What is PKCepsilon?
October 5, 2007 2:10 PM Subscribe
What is PKCepsilon? What is it? Is it made by the body? Is the generation of this nutritional?
A recent news article that appeared on Slashdot discusses PKCepsilon. This is related to type 2 diabetes. I've looked high and low for a layman's explanation, but all I've found are scientific papers on it. Working my hardest, I can rarely get through the first two paragraphs before I am lost.
Article: http://www.abc.net.au/news/stories/2007/10/04/2050657.htm
A recent news article that appeared on Slashdot discusses PKCepsilon. This is related to type 2 diabetes. I've looked high and low for a layman's explanation, but all I've found are scientific papers on it. Working my hardest, I can rarely get through the first two paragraphs before I am lost.
Article: http://www.abc.net.au/news/stories/2007/10/04/2050657.htm
OK, I'll have a go at it. In small steps:
PKCepsilon = Protein Kinase C epsilon.
So what's a protein kinase? It's an enzyme, which means that it is a protein that catalyzes a chemical reaction.
Kinases are enzymes that put a phosphate group onto something else (that's the chemical reaction).
"Protein kinase" means that the target is another protein, as opposed to some other type of molecule.
There are lots of different kinases, which is why they are given letters (A, B, C) so you know which one you're referring to.
Epsilon means that we've found subtle differences in a sample of what used to be thought of as a single unique enzyme (protein kinase C). If you purify protein kinase C from a piece of, say, liver tissue you will get a solution that contains thousands or millions of molecules. If you look very carefully in this population of molecules for these small differences you can see them. Presumably there are alpha, beta, gamma, and delta forms of protein kinase C as well as the epsilon form.
So let's come up for air and consider your macro-scale questions. PKCepsilon is definitely made by the body. It is present in fairly small amounts since it only has to catalyze a chemical reaction so it could not be considered nutritional (if I'm interpreting your question correctly - by "nutritional protein" I assume you mean the stuff that makes up the bulk of the proteins we eat, like the muscle proteins of red meat).
The generation of all proteins by the body consumes energy and raw materials (amino acids), so when your body makes the proteins it needs you could sorta consider it "anti-nutritional" since it's using up some of the energy and raw materials you get from the food you eat.
The article you linked to discusses the idea of knocking out this enzyme so it can't catalyze its chemical reaction (moving that phosphate group onto another protein). This reaction apparently goes wonky in diabetics and the idea is that if you can kill PKCepsilon you can prevent the reaction which in turn prevents the damage.
There are many many metabolic steps between PKCepsilon and its phosphorylation and the production of excessive fat in diabetcs. Without knowing the hundreds (? thousands?) of intermediate reactions there's no reason to see any connection between this molecule and the end result of too much fat.
A drug that inhibits this enzyme would (hopefully) result in less fat being produced but it would be an extremely indirect result. By shutting off an early part of the metabolic pathway you could turn off the whole thing - assuming you don't screw up some other pathway that depends on this enzyme!
posted by Quietgal at 2:42 PM on October 5, 2007 [3 favorites]
PKCepsilon = Protein Kinase C epsilon.
So what's a protein kinase? It's an enzyme, which means that it is a protein that catalyzes a chemical reaction.
Kinases are enzymes that put a phosphate group onto something else (that's the chemical reaction).
"Protein kinase" means that the target is another protein, as opposed to some other type of molecule.
There are lots of different kinases, which is why they are given letters (A, B, C) so you know which one you're referring to.
Epsilon means that we've found subtle differences in a sample of what used to be thought of as a single unique enzyme (protein kinase C). If you purify protein kinase C from a piece of, say, liver tissue you will get a solution that contains thousands or millions of molecules. If you look very carefully in this population of molecules for these small differences you can see them. Presumably there are alpha, beta, gamma, and delta forms of protein kinase C as well as the epsilon form.
So let's come up for air and consider your macro-scale questions. PKCepsilon is definitely made by the body. It is present in fairly small amounts since it only has to catalyze a chemical reaction so it could not be considered nutritional (if I'm interpreting your question correctly - by "nutritional protein" I assume you mean the stuff that makes up the bulk of the proteins we eat, like the muscle proteins of red meat).
The generation of all proteins by the body consumes energy and raw materials (amino acids), so when your body makes the proteins it needs you could sorta consider it "anti-nutritional" since it's using up some of the energy and raw materials you get from the food you eat.
The article you linked to discusses the idea of knocking out this enzyme so it can't catalyze its chemical reaction (moving that phosphate group onto another protein). This reaction apparently goes wonky in diabetics and the idea is that if you can kill PKCepsilon you can prevent the reaction which in turn prevents the damage.
