1. KAPITOLA 12 Interakce a regulace metabolismu vzájemné vztahy metabolických drah vzájemné vztahy metabolických drah uzlové body metabolismu uzlové body metabolismu regulační úloha hormonů regulační úloha hormonů

2. Metabolism of amino acids in the liver.

3. Insulin formation. Mature insulin is formed from its larger precursor preproinsulin by proteolytic processing. Removal of 23 amino acids (the signal sequence) at the amino terminus of preproinsulin and formation of three disulfide bonds produces proinsulin. Further proteolytic cuts remove the C peptide, leaving mature insulin, composed of A and B chains.

4. Fuel metabolism in the liver during prolonged starvation. After the depletion of stored carbohydrates, proteins become an important source of glucose, produced from glucogenic amino acids by gluconeogenesis (steps 1 through 4). Fatty acids imported from adipose tissue are converted into ketone bodies for export to the brain (steps 5 through 8). The broken arrows represent reactions through which there is reduced flux during starvation.

5. The mechanism that couples binding of epinephrine (E) to its receptor (Rec) with the activation of adenylate cyclase (AC). The seven steps are further discussed in the text. The same adenylate cyclase molecule in the plasme membrane may be regulated by a stimulatory G protein, Gs, as shown or an inhibitory G protein, Gi (not shown). Gs and Gi are under the influence of different hormones. Hormones that induce GTP binding to Gi cause inhibition of adenylate cyclase, resulting in lower cellular levels of cAMP.

6. Two intracellular second messengers are produced in the hormone-sensitive phosphatidyli- nositol system: inositol-1,4,5-trisphosphate (IP 3 ) and diacylglycerol. Both contribute to the activation of protein kinase C-IP 3 by raising cytosolic [Ca 2+ ], also activates other Ca 2+ - dependent enzymes. Thus Ca 2+ also acts as a second messenger. H represents the hormone, Rec receptor, PLC phospholipase C.

7. Role of voltage-gated and ligand-gated ion channels in passage of an electrical signal between two neurons. Initially, the plasma membrane of the presynaptic neuron is polarized, with the inside negative. This results from the action of the electrogenic Na + K + ATPase, which pumps three Na + outward for every two K + pumped into the neuron. 1)A stimulus to this neuron causes an action potential to move downward along its axon (white arrow). The opening of one voltage-gated Na + channel allows Na+ entry, and the resulting local depolarization causes the adjacent Na + channel to open, and so on. The directionality of movement of the action potential is ensured by the brief refractory period that follows the opening of each voltage-gated Na + channel. 2)When this wave of depolarization reaches the axon tip, voltage-gated Ca 2+ channels open, allowing Ca 2+ entry into the presynaptic neuron. 3)The resulting increase in internal [Ca 2+ ] triggers exocytosis of the neurotransmitter acetylcholine into the space between the neurons (synaptic cleft). 4)Acetylcholine binds to its specific receptor in the plasma membrane of the cell body of the postsynaptic neuron, causing the ligant-gated ion channel that is part of the receptor to open. 5)Extracellular Na + and K + enter through this channel, depolarizing the postsynaptic cell. The electrical signal has thus passed to the postsynaptic cell, and will move along its axon to a third neuron by this same sequence of events.

8. Calmodulin, the protein mediator of many Ca 2+ - stimulated enzymatic reactions, contains four high- affinity Ca 2+ - binding sites. (a)The binding of Ca 2+ induces a conformational change in calmodulin, allowing it to interact productively with the proteins that it regulates. One of the many enzymes regulated by calmodulin and Ca 2+ is Ca 2+ /calmodulin-dependent protein kinase, which phosphorylates Ser and Thr residues in target proteins. (b)A ribbon model of the structure of calmodulin, determined by x-ray crystallography. The four Ca 2+ - binding sites (red) are shown occupied by Ca 2+ (orange).

9. The insulin receptor consists of two a chains located on the outer face of the plasma membrane and two  chains that traverse the membrane and protrude on the cytosolic face. Binding of insulin to the a chains triggers autophosphorylation of Tyr residues in the carboxyl-terminal domain of the  subunits, which allows the tyrosine kinase domain to catalyze phosphorylation of other target proteins.