Creatine Kinase

What is Creatine Kinase?

Creatine phosphokinase, or simply creatine kinase, is an enzyme found in many tissues which helps regulate the concentration of ATP (adenosine triphosphate) within a cell. In cells which need a lot of ATP, it is more economical to the cell to store the ATP as a less reactive molecule until it is needed. Thus, the phosphate group is transferred from ATP by creatine kinase to a creatine molecule. The end products are ADP (adenosine diphosphate), and PCr (phosphocreatine). This reaction is reversible, and when ATP is needed, it can easily be regenerated by the enzyme from the stored pool of PCr.

Function of Creatine Kinase

Creatine Kinase is found primarily in tissues which require a lot of ATP. Muscle cells, nerve cells, and even sperm cells are examples of highly active cells which contain large amounts of creatine kinase. This is because these cells must use a large amount of ATP to complete their work. Because of the nature of ATP, it must remain at certain concentrations to preserve the function of certain biochemical pathways. Therefore, the energy of ATP must be held in another place until it is needed. This place is PCr, which is simply a creatine molecule attached to a phosphate group.

The energy held in this bond can be efficiently and quickly converted by creatine kinase either to or from ATP. When there is too much ATP, creatine kinase functions to lower the concentration by converting ATP to ADP. It stores the extra phosphate on a creatine molecule, creating PCr. The pool of PCr in the cell is much larger than the amount of ATP. For this reason, it is considered a “fuel tank” or energy storage and utility system. As the mitochondria produce ATP through oxidative phosphorylation, the energy is transferred to PCr molecules, which are distributed to the cell.

These molecules do not affect the concentration of ATP, and therefore don’t interfere with cellular process. Other creatine kinase enzymes, which are attached to protein that require the energy from ATP, will use the pool of PCr to power whatever it is that they do. In this way, the production of ATP and the use of ATP are not directly tied to one another. The cell will usually only use high levels of ATP for a short amount of time, after which the system must return to normal. Using creatine kinase to maintain the “energy reservoir” is an efficient way to save up the ATP produced, without creating disruptive conditions for the cell. This is known as the PCr circuit. The chemical equation of the effects of creatine kinase can be seen below.

Structure of Creatine Kinase

Creatine kinase, like all proteins, is a specific chain of amino acids. When folded properly, this chain takes on a three-dimensional form, which gives it the ability to interact with certain molecules. The amino acids in creatine kinase are specific in that, when folded, they increase the interaction ability of creatine kinase with both creatine and phosphocreatine (PCr). Because the enzyme has a specificity for these molecules, it binds to them preferably over other molecules. Another site on creatine kinase is dedicated for interaction with ATP and ADP. As both molecules attach to the enzyme, it will either take a phosphate group from ATP and add it to creatine, or take a phosphate group from PCr and transfer it to ADP. The end result is either the creation or usage of ATP.

There are multiple types of creatine kinase, coded by different genes. While these forms of creatine kinase differ in their amino acid structure, their function remains similar. However, slight subtleties in function allow the creatine kinase to operate in different environments. For instance, mitochondrial creatine kinase, responsible for turning the ATP generated in the mitochondria into PCr for addition to the reservoir, must operate at different conditions than the creatine kinase in the cytosol. The pH balance and composition of solution are very different in the two areas of the cell.

Different cells even have different versions of creatine kinase, likely based on their function. The brain has a different form of creatine kinase than skeletal muscle. Smooth muscle and heart tissue use a combination of both types of creatine kinase. The different forms of creatine kinase all perform the same function, but under different conditions. These different forms are necessary to manage the energy reservoir in many different types of cell. In most cells, this reservoir of PCr is maintained at a concentration much higher than that of ATP. This makes it possible to do a lot of work.

Creatine Kinase Test

The different forms of creatine kinase make it a useful diagnostic took. Like other enzymes, creatine kinase is leaked into the bloodstream when a cell becomes damaged. If many cells are damaged at the same time, a detectable level of creatine kinase and other enzymes can be detected in the blood. Doctors can determine which form of creatine kinase is in the blood, which can give them clues as to which organs are being damaged.

A serum creatine kinase test can detect many conditions, such as a heart attack, muscle breakdown, and even autoimmune diseases which are attacking certain organs and tissues. After a heart attack, for instance, the creatine kinase level rapidly spikes in the blood. Further, a doctor can determine that it is a combination of muscular and brain creatine kinase. This is evidence that the heart has been damaged. Because the enzyme rapidly disappears from the blood, it can be used as an indicator to determine when a damaging event happened in the system. This can help find the cause of major events.

Quiz

1. A man enters the hospital with mild chest pain. The doctors test his blood serum, and find creatine kinase. Which of the following is a possible diagnosis?
A. Heart Attack
B. Indigestion
C. Lung irritation

Answer to Question #1

A is correct. Creatine kinase in the blood is a definite indication of tissue damage. Presented with chest pain, a heart attack is the obvious culprit. With indigestion and lung irritation, there is little to no tissue damage. Further, tissues like these have little to no creatine kinase, because they don’t use large amounts of energy.

2. What would happen if you changed the amino acid structure of creatine kinase?
A. It would function worse
B. It would function better
C. It would change function

Answer to Question #2

C is correct. The answer to this question lies in the organism the creatine kinase is present in. Changing the structure of creatine kinase may make the molecules it changes bind worse or better. Neither option is necessarily good, nor is either option bad. How the change affects the organism, and its ability to survive and reproduce, will determine the benefit or detriment of the change.

3. Why does creatine kinase keep PCr at higher levels than ATP?
A. PCr is like the energy reservoir molecule
B. The opposite is true
C. PCr can be used directly by enzymes for energy

Answer to Question #3

A is correct. When the first cellular organisms evolved, they likely did not need PCr. Their processes were simple, and they could produce all the energy they needed. As organisms evolved, however, there was an increasing need for large amounts of energy at once. This puts enormous strain on the process of oxidative phosphorylation, and it cannot keep up. Thus, organisms evolved the enzyme to store excess ATP as something else, until it is needed. This allowed them to continue using the ATP-concentration dependent pathways they had evolved, while increasing the amount of energy a cell could store.

References

• Bruice, P. Y. (2011). Organic Chemistry (6th ed.). Boston: Prentice Hall.


• Nelson, D. L., & Cox, M. M. (2008). Principles of Biochemistry. New York: W.H. Freeman and Company.


• Widmaier, E. P., Raff, H., & Strang, K. T. (2008). Vander’s Human Physiology: The Mechanisms of Body Function (11th ed.). Boston: McGraw-Hill Higher Education.

Creatine Kinase