Cyclic AMP dependent Protein-Kinase (PKA)

cAMP exerts its effects mainly by activating cyclic AMP-dependent protein kinase (PKA).This enzyme catalyses the transfer of terminal P group from ATP to specific serine or threonines of selected target proteins.

In inactive state, PKA consists of two catalytic & two regulatory subunits ‘C2 R2’ with regulatory units blocking catalytic centers of catalytic units.The binding of cAMP to the regulatory subunit (2 on each regulatory subunits) alters their conformation, causing them to dissociate from the complex.The released catalytic subunits are thereby activated to phosphorylate specific substrate protein molecules.

TURN ON

Initially the G-protein a subunit has bound GDP, and the a, b, & y subunits are complexed together.

• Hormone binding to a 7-helix receptor (GPCR) causes a conformational change in the receptor that is transmitted to the G-protein. The nucleotide-binding site on G-a becomes more accessible to the cytosol. G-a releases GDP and binds GTP. (GDP-GTP exchange)


• Substitution of GTP for GDP causes another conformational change in G-a. Ga-GTP dissociates from the inhibitory b,y subunit complex, and can now bind to and activate Adenylyl Cyclase.


• Adenylyl Cyclase, activated by the stimulatory Ga-GTP, catalyzes synthesis of cAMP.


• Protein Kinase A (cAMP-Dependent Protein Kinase) catalyzes phosphorylation of various cellular proteins, altering their activity.
  

TURN OFF

• Ga hydrolyzes GTP to GDP + Pi (GTPase). The presence of GDP on Ga causes it to rebind to the inhibitory b,y complex. Adenylate cyclase is no longer activated.


• Phosphodiesterase catalyzes hydrolysis of cAMP to AMP.


• Receptor desensitization occurs. This process varies with the hormone. Some receptors are phosphorylated via specific receptor kinases. The phosphorylated receptor may then bind to a protein arrestin, that promotes removal of the receptor from the membrane by clathrin-mediated endocytosis.


• Protein Phosphatase catalyzes removal by hydrolysis of phosphates that were attached to proteins via Protein Kinase A.

THE RIGHT PERSON??

Many people believe (because we have long been told from movies) that there is a person who fits our specific requirements and it is just a case of finding him. Some people probably do. But most people in happy, stable relationships have partners who meet some of the important qualities rather than all of their requirements.

Supportive acceptance to each other’s shortcomings, real or perceived is the foundation of a relationship. After all nobody is perfect (Except Of Course “ME”). By rejecting any person you meet, who does not immediately appear absolutely right for you, you are missing out on knowing some wonderful people, one of whom could turn out to be “The One” for you.

Finding the “Right Person” is about finding yourself, knowing what you are and what is important to you. If fantastic looks are important to you that is fine but ultimately a person who makes you happy from day to day is more of an asset than the handsome hunk you would have preferred.

Many people are afraid of intimacy. This fear is closely related to the fear of abandonment and rejection. Perhaps these people think on a subconscious and unintentional level, that once he gets to know you he won’t like you. So you reject him before he can reject you. Take a hard, honest look at yourself and ask is this what you want. Do not think I’m not worthy. You should try to reinvent yourself and your place in the world. You should become whole before becoming somebody’s half.

Always feel confident about yourself. Love yourself. If you do not love yourself, the vibes you give off repel other person from you and it is a great inhibitor to being liked by others. Do not have any inferiority complex. Always believe in yourself. Remember it is you and your feeling that is important in your life.

ABOUT LOVE.....

It takes only a minute to get crush on someone, an hour to like someone and a day to love someone. We never find out from where love begins and where it ends. If love has its beginning and end then that’s not love, that’s only as attraction. If something is liked, but not loved it’s just an attraction. True love can only be felt, not seen.

It hurts to love someone and not to be loved in return, but what is more painful is to love someone but never find courage to let that person know how you feel.

Love is that when you take away the feelings, the passion and the romance in a relationship and find out you still care for that person. Sad things in life is when you meet someone who meant a lot to you but only to find out in the end that it was never meant to be yours and you just have to let it go.

Sometimes we find our heart broken, feelings shattered by those person whom we have once believed and trusted on. Maybe God wants us to meet a few wrong people before meeting the right one, so that when we finally meet the right person. We will know now to be grateful for that gift. When the door of happiness closes another door opens but we often look so long as the closed door that we don’t see the one, which has been opened for us.

Giving all your love to someone is never an assurance that he/she will also love you. Don’t expect love in return; just wait for it to grow in theirs heart. But if it doesn’t still be content it grew in yours.

A thought for today : FRIENDSHIP

Life means missing expected things and facing unexpected things. When you are right, no one remembers, but when you are wrong, no one forgets. This is life.

Keep the lamp of friendship burning with oil of love because sun rises in east and sets in west. But friendship rises in heart and sets after death. Do remember ur friends. They are really special in life.

Why Do Women Make Better Naggers?

Most women have the brain organization to out-talk and out-nag any man on the planet. A female brain is organized for multi-tracking—she can juggle four or five balls in the air at the same time. She can run a computer program while talking on the telephone plus listen to a second conversation behind her, all the time drinking a cup of coffee. She can talk about several unrelated topics in the one conversation and uses five vocal tones to change the subject or emphasize points. Men can identify only three of those tones. As a result, men often lose the plot when listening to women talk.

Multi-tracking can even occur in a single sentence—

Bill: "Is Sue coming over for Christmas?"

Debbie: "Sue said she'll come depending on how things go with carpet orders which have slowed down because of the economy and Fiona may not come because Andrew has to see a specialist and Nathan has lost his job too so he has to get a new one and Jodi can't get time off work—her boss is so tough!—so Sue said she could come down early and we could go dress shopping for Emma's wedding and I thought that if we put her and Len in the guest bedroom we could ask Ray to arrive early so . . ."

Bill: "Does that mean 'yes' or 'no'?"

Debbie: "Well, it also depends on whether Diana's boss Adrian will give her time off work because his car is off the road and she has to . . ." etc., etc.

Bill thought he had asked a simple question and he would have been happy with a simple answer like "yes" or "no." Instead, he got a multi-tracked answer involving nine different subjects and eleven people. He feels frustrated and goes outside to water the garden.

Male brains are organized for mono-tracking. They can only concentrate on one thing at a time. When a man opens a map, he turns the radio off. If she talks with him when he's driving on a rotary, he'll miss his exit and then blame her because she was talking. When a telephone rings he asks everyone to be quiet so he can answer it. For some men, often in the most powerful positions, it can even prove hard to walk and chew gum at the same time.

Men's brains are mono-tracked. They can't make love and answer questions on why they haven't taken out the garbage at the same time.

One of the big problems for men is when multi-tracking happens during the nagging process. It's all too much for him so he simply shuts off. This goes on to begin a vicious cycle of the nagger increasing her volume and the strength of her accusations or claim to entitlement while the victim retreats further behind his barrier, often to the point of putting physical distance between himself and the nagger. Leaving the scene may not always be possible and the pressure will build up to a point where the victim will strike back resulting in a bitter argument. Sometimes that could even spill over into physical violence.

From the book “Why man don’t have a clue and woman always need more shoes?” By Barbara Pease.