Biological oxidations and energy conservation

Biological. Oxidations. andEnergy Conservation. All organisms require energy for growth and maintenance. Some organisms derive their en- ergy from the...
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Joel Kirschbaum Squibb Institute for Medical Research New Brunswick, N e w Jersey 08903

Biological Oxidations and Energy Conservation

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organisms require energy for growth and maintenance. Some organisms der~vetheir energy from the sun, trapping its radiation through the process of photosynthesis ( 1 ) . Organisms that cannot perform photosynthesis are dependent for their energy and maintenance on the sugars, fats, and proteins produced by organisms that possess photosynthetic pathways. Thesc sugars, fats, and proteins have stored as t,heir chemical bonds much of the energy that was required for their synthesis. The stepwise oxidation of these foodstutfs by living organisms releases their encrgy for various cellular processes. The amount of energy available from the oxidation of a molecule such as glucose may be calculated by considering the non-biological combustion of the molecule, for example glucose oxidation,

+ GO1

CBHllOa

-

GC02

+ GH20

yields 686,000 cal. If released instantaneously as heat, its cnergy could neither be stored for use a t a later time nor used in small quantities. However, a series of biological catalysts, i.e., enzymes, permits the stepwiee rclease of the 686,000 cal a t lower temperatures. The energy released in this sequential oxidation is used to synthesize energy storing and releasing compounds such as adenosine triphosphate, or ATP, (Fig. 1) from

bonds, which contain not the usual ester bond energy of 1,000-3,000 cal/mole hut 9,000 cal/mole ( 2 ) as measured by the heat of hydrolysis. If the energj--releasing hydrolysis of ATP could be coupled with a reaction requiring external energy to proceed essentially to completion, then the endothermic reaction could be accomplished, just as a car may coast up a small hill after first rolling down a large hill. More specifically, AGO is related to the equilibrium constant by the expression AGO = -RT in I< (where R = gas constant, T = temperature, and K = equilibrium constant). If AGO is negative, product predominates. If AGO = 0, then K = 1 and the ratio of product(s) to reactant($ is 1; and, if AG" is positive, little product may be formed, unless energy is supplied to the system to drive the reaction in the direction of product formation. One example of such an ATPdriven reaction is ester synthesis, which may be expressed as follows, where AMP denotes adenosine monophosphate: ATP

+ RCOIH s RCO,AMP + pyrophosphate AGO = 0 eal

RCO.-AhlP

(1)

+ ITOR'S RCOzRt + adenosine monophosphate AGO = -2000 C ~ I (2)

There are several reasons why the hydrolysis of pyrophosphate bonds, such as in ATP, releases approximately 9,000 cal/mole, while the hydrolysis of monophosphates, such as a-glycerophosphate, HCOH,

I

HCOH

Figure 1. Adenosine triphorphote (ATPI. The hydrolysis of either phorphote group marked with on asterisk releorer approximately 9000 c o i l mole.

releases only 1,000-3,000 cal/mole. First, the products of the hydrolysis of ATP (inorganic phosphate and adenosine mono- or diphosphate) have many more resonance possibilities than the parent ATP; inorganic phosphate has one more oxygen free for electron resonance than when the phosphate is a part of an ATP molecule (3).

adenosine diphosphate and inorganic phosphate. The dependence of living organisms on adenosine triphosphate (ATP) or related compounds, e.g., creatine phosphate, to provide energy for motion, for protein synthesis, for nerve conduction, and even for thinking, is absolute, and complex mechanisms exist in nonparasitic nonphotosynthetic creatures for the oxidation of foodstuft's. (Photosynthetic catalysts lead not only to the incorporation of COa into organic molecules by reduction but also to ATP formation.) The most important property of ATP is the high energy content of it,s pyrophosphate (phosphate diester)

Second, P=O, which may also be represented by P+0- in a phosphate diester bond, indicates that there is considerable unrelieved repulsion between charged oxygen atoms and phosphorus atoms. Third, steric crowding between oxygens on adjacent phosphate groups is relieved by hydrolysis, and the subsequent separation of bulky groups also releases energy originally required for bond bending.

