bacterial and tissue electrodes were compared [2]. In an adenosine electrode a mixture of cells obtained from the outer (mucosal) side of a mouse small intestine was used [3j. The stability of all these electrodes increases in the presence of sodium azide in the solution that prevents bacterial decomposition of the tissue. In an electrode specific for the antidiuretic hormone [57], toad bladder is placed over the membrane of a sodium-sensitive glass electrode. In the presence of the antidiuretic hormone, sodium ions are transported through the bladder and the sodium electrode response depends on the hormone concentration. 

This enzyme is an alkaline phosphomonoesterase that catalyzes the hydrolysis of nucleoside 5 -monophosphates (e.g., adenosine-5 -monophosphate and inosine-5 -monophosphate). It appears to be distributed widely in the body tissues and to be mainly a membrane-bound enzyme, but it is also found in the cytoplasm, lysosomes, and other subcellular organelles. In the liver, the enzyme is located on the bile canicular membrane and on other cells, including the sinusoidal cells, leading to its use for the detection of hepatobiliary injury (Goldberg 1973 Dooley and Racich 1980 Carakostas, Power, and Banerjee 1990 Sunderman 1990). The enzyme measurement has largely been discarded in clinical medicine however, more recently, the 5 -NT enzymes have been implicated in the inhibition of antiviral nucleosides, so interest may be revived (Hunsucker, Mitchell, and Spychala 2005). 

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