为什么人体保持37度体温

Why Does the Human Body Maintain a Constant 37-Degree Temperature?: Thermodynamic Switch Controls Chemical Equilibrium in Biological Systems Paul W. Chun (pwchun@biochem.med.ufl.edu) Professor of Biochemistry and Molecular Biology University of Florida College of Medicine Gainesville, Florida 32610-0245 INTRODUCTION Shortly after T.H. Benzinger published an article in 1971 in Nature entitled “Thermodynamics, Chemical Reactions and Molecular Biology,” the question arose whether thermochemical descriptions of biochemical systems that existed in the literature were inadequate or wrong or both. Benzinger did not formulate the problem in a way that would readily permit its general testing, and sufficient experimental data bases of adequate range and accuracy for such tests did not exist at that time. Thus, for some three decades, his conclusions were ignored. In discussions with Dr. Benzinger, I became intrigued by the question of how the basic laws of thermodynamics could and should be applied to the interacting biological systems I had studied for some 30 years. Lack of a fitting function for the Gibbs free energy change as a function of temperature has certainly hampered any understanding of thermodynamic behavior in biological systems ( Gibbs free [available] energy = Total heat − Bound unavailable energy). However, my subsequent studies have revealed many details of the thermodynamic and equilibrium properties of living systems. One of the most interesting discoveries and the subject of my presentation at the 48th Biophysical Society meeting in Baltimore, concerns the way in which the thermal set-point of a biological system is established and maintained on a molecular level. In the human body, that set-point is 37o Celsius or 98.6o Fahrenheit. Although it is has been recognized by generations of scientists that most warm-blooded animals maintain a constant body temperature, few bothered to ask why. I believe I have found the answer. Based on the analysis of available and highly precise data for a number of interacting protein systems, I have reached a number of overarching conclusions about their thermodynamic behavior. In all biological interactions, ∆Ho(T) and ∆So(T) are positive at low temperature. As reaction temperature increases, both ∆Ho(T) and ∆So(T) become negative, creating a negative minimum of Gibbs free energy change at . Here the balance of ∆Ho(TS)(−) = ∆Go(TS)(−)minimum and T∆So(T) = 0 at , as seen in the accompanying figures. The change of sign in ∆Cpo(T)reaction leads to true negative minimum in the Gibbs free energy of reaction, that is ∆Cpo(T)(+) → ∆Cpo(T)(−), designated as a thermodynamic molecular switch. It is known that living systems can survive and operate optimally only at a sharply defined temperature, or over a limited temperature range where the balance of energy and entropy demands is favorable at best. The implication is that basic macromolecular interactions exhibit a well-defined negative free energy minimum as a function of temperature. Such a situation is not common in simple chemical systems where a monotonic change of ∆Go, ∆Ho, and Keq over an experimental temperature range is typical. In a succession of publications, I have defined a thermodynamic molecular switch for various biological systems. At a well-defined stable temperature − 37o C. in the human body − there will be a negative minimum of free energy change and the maximum work can be accomplished for such essential life processes as transpiration, digestion, reproduction or locomotion. It is my contention that the thermodynamic molecular switch is a universal feature of living systems, one in which a change in sign of the specific heat capacity change (the capacity to hold heat) of reaction leads to a negative minimum in the Gibbs free energy change of reaction and a maximum in the related equilibrium constant. In assessing my thermodynamic work, Robert J. Hanrahan, professor of chemistry at the University of Florida, said, “ Professor Chun has provided a detailed and elegant description of how the body’s thermostat works, published in more than 20 papers in significant scientific journals. But because of the fragmentation of modern science, few chemists are aware of this work − although the arguments are based on straightforward (if detailed) thermodynamics.” I have applied the Planck-Benzinger methodology I have developed to protein folding; protein- protein, protein-nucleic acid or protein-membrane interactions, and protein self-assembly, and have found that all these interacting biological systems exhibit a thermodynamic molecular switch at a molecular level. It seems apparent that the existence of a thermodynamic molecular switch may be universal in living systems. Researchers who fail to consider it in their analysis of energy differences in biological systems risk a conclusion that is inadequate, inaccurate − or both. THERMODYNAMIC MOLECULAR SWTICH Applying the Planck-Benzinger methodology to numerous biological systems, I have established that the negative Gibbs free