Müller I. A history of thermodynamics. The doctrine of energy and entropy (Müller I. A history of thermodynamics. The doctrine of energy and entropy.pdf), страница 71

Having said this, I hasten to add that in the sequel, although weshall always be dealing with enzyme-catalysed reactions, we shall largelyignore the enzymes; and we are able to do that, since presumably – or bydefinition – the catalysers do not contribute to the energies and entropies ofthe reactants and resultants.The most evident difference between the burning in an open fire andburning inside animal bodies is that the latter occurs slowly and at bodytemperature. In fact, it is common knowledge that human life is severelyjeopardized when a person has a temperature beyond 42°C. The reason forthis high sensitivity of organic material against heat was discovered byLinus Carl Pauling (1901–1994), who suggested in 1936 that the properfunctioning of proteins (say) depended to a large extent on weak hydrogenbonds.

Such bonds provide a precarious stability to organic macromoleculeswhen they are folded in a particular fashion. Pauling even envisaged helicalprotein molecules and thus became a forerunner of the biochemistry of thegenetic code.9As we eat them, starch, lipids and proteins have no chance to arrivewhere we need their structural units, the glucose, fatty acids and aminoacids: We do not need them in the digestive tract but rather inside the bodytissue, – in the blood, the liver, etc. The large molecules of food must bebroken down before they can be absorbed by the tissue, and that break9The notion of molecular helicity helped Francis Harry Compton Crick (1916–2004) andJames Dewey Watson (1928– ) to uncover the shape of nucleic acids (DNA).31411 Metabolismdown happens during the digestive catabolism.

Catabolism is the Greekword for break-down. Let us take starch as an example, which is essentiallya long chain of glucose molecules.Of course, it is common knowledge that the stomach contains acid juices,and they might go a long way to break up the starch into glucose. The studyof gastric digestion begins in the Wild West in the year 1819 where WilliamBeaumont (1785–1853) was surgeon of a border post in northern Michigan.One of his patients had received a bullet wound that left him with a fistula –an opening – leading to the stomach.

Thus Beaumont was able to study thechanges which the food undergoes in the stomach, and he did so with somuch enthusiasm that the patient eventually ran away from him. That was awise decision on the part of the patient, because away from his doctor helived to the old age of 82 years,10 always with the fistula.Later, and in a different part of the world, the physiologist ClaudeBernard (1813–1878) created fistulae artificially in different parts of thedigestive tract of animals. He was heavily attacked for this by the antivivisectionists of the day, including his own wife, who left him over theissue. However, Bernard was able to discover that digestion does notexclusively happen in the stomach.

By inserting foodstuffs into the smallintestine he showed that the major part of the digestion takes place there,under the influence of the secretions of the pancreas, the large glandsituated below the stomach.As time went on, the enzymes were discovered and their nature asproteins with very specific capacities to catalyse reactions.

Digestiveenzyme activity begins actually in the mouth, where the saliva contains theenzyme amylase which breaks up starch, – or helps water to break up theglycoside links between the glucose molecules that form starch. This is whybread, if kept in the mouth long enough, develops a distinctive sweet taste.Further down the digestive track other enzymes pitch in, so that, when thesmall intestine is left, the food is largely split into its structural units: Notonly starch into glucose, but also lipids into fatty acids, and proteins intoamino acids. Whatever is not broken up at that point is excreted.Chemically speaking the break-up occurs through enzyme-assistedhydrolysis, the insertion of water molecules between the structural units ofthe macromolecules, or the reverse of condensation. Hydrolysis breaks upthe glycoside- and ester- and peptide-bonds in the food.

These areexothermic processes, although the heats of reaction are small.That is the first step of catabolism, the food break-down. Now, the smallbreak-down products, viz. glucose, fatty acids and amino acids are able topass the intestinal membranes out of the digestive tract and into the bodytissue itself, where they are decomposed further; remember that we mustend up with CO2 and H2O – and urea.10I. Asimov: ‘‘Biographies...” loc.cit. p.

268.Tissue Respiration315Tissue RespirationThe discovery of the modes of break-down of glucose inside the body tissueoccurred in the first half of the 20th century. To a non-chemist like myself itrepresents the successful assembling of the most amazing inventive puzzle,based on the flimsiest evidence.

In the beginning it was known that glucose(say) enters the tissue through the intestinal walls and that oxygen enters theblood through the lungs and is carried to the body cells by hemoglobin, thestuff that gives blood its red colour. But how do those two componentscome together in order to react and liberate the energy and consume entropyaccording to the stoichiometric equation, see aboveC6 H12O6 6O2  6CO2 6 H 2OkJ∆hR 2798 molJ∆sR 241 molKsuch that the Gibbs free energy – which is the essential quantity – decreaseskJby 2873 mol, if the reaction occurs at the body temperature of 37°C.Actually it turns out that the glucose molecule is first decomposed intotwo lactic acid molecules C3H6O3 before the interesting things happen.Therefore we rephrase the above question and ask how lactic acid reacts withoxygen to form CO2 and H2O.The problem was approached from opposite ends: The consumption ofoxygen and the lactic acid oxidation.