There are many many metabolic steps between PKCepsilon and its phosphorylation and the production of excessive fat in diabetcs. Without knowing the hundreds (? thousands?) of intermediate reactions there's no reason to see any connection between this molecule and the end result of too much fat.
A drug that inhibits this enzyme would (hopefully) result in less fat being produced but it would be an extremely indirect result. By shutting off an early part of the metabolic pathway you could turn off the whole thing - assuming you don't screw up some other pathway that depends on this enzyme!
posted by Quietgal at 2:42 PM on October 5, 2007 [3 favorites]
Yes, PKC is protein kinase c, and epsilon is a variant of this gene.
Kinases are enzymes, made by the body, as you said, that put phosphates onto other things, usually other proteins. This action is called "phosphorylation."
Phosphoyrlation of proteins either turns their function on or off, or makes them go places, or marks them for disposal -- speaking of phosphorylation in general is difficult, since it's the major "user interface" for proteins in general, and phosphorylation does different things to each protein on a case-by-case basis.
Protein kinase C is a large family of such enzymes, which can phosphorylate a wide variety of protein targets. Unfortunately, the linked article doesn't give a reference for the journal paper, so it's hard to anything more specific in this case (namely, what protein kinase C epsilon is phosphorylating, and why phosphorylation of that target protein turns off insulin secretion.)
posted by NucleophilicAttack at 2:43 PM on October 5, 2007
Kinases are enzymes, made by the body, as you said, that put phosphates onto other things, usually other proteins. This action is called "phosphorylation."
Phosphoyrlation of proteins either turns their function on or off, or makes them go places, or marks them for disposal -- speaking of phosphorylation in general is difficult, since it's the major "user interface" for proteins in general, and phosphorylation does different things to each protein on a case-by-case basis.
Protein kinase C is a large family of such enzymes, which can phosphorylate a wide variety of protein targets. Unfortunately, the linked article doesn't give a reference for the journal paper, so it's hard to anything more specific in this case (namely, what protein kinase C epsilon is phosphorylating, and why phosphorylation of that target protein turns off insulin secretion.)
posted by NucleophilicAttack at 2:43 PM on October 5, 2007
P.S. you can go to Pubmed and search for "biden pkc epsilon" to get some of these abstracts, although I'm not sure which one is the article in question.
posted by NucleophilicAttack at 2:45 PM on October 5, 2007
posted by NucleophilicAttack at 2:45 PM on October 5, 2007
I wrote a response to your question that was nowhere near as good as those seen on preview. One thing to add:
Here's the abstract for the study your linked article is referring to. My company apparently doesn't have a subscription for the electronic version of the journal, so I can't read the actual paper. Judging by the speed of the responses you've received so far, I'm sure someone who can will be along shortly.
posted by Thoughtcrime at 2:47 PM on October 5, 2007
Here's the abstract for the study your linked article is referring to. My company apparently doesn't have a subscription for the electronic version of the journal, so I can't read the actual paper. Judging by the speed of the responses you've received so far, I'm sure someone who can will be along shortly.
posted by Thoughtcrime at 2:47 PM on October 5, 2007
Here's what my quick glance through a med student's eyes says (People have already explained the basics very well, so I'll just add what I see from the paper itself)...
Previous work has shown that PKC epsilon is preferentially activated in mouse cells chronically exposed to fats. Now, mice exposed to high levels of fat develop a "metabolic syndrome" similar to the metabolic syndrome in humans, which, to simplify, includes type 2 diabetes. What the researchers at the Garvan Institute set out to do was produce mice *without* PKC epsilon and, uh, see what happened to 'em.
What appeared to happen was that, with normal diets, the new mice were no worse off than normal ones. With high-fat diets, however, the new mice did not develop the glucose intolerance that normal mice did. See, this intolerance is the basic mechanism behind the metabolic syndrome/type 2 diabetes: again, to simplify, if the body does not make enough insulin, it becomes intolerant to glucose, and all this bad crap happens. To quote the paper, "PKC epsilon might therefore inhibit insulin secretion under conditions of lipid oversupply." In other words, PKC epsilon may be Bad in the setting of high-fat diets.
What's more, when they took mice who model human type 2 diabetics, and blocked their PKC epsilon with a drug, their diabetes seemed to "improve"! i.e., their insulin response to a glucose load was better. Thus, the enthusiasm in the lay press about a possible new drug target in type 2 diabetes.
