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Understanding the Adenylate Cyclase Pathway

Instructor: Darla Reed

Darla has taught undergraduate Enzyme Kinetics and has a doctorate in Basic Medical Science

In this lesson, we'll use easy-to-understand analogies, like armies and snowflakes, to learn about the enzyme, adenylate cyclase. In addition, we''ll explore how adenylate cyclase is used by the cell and why its regulation is so important.

What is Adenylate Cyclase?

We use energy to do a lot of things like jump rope, run and think. In our bodies, energy comes in the form of food. In our cells, energy comes in the form of adenosine triphosphate. Adenosine triphosphate (ATP) is a molecule cells use to make chemical reactions happen.

Structure of ATP
ATP contains adenosine and 3 phosphate groups

ATP is the reason our muscles work, our hearts beat and our brains function. But our cells use ATP as more than an energy source; when transformed by an enzyme into a completely different molecule, it can play an important part in cellular signaling. Adenylate cyclase (AC), or adenylyl cyclase, is the enzyme that changes ATP into cyclic adenosine monophosphate (AMP). Enzymes are proteins that speed up chemical reactions but are not used up during the process.

This enzymatic process is kind of like making snowflakes using paper and scissors. Think of the ATP as an unused piece of paper and the enzyme as the pair of scissors you can use to cut out a snowflake. When you're done cutting, the scissors can still be used to cut more paper just like an enzyme can cut bonds and is not used up when it functions.

AC Converts ATP to cAMP
AC converts ATP to cAMP

Cyclic AMP: Structure and Function

Cyclic adenosine monophosphate (cAMP/cyclic AMP), or c5'3'AMP as it is also known, plays a very important role in cellular signaling. It's responsible for putting many other molecules into motion. The term 'cyclic' is derived from its molecular structure. The phosphate group (PO4) forms bonds with the rest of the molecule that takes a circular or cyclic shape.

Cyclic AMP Structure
cyclic AMP structure

Imagine an army on horseback awaiting orders. It won't move until someone yells: CHARGE! cAMP is like a flood of armed horsemen following the order to charge. In the cell, changes in the amount of cAMP control hormone synthesis and secretion, the breakdown of triglycerides and glycogen, heart rate and water absorption.

As you might guess, if cAMP isn't regulated correctly by the cell, this lack of regulation may lead to some bad physiological consequences. Control of AC is very important so that cAMP is only formed in large quantities when required.

G-Proteins

AC is regulated by G-proteins, so called because they bind guanine phosphates. While there are many different types of G-proteins, we'll focus on the ones involved with AC. The G-proteins involved with AC are composed of three different pieces: alpha, beta and gamma.

G-Protein has Three Pieces
G-proteins typically have three pieces: alpha, beta and gamma

For the most part, the alpha piece of the G-protein interacts with AC. There are two types of G-proteins that can affect the AC: stimulatory G-proteins (Gs) or inhibitory G-proteins (Gi).

Remember that army on horseback awaiting orders? G-proteins hold the sealed envelope with the army's orders. In the case of the Gs, it holds the order to CHARGE! Gs activate AC, causing it to produce cAMP.

Gs Activates AC
Gs activates AC

Gi, on the other hand, holds the order to RETREAT! It prevents AC from forming cAMP.

Gi Prevents AC Activation
Gi prevents AC function

But who is giving the orders? The cell has receptors on its membrane that receive signals from the outside. Hormones, for example, can regulate the activity of AC through G-proteins. In this way, receptors are like the generals that pass on the sealed envelope to G-proteins.

Hormones Regulate G-Protein Activity and AC Function
Outside signals are the first step in activating AC

Alpha Pieces Bind Guanine Phosphates
G-protein alpha piece binds guanine phosphates

They are switched on and off by changes in the forms of the guanine phosphates they bind. When G-proteins are 'off', or inactive, the alpha piece binds guanine diphopshate (GDP).

Inactive G-proteins bind GDP
Inactive G-proteins bind GDP

When they are turned 'on', or activated by a receptor, guanine triphosphate (GTP) is bound to the alpha piece.

Active G-Proteins Bind GTP
Active G-proteins bind GTP

The alpha piece can change the GTP into GDP and in essence deactivate itself. Think of a motion sensor that turns on a light. When a receptor binds an outside signal, like a hormone, it's like someone jumping up and down in front of the motion sensor. The light flicks on, and the alpha piece binds GTP. After a while, when there's no movement, the light goes off on its own. The same thing happens with G-proteins: after a short while, the alpha piece automatically changes GTP into GDP.

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