Circle a correct answer for each question: 1. The plasma membrane: a) is composed entirely of lipids. b) is mainly made up of proteins.

c) is approximately equal parts by weight of lipid and protein. d) is composed of equal parts of carbohydrates and lipids. 2. The plasma membrane: a) is largely impermeable to ions. b) is impermeable to water. c) has a uniform composition. d) forms a barrier to non-polar molecules.

3. ases such as oxygen and carbon dioxide cross the plasma membrane by: a) secondary acti!e transport. b) passi!e diffusion through the lipid bilayer. c) a specific gas transport proteins. d) primary acti!e transport.

". # cell secretes growth factors that ha!e a slow diffusion rate$ and interacting only with other cells in the immediate area is an example of %%%%%%%%%%%%%%% signaling. a) &xocrine b) 'ynaptic c) (aracrine d) #utocrine

). *ormones: a) are only secreted by exocrine glands. b) act only on neighboring cells. c) contain only polypeptides. d) are secreted into the blood.

+. *ormone receptors: a) ha!e a high affinity for their natural ligand. b) are always lin,ed to proteins. c) are lipids. d) are always located in the plasma membrane of their target cells. -. # typical characteristic of hormones that use the second messenger mechanism is that: a) they can not pass through the plasma membrane b) the receptor is located in the cytosol c) the receptor is located in the nucleus d) the receptor is not necessary e) the receptor binds to the hormone to allow it to enter the cell

.. /eceptors for steroid hormones can be found: a) b) c) d) e) in the plasma membrane in the cytosol in the mitochondria in the ribosomes in the olgi apparatus

0. 1hich of the of the following hormones use c#2( as second messenger3 a) b) c) d) e) 4nsulin Cortisol (rogesterone #ldosterone lucagon

15. 'ending a signal through the cell membrane can lead to the production of second messengers inside the cell. 1hich of the following can ser!e as second messengers3 a) c#2( b) Ca26 c) 4(3 d) 78 9nitric oxide: e) #ll of the abo!e

11. The endogenous T(ase acti!ity of -proteins ser!es to: a) 'timulate the acti!ity of en;ymes by producing energy. b) 'ynthesi;e c 2( as a second messenger. c) 'ynthesi;e T( as an energy source. d) *ydroly;e T( returning the protein to a pre-stimulated le!el of acti!ity. 12. 1hich of the following is 78T a typical e!ent associated with cell signaling3 a) b) c) d) #cti!ation of -proteins by exchanging <( for T( (roduction of the second messengers c#2( and 4(3 #cti!ation of protein ,inases 'timulation of apoptosis

13. The principal intracellular cation is: a) 7a6 9extracellular: b) =6 c) Cld) Ca26

True or >alse <ecide whether each of these statements is true or false$ and then explain why. 1. There is no fundamental distinction between signaling molecules that bind to cell-surface receptors and those that bind to intracellular receptors. >#?'& 2. The receptors in!ol!ed in paracrine$ synaptic$ and endocrine signaling all ha!e !ery high affinity for their respecti!e signaling molecules. >#?'& 3. #ll small intracellular mediators 9second messengers: are water soluble and diffuse freely through the cytosol. >#?'& 9c#2(@ 4(3 is water-soluble$ diacylglycerol is lipid-soluble: ". <ifferent isoforms of protein ,inase # in different cell types explain why the effects of cyclic #2( !ary depending on the target cell. >#?'& 9The effects !ary because of different substrate: ). The acti!ity of any protein regulated by phosphorylation depends on the balance at any instant between the acti!ities of the ,inases that phosphorylate it and the phosphatases that dephosphorylate it. 3

+. 4n contrast to the more direct signaling pathways used by nuclear receptors$ catalytic cascades of intracellular mediators pro!ide numerous opportunities for amplifying the responses to extracellular signals. 3

(roblems 1. Cells communicate in ways that resemble human communication. <ecide which of the following form of human communication are analogous to autocrine$ paracrine$ endocrine$ and synaptic signaling by cells. #. # telephone con!ersation 'ypnaptic 'ignaling A. Tal,ing to people at a coc,tail party (aracrine 'ignaling C. # radio announcement &ndocrine 'ignaling <. Tal,ing to yourself #utocrine 'ignaling 2. 'urgeon use succinylcholine$ which is an acetylcholine analog$ as a muscle relaxant. Care must be ta,en because some indi!iduals reco!er abnormally slowly from this paralysis$ with lifethreatening consequences. 'uch indi!iduals are deficient in an en;yme called pseudocholinesterase$ which is normally present in the blood$ where it slowly inacti!ates succinylcholine by hydrolysis to succinate and choline. 4f succinylcholine is an analog of acetylcholine$ why do you thin, it causes muscles to relax and not contract as acetylcholine does3 3. Compare and contrast signaling by neurons to signaling by endocrine cells. 1hat are the relati!e ad!antages of these two mechanisms for cellular communication3 7eurone >aster 'horter transmission *igh conc. @ low affinity &ndocrine cells 'lower <istance tra!elled is further ?ow conc. @ high affinity