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lournol of Chemical Education

shown in Figure 2. Two steps in glycolysis lead to ATP synthesis via whstratelevel phosphorylation. The first step is the oxidation of glyceraldehyde-3phosphate to 1,3-biphosphoglyceric acid. This is accomplished by means of the enzyme glyceraldehyde-3phosphate: nicotinamide adenine dinucleotide reductase (6). For the oxidation of glyceraldehyde - 3 - phosphate, the electron acceptor is the low molecular weight comy to two molecules of pywvic acid, Figure 2. Glyc~lysis. GIYCOIB. with l i x carbon atoms, i, ~ x i d o t i v ~ lcleaved pound nicotinamide adenine a three carbon atom-containing molecule. dinucleotide, abbreviated NAD or NAD+ (Fig. 3). The reduction of NAD is stereospecific when the pyridinium (nicotinamide) ring Most ATP is synthesized by the energy released in a adds a hydrogen and an electron to form a 1,4dihydromulti-step combination of oxygen with hydrogen from pyridine derivative. The hydrogen may add to either such substrates (or enzyme reactants) as fats and sugars side of the pyridinium ring, (A) or (B), depending on (e.g., glucose). After examining briefly the oxidation which of the many XADcoupled enzymes is reacting of food stuffs to yield hydrogen, the oxidation of hydrowith a particular substrate. NADH may then disgen to give the energy required for ATP synthesis sociate from the enzyme. followed by investigations in ATP synthesis will be The oxidation of glyceraldehyde-3-phosphate to 1,3discussed. hiphosphoglyceric acid initially involves the reaction of Sources of Hydrogen for ATP Synthesis the aldehyde with a sulfhydryl group associated with Partial Oxidofion of Glucose via Glycolysis the enzyme glyceraldehyde-3-phosphate dehydrogenase followed by the formation of an acyl enzyme intermediThe major mammalian oxidative pathway of glucose, ate (7). and some other carbohydrates, can be divided into two 0 0 major divisions. Paradoxically the first portion may 1I II occur without oxygen and is called glycolysis (Fig. 2) R-C-H + HS-Enz-NAD R-C-S-Ena-NADII (3)

(4).

To initiate glycolysis, one molecule of ATP is required to phosphorylate each molecule of glucose, converting the neutral monosaccharide into a charged molecule (5) which is then capable of faster and tighter binding to a reactive enzyme. The phosphorylated glucose then readily undergoes a series of reactions to 3-carbon fragments and ATP as

0

0

HzCOPO:' -

The high AGO of hydrolysis of the newly formed phosphate group of 1,3-biphosphoglyceric acid, which is approximately -13,000 cal at pH 7, leads to the facile phosphorylation of ADP to yield ATP. The equilibrium constant for this reaction is approximately 3 X

lo3.

Figure 3. The structure and mode d reduction of ntotinomide adenine Nicotinomide adenine dinucleotide phordinucleotide (NAD or NAD% phote INADP) contoins o third phosphate ester ot the hydroxyl group marked with on arterirk

A second molecule of ATP is synthesized by the transfer of a phosphate group from phosphoenol pyruvate to ADP. The formation of the stable molecule pyruvate from the en01 form energizes this reaction. In some other species than mammals and in some mammalian tissues, alternative pathways from glucose to pyruvate predominate. These pathways usually involve the oxidation of glucose-6-phosphate by NADP from an aldehyde to an acid and the oxidation of a hydroxy group to an 0x0 (keto) group (8). Glyceraldehyde-3-phosphate tends eventually to be a product of these reactions and is usually oxidized to pyruvic acid, as indicated in the glycolytic scheme. Pyruvic acid, formed in the last step of glycolysis, is the starting compound for a series of oxidative reactions found in organisms from protozoa to mammals resulting in the formation of NADH, COz, and ATP. If oxygen is lacking, pyruvic acid may be reduced to lactic acid utilizing NADH as the reducing agent. The conservaVolume 45, Number 7, January 1968

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H-C-H

MERc.pTo-

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L&,",NE

NH2

H-C-H

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N"C\C'N\\o I

NH

- - - -1. .. .......... C=O

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A~SWOS~NC 3.P"O%~"ATE

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