MadSci Network: Biochemistry

Re: At what temperature are the human body's enzymes rendered ineffective?

Date: Mon Mar 8 14:36:06 1999
Posted By: Michael Maguire, Faculty,Case Western Reserve Univ.
Area of science: Biochemistry
ID: 920744823.Bc

The answer is a very general one for two reasons.  The answer is 
undoubtedly complex plus we have little actual data in whole organisms (as 
opposed to your experiment measuring a single isolated enzyme). 

First, consider increased temperature.  At the body temperatures 
compatible with life (up to about 106-8 deg F), there are actually 
relatively few enzymes that will actually die.  However, all are probably 
affected, some more than others.  In addition, structural proteins will be 
changed slightly.  Most important, in my opinion, at higher temperatures 
would be the membrane and its lipid components.  Humans are optimized, for 
the most part, to function optimally at 98.6 deg F.  If you heat our 
membranes to a higher temperature, they get progressively leakier. Since 
the ionic balance (homeostasis) across membranes is absolutely crucial for 
health and life, this leakage poses a major problem.  Much of the 
leakiness is not from proteins, but from the lipid of the membrane.  
Basically, think of what happens if you take a cold stick of butter 
(lipid) out of the refrigerator and leave it out on the counter to warm to 
room temperature.  It doesn't actually melt to a liquid, but it become 
very soft, cannot hold its shape well.  Then think what this would 
translate to if the butter/lipid were only two molecules thick, as a 
membrane is.  That softness would not help the cell function nor help it 
hold its shape.

I doubt that at 106 deg F as in a fever many proteins become inactive.  
But organisms are very finely balanced machines.  If there are 10,000 
parts in a cell and 1000 of them change in activity all of a sudden by 5-
10%, and say 10 of those parts form an important linked sequence of 
reactions (a pathway), then the throughput for that pathway would be 
changed by (1.1)e+10 or about 250%.  Think of this happening in several 
pathways.  In addition, many proteins are unstable to temperature in this 
range, though not many.  So, in some pathways, one of the linking enzymes 
does die, or decreases in activity so much, that the pathway becomes 
effectively blocked.  The combination of this happening in several 
pathways at once could clearly be deleterious to the organism.

Second, consider decreased temperature.  This is easier.  Basically, there 
are few proteins that die at cold temperatures, but live at higher 
temperatures.  You can cool an organism down quite a lot before it dies, 
IF, repeat IF, the cooling and then subsequent warming are gradual.  Even 
whole organisms (but only simple ones) can be frozen and revive when 
thawed.  As an example, think of how your hands feel in the winter 
sometimes after being outside, even perhaps with gloves on.  Your hands 
are cold and stiff, but they still function.  The actual temperature of 
your fingers can and repeatedly often does get down to 40-50 deg F without 
any lasting harm at all.  What has to stay warm is your core body 
temperature and your brain.  The reason is your nervous system.  At lower 
temperatures, nerves do not function as well, and your metabolism provides 
less energy (ATP) to run things.  This further messes up the nerves 
because they need energy to maintain the crucial ion balances across the 
membrane so that nerve (electrical) impulses can be transmitted.  If the 
cooling goes on too long, they cannot readily recover.  This means that 
the nerves controlling the brain, and especially the heart and kidneys 
quit operating, thus risking heart stoppage.  When that happens, the 
organism is highly unlikely to recover since the heart is unlikely to 
start spontaneoulsy when warmed, though it can.

In terms of enzymes individually, yes, all of OUR enzymes will eventually 
die when heated too much.  Some in the range of 110 deg F, some not until 
much higher, perhaps even 160-170 deg F.  But there are organisms, some of 
them rather complex, that can grow at very high temperatures and/or very 
high pressures, such as the small animals, tube worms and a plethora of 
Bacteria and Archaea in deep sea vents, where the pressure is 300 
atomspheres and the release of gas and even magma can heat the water to 
boiling.  We use enzymes from such organisms in the laboratory precisely 
because they can survice very high temperatures.  In my laboratory, I have 
a membrane ion transporter that I have cloned both from a mesophile, 
Salmonella typhimurium (mesophile = moderate temperature, meaning our 
temperature) and an extremophile Methanococcus jannaschii (extreme hot or 
cold or pressure, in this case both high temperature and high pressure).  
They are the same basic protein, transporting the same ion, and have 
considerable sequence identity.  However, the protein from S. typh. starts 
to die at 50 deg Centigrade and is completely dead by 65 deg C, whereas 
the protein from M. jann. is still fully active at 70 deg C, the highest 
temperature we could go to.

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