Re: Can pyruvate replace glucose in the process of respiration?

Hello,
I am not entirely sure I understand your question (or at least the last 
staement about yeast and water is throwing me off). So, if I don't answer 
it well enough, please resubmit it or email me.

Yes, the body can and does use fuel molecules other than glucose to burn 
in its cells. You mention a few common examples, including the ability of 
the body to burn fructose (which is done by phosphorylating it to convert 
it to fructose 6-phosphate and feeding into the glycolysis pathway) and to 
burn fats (which are picked up by most cells after the liver has converted 
it into a form that the cells can convert into Acetyl-CoA and feed into 
the citric acid cycle).

By analogy, it might be useful to think of glucose as money. Sure, if you 
are a doctor and I am a farmer, and go to see you when I am sick, it might 
be just find in some cases if I pay you with three chickens; but, overall, 
the system is more versatile and easier to manage if most of the time you 
are paid in money rather than chickens. This is not to say that the 
chickens have no value; but, they are harder for you the doctor to get at 
that value, especially if the doctor has no chicken coop and is not going 
to kill them and eat them right away. Sure, a cell might be able to get 
its fuel from pyruvate in principle; but, using many different sources 
like that has its logistical problems.

Let me explain:

There are two main issues operating here and it is helpful to understand 
them: 1) cells use their cell membranes to control what can come into and 
leave a cell. Many substances such as pyruvate do not enter and leave the 
cell easily. Also, pyruvate (unlike glucose) is not a major part of the 
fuel in our diets and it would require more conplicated conversions of our 
foods to make pyruvate a central part of our fuel distribution system (the 
bloodstream). Glucose is able to enter the cell because of specific 
proteins in their cell membranes that permit glucose to enter the cell. 

More important is issue 2: the body finely controls many aspects of 
respiration and it is easier to do so if there is one main form of fuel. 
Each fuel has technical difficulties when the body transports them in 
quantity. If the sugar concentration in the blood gets too high, the blood 
will become more viscous. This will make it harder to pump, making the 
circulation to extremities very poor and may even make the person prone to 
blood clots and the like. This can be very dangerous, so the body secretes 
insulin when the sugar concentration in the blood gets high, and this 
induces some tissues (primarily muscles and the liver) to take glucose 
from the blood and store it for future use. When this system breaks down 
(i.e. diabetes), many problems ensue. Loss of sensation in hands and feet 
doe to the poor circulation is common and can be a serious problem. 
Sometimes untreated diabetics can burn their hands without any sensation, 
and the recoil reflexes thus do not work. (If you touch a hot stove by 
accident, you will jerk your hand away quickly and thus limit the burn 
damage.) In wintertime, sometimes the circulation is so poor that tissue 
dies and becomes infected. It is not terribly uncommon for poorly treated 
diabetics to need toes amputated for this reason.

So, just by this one example, you can understand that managing the fuel 
levels in the blood is very important. Pyruvate, if it were used would 
come with its own set of problems including the danger of changing the pH 
of the blood if large quantities are put into circulation to fuel (for 
example) someoen running a long distance. The body has chosen glucose as 
the main currency of its fuel and thus has developed systems such as 
insulin and insulin responsiveness to manage fuel supplies properly. Also, 
the storage of glucose in the muscles and liver as glycogen is also part 
of this management scheme.

Perhaps the body might have chosen something other than glucose and given 
the right management scheme, metabolism would work just as well as it does 
now with glucose. But, that's not the way it worked out.

In fact, the reason it worked out to be glucose is probably because we 
inherited our respiration pathways from yeast and bacteria. And many of 
these yeast and bacteria needed to ba able to grow whether or not oxygen 
was present. You can get energy out of glucose without oxygen by going 
through the glycolysis pathway; but, you can't do that for pyruvate. 

(There are bacteria (and perhaps also yeast, I don't know) that use 
alternative sources of energy, including the oxidation of sulfur from 
naturally occurring iron sulfides; but, I doubt we could use these 
pathways ourselves.)


I hope this helps.

Jeff Dorfman
National Institutes of Health
jdorfman@nih.gov