Both occur separately so that lacticacid and oxygen never get together directly chemically. The earlychampions of the discovery were the chemists Heinrich Otto Wieland(1877–1957) and Otto Heinrich Warburg (1883–1970) and both engaged ina fruitful scientific controversy.Warburg had invented a manometer that could be used to measure theuptake of oxygen by tissue and he observed that the oxygen combined withheme enzymes. He did not know what the oxygen was doing there, but hisinsight and experimental acumen were rewarded with the 1931 Nobel prize.Wieland on the other hand recognized that the oxidation of lactic acidproceeds by dehydrogenation, i.e.

the splitting-off of two hydrogen atomsfrom the organic molecule. Subsequently the two bonds left free in lacticacid – by the departure of the hydrogen atoms – join to form a double bondC = O inside the molecule – a keto group – which, with water, is convertedto a CO2 molecule plus another pair of hydrogen atoms. There remainsacetic acid CH3COOH as the organic compound to be broken down further.After Wieland, one of Warburg’s students, Hans Adolf Krebs (1900–1981) – Sir Hans Adolf after 1958 – took up the matter of dehydrogenationand invented the Krebs cycle which can attach an acetic acid molecule to anenzyme and grind it down to individual H-atoms and CO2 and then returnand be ready to accept the next acetic acid molecule for grinding down, etc.The overall formula – starting from lactic acid – reads31611 MetabolismC3 H 6O3 3H 2O  3CO2 12 H .The six pairs of hydrogen atoms are handed down a sequence of enzymeswith which they build tighter and tighter bonds, before they reach oxygenand form water.

The energetic downward steps are such that each hydrogenpair activates three adenosine tri-phosphate molecules. These so-calledATP’s are the molecular energy carriers and we shall describe them anddiscuss their action in a short while.Fig.11.2. Wieland, Warburg and Krebs, pioneers of intermediary metabolismBefore that, however, let it be said that the Krebs cycle is not onlyinvolved in glycolysis, the breaking up of sugar, but also in the catabolismof fatty acids and of amino acids.

Fatty acids and amino acids are firstbroken down to acetic acid which can then enter the Krebs cycle just as theacetic acid originating from lactic acid does. The catabolism of fatty acids isparticularly productive of new ATP’s, which we shall now proceed todiscuss.AnabolismObviously the energy – or enthalpy – of reactions in the tissue does not allappear as heat, as it does in a flame. Indeed, an animal and man are able toexert power, and they must do so, at least to the extent of the basalmetabolic rate. Also animals grow, and they are able – in their bodies – toproduce fat even if they ingest primarily carbohydrates.

So they are buildingup complex molecules from the simpler ones that have entered their tissue.The process is called anabolism from Greek: to build up.A first case of anabolism was discovered as early as 1856 by Bernard, thevivisectionist. He noticed that glucose is converted into glycogen, a starchlike substance in the liver. And he also saw that glycogen regulates thesugar content of the blood: If the blood is swamped with glucose, glycogenis formed , and if there is too little glucose in the blood, glycogen falls backAnabolism317to sugar. Diabetes happens, if that balance fails to function. Therefore,obviously, the liver is capable of forming starch from glucose, just theopposite of what the digestive track achieves.Two things are interesting about the balancing act between glucose andglycogen: Firstly, that it proceeds through sugar phosphate, albeit only as anintermediate,11 and secondly that adenosine tri-phosphate is involved, anorganic compound – invariably abbreviated as ATP – which was discoveredin 1929 by the biochemist K.

Lohmann. He found that phosphoric acidH3PO4, which had been thought to belong firmly to inorganic chemistry,played an important role in muscle action.ATP results from phosphoric acid by condensation of three phosphoracid molecules and an adenosine molecule which we may write as R–OH,since its exact form does not concern us. Thus ATP has the structuralformulaThe biochemist Fritz Albert Lipman (1899–1986) noticed that the twophosphate ester bonds marked by an arrow can be more easily hydrolizedthan the bond near the adenosine, and his interpretation was that those twobonds lie at a higher level of free energy. Quantitatively it seems that therekJis about 30 molto be gained from a reaction involving a high energy bond,twice as much as from the low energy one.Now, back to the glucose–glycogen balance.

This will help us tounderstand what ATP does with its high energy bonds. If we characterize aglucose molecule by 1* ¢ ² 1* , the glycogen molecule may bewritten in the formOH ÃÓOÃÓOÃÓ O " ÃÓ OHand one might assume that this chain results from a direct multiplecondensation of glucose. However, this is not so. Indeed, in the 1930’s CarlFerdinand Cori (1896–1984) and his wife Gerty Theresa Radnitz Cori(1896–1957) found that the formation of glycogen proceeds in two steps asfollows.11The metabolic reactions inside the body tissue are called intermediary metabolism.,because it is the intermediates that play the most decisive role.31811 MetabolismStep (I): Formation of glucose phosphate and ADP from glucose andATPStep (II): Shedding of phosphorous acid:The energy-consuming step is the first one and the energy needed for theformation of glucose phosphate results from the de-activation of one of thehigh energy bonds of ATP which sinks down energetically to become ADP,i.e.

adenosine di-phosphate with only one high energy bond.Thinking mechanically we may say that the high energy bonds are likecompressed springs. In that visualization, step (I) of the above reactionreleases the spring and allows the subsequent uncoiling to lift the emergingcompound glucose phosphate to its high level of energy. Actually, afterLipman’s discovery, ATP has been found in body chemistry at all pointswhere energy is needed. One may say that the large amount of energycontained in food is broken down – by tissue respiration as explainedabove – into energetic small change appropriate to pay for molecularreactions in the course of anabolism. Thus reactions with ATP allow acompound to move uphill energetically.On Thermodynamics of Metabolism319On Thermodynamics of MetabolismOne often hears it said that the functions of life create order and shouldtherefore decrease entropy, cf.