I have not evaluated the paper's methodology critically or anything, just reporting what they're claiming in the paper.
posted by sappidus at 2:52 PM on October 5, 2007
Previous work has shown that PKC epsilon is preferentially activated in mouse cells chronically exposed to fats. Now, mice exposed to high levels of fat develop a "metabolic syndrome" similar to the metabolic syndrome in humans, which, to simplify, includes type 2 diabetes. What the researchers at the Garvan Institute set out to do was produce mice *without* PKC epsilon and, uh, see what happened to 'em.
What appeared to happen was that, with normal diets, the new mice were no worse off than normal ones. With high-fat diets, however, the new mice did not develop the glucose intolerance that normal mice did. See, this intolerance is the basic mechanism behind the metabolic syndrome/type 2 diabetes: again, to simplify, if the body does not make enough insulin, it becomes intolerant to glucose, and all this bad crap happens. To quote the paper, "PKC epsilon might therefore inhibit insulin secretion under conditions of lipid oversupply." In other words, PKC epsilon may be Bad in the setting of high-fat diets.
What's more, when they took mice who model human type 2 diabetics, and blocked their PKC epsilon with a drug, their diabetes seemed to "improve"! i.e., their insulin response to a glucose load was better. Thus, the enthusiasm in the lay press about a possible new drug target in type 2 diabetes.
I have not evaluated the paper's methodology critically or anything, just reporting what they're claiming in the paper.
posted by sappidus at 2:52 PM on October 5, 2007
Protein kinase C has an epsilon isoform (ε), formed from an alternative splicing, or "edit" of the same transcription of the PKC genetic code. PKC is implicated in signal transduction.
Very roughly, signal transducers are switches that flip other switches on or off, making a "signal cascade" that results ultimately in something happening in the cell: for example, make less of this protein, start making more of this other protein, or start dividing; that sort of thing.
When PKC-epsilon is activated, the article suggests that this particular form of PKC is implicated in some signal pathway that decreases insulin levels.
Insulin itself flips switches that control how sugar gets used. Skimming over some other reading suggests that it affects signal pathways triggered by insulin itself, controlling the effect of insulin.
Since this protein controls both levels of insulin and (presumably) what effect insulin has, researchers can target their efforts on controlling PKC — thereby gaining more direct control over diabetes.
You can think of a cell roughly as a stubble-covered soccer ball. Some of the "stubble" are proteins that can carry signals into the cell.
Since PKC sits just underneath the surface of a cell, waiting for that stubble to get "stroked", it is something that drug researchers can more easily throw drugs at. It's easier to develop a drug when you don't have to worry as much about how to deliver into the cell.
If the drug surrounds the outside of the cell, and can affect the cell's behavior by latching on to a knobby, stubble protein on the cell surface that then flips PKC's switch, you're that much closer to an easy-to-administer cure.
posted by Blazecock Pileon at 2:52 PM on October 5, 2007
Very roughly, signal transducers are switches that flip other switches on or off, making a "signal cascade" that results ultimately in something happening in the cell: for example, make less of this protein, start making more of this other protein, or start dividing; that sort of thing.
When PKC-epsilon is activated, the article suggests that this particular form of PKC is implicated in some signal pathway that decreases insulin levels.
Insulin itself flips switches that control how sugar gets used. Skimming over some other reading suggests that it affects signal pathways triggered by insulin itself, controlling the effect of insulin.
Since this protein controls both levels of insulin and (presumably) what effect insulin has, researchers can target their efforts on controlling PKC — thereby gaining more direct control over diabetes.
You can think of a cell roughly as a stubble-covered soccer ball. Some of the "stubble" are proteins that can carry signals into the cell.
Since PKC sits just underneath the surface of a cell, waiting for that stubble to get "stroked", it is something that drug researchers can more easily throw drugs at. It's easier to develop a drug when you don't have to worry as much about how to deliver into the cell.
If the drug surrounds the outside of the cell, and can affect the cell's behavior by latching on to a knobby, stubble protein on the cell surface that then flips PKC's switch, you're that much closer to an easy-to-administer cure.
posted by Blazecock Pileon at 2:52 PM on October 5, 2007
(upon seeing my comment actually posted, I see that I have been a little too quick to write... really, the problem in type 2 diabetes is more of a *resistance* to insulin than insufficient secretion... but potentially, blocking PKC epsilon would allow mice/people to make enough insulin to overcome this resistance... all right, I'm going to let someone with more of a handle on this start talking now, heh...)
posted by sappidus at 2:55 PM on October 5, 2007
posted by sappidus at 2:55 PM on October 5, 2007
This thread is closed to new comments.
posted by rocketman at 2:25 PM on October 5, 2007