". 1hy do signaling responses that in!ol!e changes in proteins already present in the cell occur in milliseconds to seconds$ whereas responses that require changes in gene expression requires minutes to hours3 ene expression needs transcription and translation$ hence ta,es more time

1hereas signaling responses is direct$ thus shorter duration needed ). *ow is it that different cells can respond in different ways to exactly the same signaling molecules e!en when they ha!e identical receptors3 4ts because of the different type of internal machinery to which the receptors are coupled to 9=inase$ /as$ Ba, pathway etc: +. 1hy do you suppose that phosphorylationCdephosphorylation$ as opposed to allosteric binding of small molecules$ for examples$ has e!ol!ed to play such a prominent role in switching proteins on and off in signaling pathways3 (hosphorylationCdephosphorylation switch protein onCoff faster 9e.g. serineCthreonineCtyrosine: 1hereas allosteric binding in!ol!es conformational change which requires more time 9calciumCcalmodulin: -. 1hen adrenaline 9epinephrine: binds to adrenergic receptors on the surface of a muscle cell$ it acti!ates a protein$ initiating a signaling pathway that results in the brea,down of muscle glycogen. *ow would you expect glycogen brea,down to be affected if muscle cells were inDected with non-hydroly;ed analog of T($ which cannot be con!erted to <(3 Consider what would happen in the absence of adrenaline and after a brief exposure to it. .. &xplain why cyclic #2( must be bro,en down rapidly in a cell to allow rapid signaling. 0. (hosphorylase ,inase integrates signals from the cyclic-#2(-dependant and Ca 26-dependent signaling pathways that control glycogen brea,down in li!er and muscle cells 9see figure 1:. (hosphorylase ,inase is composed of four subunits. 8ne is the protein ,inase that cataly;es the addition of phosphate to glycogen phosphorylase to acti!ate it for glycogen brea,down. The other three subunits are regulatory proteins that control the acti!ity of the catalytic subunit. Two contain sites for phosphorylation by (=#$ which is acti!ated by cyclic #2(. The remaining subunit is calmodulin$ which binds Ca26 when the cytosolic concentration rises. The regulatory subunits control the equilibrium between the acti!e and inacti!e conformations of the catalytic subunit. *ow does this arrangement allow phosphorylase to ser!e its role as an integrator protein for the multiple pathways that stimulate glycogen brea,down3 15. The outer segments of rod photoreceptor cells can be bro,en off$ isolated$ and used to study the effects of small molecules on !isual transduction because the bro,en end of each segment remains unsealed. *ow would you expect the !isual response to be affected by the following additions3 #. #n inhibitor of cyclic 2( phosphodiesterase. A. # nonhydroly;ed analog of T(. C. #n inhibitor of rhodopsine-specific ,inase.

>igure 1

>igure 2

11. <efine the terms ligand$ agonist$ and antagonist. i!e an example to illustrate how these molecules interact with the receptor. ?igand E naturally acquired endogenous chemical substance that bind to a receptor and induce natural response 9acetylcholine: #gonist E obtained chemical substance that mimic the action of ligand by binding to the same receptor and induce biological or natural response 9muscarine: #ntagonist E a substance that pre!ent the action of ligandCagonist by binding to the same receptor and do not produce any response 9atropine: 12. <escribe the structure and function of a gap Dunction. 'tructure E a pore in the plasma membrane$ created by + subunits of connexions which forms a connexion. 4ts protrude 1nm from the cell surface >unction E 13. 1hat is ?4CC 9?igand 4nduced Conformational Change: and gi!e an example to show how the change in ?4CC can bring about changes in the cellular acti!ities. ?4CC is a conformational change of the protein complex bring about by the binding of ligand to the receptor. e.g. Tyrosine ,inase acti!ation. -protein acti!ation 9changes of the FGH-complex: 1". <iscuss the mechanism of -protein acti!ation and inacti!ation in the normal indi!idual and in patient infected with cholera toxins. 1). <iscuss the acti!ation and inacti!ation of the !oltage gated 7a6 channel. i!e an example to show the importance of the !oltage gated 7a6 channel.