energy minimum at a well-defined stable temperature, , where the bound unavailable energy T∆So = 0, has its origin in the sequence-specific hydrophobic interactions. Each such system examined confirms the existence of a thermodynamic molecular switch wherein a change of sign in [∆Cpo]reaction leads to a true negative minimum in the Gibbs free energy change of reaction, and hence a maximum in the related equilibrium constant, Keq. At this temperature, , where ∆Ho(TS)(−) = ∆Go(TS)(−)min, the maximum work can be accomplished in transpiration, digestion, reproduction or locomotion. In the human body, this temperature is 37 oC. The values may vary from one living organism to another, but the fact that the value of T∆So(T) = 0 will not. There is a lower cutoff point, , where enthalpy is unfavorable but entropy is favorable, i.e. ∆Ho(Th)(+) = T∆So(Th)(+), and an upper limit, , above which enthalpy is favorable but entropy is unfavorable, i.e. ∆Ho(Tm)(−) = T∆So(Tm)(−). Only between these two temperature limits, where ∆Go(T) = 0, is the net chemical driving force favorable for such biological processes as protein folding, protein-protein, protein-nucleic acid or protein-membrane interactions, and protein self-assembly. All interacting biological systems examined using the Planck-Benzinger methodology have shown such a thermodynamic switch at the molecular level, suggesting that its existence may be universal. CONCLUSION Application of the Planck-Benzinger methodology to biological systems has demonstrated a basic rule for life processes, in that there is a lower cutoff point, , where entropy is favorable but enthalpy is unfavorable, i.e. ∆Ho(Th)(+) = T∆So(Th)(+), and an upper cutoff, , above which enthalpy is favorable but entropy unfavorable, i.e. ∆Ho(Tm)(−) = T∆So(Tm)(−). Only between these two limits, where ∆Go(T) = 0, is the net chemical driving force favorable for such biological processes as protein folding; protein-protein, protein-nucleic acid, or protein-membrane interactions; and protein self- assembly. The significance of a negative Gibbs free energy minimum in the equilibrium of biological systems is simply that one is dealing with a true condition of stability, that is, maximum Keq of reaction. The value may vary from one organism to another, but the fact that the value of T∆So(T) = 0 will not. ------------------------------------------------------------------------------------------------------------------------------- As experimentally observed in interacting biological systems such as α-chymotrypsin dimerization at low temperature, ∆Ho and ∆So are both positive, becoming negative as temperature increases, whereas ∆Go changes from positive to negative, then reaches a negative value of maximum magnitude at , and finally becomes positive as temperature increases (figure on the left ). That is, process 1 goes to process 2, creating cooperative enthalpy-entropy compensation between and , where both ∆Ho(T)(+) and T∆So(T)(+) intercept at . Both ∆Ho(T)(−) and T∆So(T)( −) intercept at . This process is illustrated schematically at right. ------------------------------------------------------------------------------------------------------------------------------------- The Planck-Benzinger methodology provides a means of determining the innate temperature- invariant enthalpy, ),T(H 0 o∆ thermal agitation energy, or the heat capacity integrals, ,dT)T(CpT 0 o∫ ∆ and allows precise determination of , , and . It is the best method for evaluating ],T(HH[ 0 oo 298 ∆−∆ the heat of reaction for biological molecules at room temperature, and provides for a better understanding of cooperative thermodynamic compensation. It can be effectively applied to the thermodynamic analysis of site-directed mutagenesis. It is apparent that the critical factor driving interacting biological systems is a temperature- dependent heat capacity change of reaction, ∆Cpo(T)reaction, which is positive at low temperature but switches to a negative value at a temperature well below the ambient range. This change of sign of the critically important ∆Cpo(T)reaction has such significant consequences that it is referred to as a thermodynamic switch. It determines the behavior patterns of the Gibbs free energy change, and hence a change in the equilibrium constant, and /or spontaneity. All interacting biological systems we have thus far examined using with the Planck-Benzinger approach point to the universality of this thermodynamic switch [1-10]. References 1. Chun, P. W., (2000a) Biophysical J. 78, 416. 2. Chun, P. W., (2000b) Cell Biochemistry and Biophysics, 33, 149. 3. Chun, P. W., (2000c) Int’l. J. Quantum Chem. 80, 1181. 4. Chun, P. W., (2001a) J. Colloids a and Interfacial Science, 181,183. 5. Chun, P. W., (2001b) Int’l. J. Quantum Chem. 85, 697. 6. Chun. P. W., (2002) Int’l. J. Quantum Chem. 87, 323. 7. Chun, P. W., (2003a) Biophysical Journal 84, 1352. 8. Chun, P. W., (2003b) The ScientificWorldJournal 3, 176. . 9. Chun, P. W., (2004a) Accepted in Physica Scripta. 10. Chun, P. W., (2004b) Accepted in J. Applied Physics.