Erik

Daniel Majcher
IPHY 3700: Marie Boyko

Submitted 11-23-2010
Origin of Life: The Enzyme World
Most theories and research regarding the origin of life have been primarily
concerned with the origins of DNA and RNA. These theories argue that either DNA or
RNA formed first and once formed, they led to the production of enzymes. An example
of such a theory is The RNA World Hypothesis, a leading abiogenic theory, which argues
that RNA formed prior to DNA, enzymes and proteins. It is certainly true that DNA and
RNA are necessary to sustain our current evolutionary state of life, however, the RNA
world hypothesis and other abiogenic theories that are primarily concerned with RNA fail
to provide a sufficiently logical explanation as to how or why RNA would have formed
in the first place. In this article an alternative abiogenic theory will be presented, which
will make the argument that based on their inherent characteristics enzymes were the first
to arise in the origin of life and are responsible for the development of RNA as well as all
organisms and their associated characteristics.
The RNA world hypothesis is similar to the present enzymatic world hypothesis,
in the sense that it was developed based on the discovery of ribozomes, which are RNA
molecules capable of catalyzing reactions - just as enzymes do. The primary distinction
between the two theories being that ribozomes are only capable of catalyzing reactions
that result in the coupling of elements, instead of and their building-blocks, nucleotides,
have been relatively difficult to produce in laboratory settings compared to enzymes.
Conversely, enzymes catalyze thousands of reactions and their building blocks, amino
acids, were successfully produced in the Miller-Urey experiments over 50 years ago.
Enzymes posess several characterstics, which support the idea that they emerged
first in the origin of life. The primary enzymatic trait being that they lower the activation

Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
energy of chemical reactions, which is the energy that needs to be put into a chemical
reaction in order for it to proceed. By lowering the activation energy or the amount of
energy necessary for a reaction to occur, enzymes would have provided the path of least
resistance for elements in pre-biotic earth to reduce their stored potential energy.
Additionally, since enzymes are not consumed in the reactions they catalyze and catalyze
a wide variety of reactions that yield various products, the products of catalyzed reactions
could potentially become associated with and provide enzymes with an evolutionary
advantage over other entities for survival, i.e., less susceptible to the degradive effects
of earths environment. Enzymes are also highly involved in the transcription and
translation of DNA and RNA, so it is at least plausible that DNA and RNA could have
been formed from enzymes; however, based on the previously-mentioned enzymatic
traits it seems more likely that enzymes formed first in the origin of life, instead of DNA
and RNA.
External energy, or more specifically, solar energy has been entering earths
environment for billions of years now, primarily via electromagnetic waves from the sun.
Due to this prolonged exposure to an external energy source, elements on the earth have
consequentially been raised from lower energy states to higher energy states. The
elements that absorbed this solar energy in pre-biotic earth would have had the natural
tendency to reduce their energy states back toward zero, since an inherent property of any
entity, including the elements, is that if it is raised to a higher energy level it will
naturally desire to return to its resting energy state. Thus, elements in pre-biotic earth
that absorbed external energy and were raised to higher energy states would have had the
innate desire to reduce their energy states back toward zero.

Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
A simplified way that may help to conceptualize this idea, is if you imagine a ball
resting on top of a hill, which represents elements on pre-biotic earth that have been
raised to higher energy levels via an external energy source. At the top of the hill the ball
has a higher potential energy than at the bottom, just as elements that have been exposed
to an external energy source have a higher potential energy than elements that have not.
Since any entity has the natural desire to decrease its stored potential energy, the ball will
have the natural desire to roll down to the bottom of the hill in order to decrease its stored
potential energy. Of course, the ball naturally rolls down the hill due to the force of
gravity, which is why it is included in the equation for potential energy. Potential energy
is directly proportional to the mass of the ball x the force of gravity x the height at which
the ball is at. As the ball naturally rolls down the hill its stored potential energy will
decrease toward zero and will be equal to zero when the ball reaches the bottom of the
hill. The elements in pre-biotic earth that absorbed external energy would behave just as
the ball did, in the sense that they would have had the inherent desire to reduce their
stored potentil energy toward zero.
An intrinsic property of enzymes, in general, is that they lower the activation
energy (Ea) of chemical reactions, which is the minimum amount of energy that must be
put into a chemical reaction in order for the reaction to proceed and is measured in
kilojoules per mole [1]. For instance, imagine a particular reaction that requires 100
Kj/mol of energy in order for the reaction to proceed. In the absence of an enzyme that
catalyzes this reaction, the minimum amount of energy required for the reaction to occur
would still be 100 kj/mol, however, in the presence of an enzyme capable of catalyzing
this reaction the minimum amount of energy required would decrease to, lets say 50

Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
kj/mol. In other words, in the absence of an enzyme 100 kj/mol of energy was required
for the reaction to proceed, but in the presence of an enzyme only 50 kj/mol of energy
was needed. Thus, it should seem almost intuitive that by lowering the activation energy
of chemical reactions, enzymes would have provided the path of least resistance for
molecules in pre-biotic earth to go from higher to lower states of energy.

Figure 1: Depicts an exergonic reaction in which the products contain less stored potential energy than the
reactants. The orange line is the activation energy in the absence of an enzyme, while the red, dotted line is
the activation energy in the presence of an enzyme. As can be seen, enzymes lower the activation energy
necessary for products to go from higher to lower states of energy.

In order to further illustrate the concept that by lowering the activation energy of
chemical reactions, enzymes provide the path of least resistance for molecules to go from
higher to lower states of energy. Visualize the ball on top of the hill once again,
however, this time imagine a 20 ft wall that blocks the downslope on one half of the hill
and a slip and slide that leads straight to the bottom on the other half. To travel down the
half of the hill containing the wall, 100 kj of energy would need to be put into lifting the
ball over the wall before it could freely roll down the hill. On the other hand, the energy
required to get the ball rolling down the slip and slide-side is only 10 kj. As a result, the
ball will require a mere nudge to get it rolling down slip and slide side of the hill. Thus,

Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
the ball will travel down the path of least resistance, i.e., the slip and slide, since the
required energy for the ball to get rolling down this half of the hill is only 10 kj, while the
energy required to get the ball rolling down the other half is 100 kj. In other words, the
energy necessary to get the ball rolling down the side of the hill with the slip and slide is
90 kj less than the energy necessary to get the ball rolling down the side of the hill with
the wall and as a result, the ball will roll down the slip and slide-side.
Picture this same scenario again, except this time add Donkey Kong to the top of
the hill, who in this example is intended to represent an enzyme and the influence an
enzyme can have over the activation energy and in determining which path is the path of
least resistance. Atop the hill, Donkey Kong spontaneously decides to demolish the wall
and add another slip and slide covered in Crisco . After DKs renovation, the energy
required to get the ball rolling down his side of the hill is now only 1 kj, while the energy
required on the opposite, non-Crisco slip and slide-side is still 10 kj. Now the ball will
roll down the side of the hill with the Crisco-covered slip and slide, because the energy
required to get the ball rolling down this side of the hill is 9 kj less than the energy
required to get the ball rolling down the Crisco-less slip and slide-side. Donkey Kong in
this example reduced the amount of energy that needed to be put into getting the ball to
roll down the hill, just as enzymes reduce the amount of energy that needs to be put into a
chemical reaction in order for it to proceed.
The previous example was intended to connect the three primary ideas discussed
so far. These being that elements naturally desire to go from higher energy states to
lower energy states, elements will reduce their stored potential energy via the path of
least resistance, and that enzymes can provide the path of least resistance by lowering

Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
input energy necessary in order for them to do so. Since enzymes provide the path of
least resistance, than it seems likely that if enzymes were indeed present in pre-biotic
earth that they were the preferred or primary mode by which elements would have reduce
their energy states.
Now seems to be an appropriate time to introduce the next enzymatic trait; which
is that enzymes are not consumed in the reactions they catalyze [3]. This inherent
enzymatic property is of importance here, because it provides a continuous nondisappearing entity with which reactants and products of catalyzed reactions could
become associated. Thus, since enzymes were likely the primary mode for elements to
reduce their energy states in pre-biotic earth, are not consumed in the reactions they
catalyze and since different reactions involve and produce different reactants and
products, than an enzyme could serve as an entity with which these varying reactants and
products could become associated.
Association of these products and reactants with the enzyme(s) catalyzing their
production could provide enzymes with features similar to those of cells today. It is
difficult to say exactly when enough cellular features have become associated with an
enzyme or any other entity to constitue it being considerd a cell, because there is a
continuum between two. In other words, exactly how many features need to accumulate
or need to be present in order for an entity to be considered a cell? That question could
be debated for centuries, however thats not the point. The point is, that enzymes could
become associated with reactants and products that are similar to the cells of today.
For instance, imagine an enzyme or a set of enzymes, which catalyze a reaction
that forms phospholipids as a product. It has actually been found that phospholipids of

Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
the correct length can spontaneously form phospholipid bilayers, which is the main
component of any cell membrane [4]. Actuallly, the production of phospholipids can in
fact be mediated by the enzyme phospholipase, as represented in the following
stochiometric eqtuation: Amino Acids (phospholipase) Phospholipids [5]. Since
phospholipase is not consumed in the reaction that it catalyzes, the phospholipids could
potentially become associated with the enzyme phospholipase, which is catalyzing their
synthesis. Potentially, if enough phospholipids of the correct length were produced and
became associated with the enzyme phospholipase, they could eventually spontaneously
form a phospholipid bilayer around the enzyme; which is the most basic component of
the cell membrane.
The previous example pertained to an enzyme catalyzing the production of
phospholipids. The idea that the products of catalyzed reactions become associated with
the enzyme catalyzing their synthesis is surely not limited to just phospholipids. There
are a wide variety of enzymes that catalyze a wide variety of chemical reactions, which
yield a wide variety of products. In theory, all reactants and products involved in
enzyme-mediated reactions could become associated with the enzyme mediating the
reaction, resulting in the emergence of properties associated with the enzyme that could
provide enzymes with an evolutionary advantage over other entities in the origin of life.
Since ribozomes also provide the path of least resistance and are not consumed in
the reactions they catalyze, than theoretically reactants and products could have become
associated with them, providing them with cellular features and an evolutionary
advantage over other entities in the origin of life. However, due to the limited number of
reactions they catalyze, the difficulty synthesizing their building blocks, and their relative

Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
unstability relative to enzymes, it does not seem very likely that this would have been the
case.
It is thought that earths early environment was initially O2-poor, which would
have allowed for the development of organic molecules, since O2 degrades any organic
molecule that it comes in contact with. It is thought that in pre-biotic earth O2 was being
produced, however, any O2 emitted into the atmosphere was absorbed by organic matter
and iron; which inhibited O2 from accumulating in the atmosphere . It was not until
earths organic matter and iron became saturated with O2, that O2 was able to
accumulate in the atmosphere. The period in earths history at which its organic matter
and iron became saturated with oxygen and oxygen began accumulating in earths
environment is known as the Great Oxygenation Event (GOE). Thus, since O2 degrades
any organic molecule it comes in contact with, it should seem apparent that before the
GOE, O2 was not present in high enough concentrations to inhibit the formation of
organic molecules, but after the GOE, O2 was able to accumulate and inhibit their
formation. Thus, it seems likely that before the GOE is when organic molecules such as
enzymes were able to develop freely, since earths oxygen-rich environment after the
GOE would have inhibited the formation of these molecules.
How is the environment before and after the GOE relevant to this alternative
abiogenic theory? Well, if before the GOE was in fact when there was the most
formation of enzymes and if the products of a catalyzed reaction can become associated
with the catalyst itself, than an enzyme or a set of enzymes could become associated with
the products of the reactions they catalyze that would provide them with protection from
the O2-rich environment after the GOE. The example mentioned earlier in which

Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
phospholipids of the correct length spontaneously formed a phospholipid bilayer seems
of upmost importance here. Once again, catalysis of a reaction resulting the production
of phospholipids that spontaneously form a phospholipid bilayer could become associated
with the enzyme that is catalyzing the phospholipid-producing reaction, which would
provide protection from the degradive effects of oxygen after the GOE.
Enzymes are also directly involved in endergonic reactions, which increase the
stored potential energy in the product(s). Initially, the fact that enzymes also mediate
increases in stored potential energy seemed somewhat contradictory to the present
theory, since it is built off of the idea that enzymes provide the path of least resistance for
elements to decrease their energy states. It is still true that entities have the natural desire
to reduce their energy states, however, since external energy can enter earths system,
entities can also be raised in energy levels. Enzymes still provide the path of least
resistance by lowering the activation energy of the reaction, only instead of lowering the
activation energy for elements to go from higher to lower states of energy, they lower the
activation energy for elements to go from lower to higher states of energy.

Figure 2. Depicts the activation energy necessary for a reaction to increase its stored potential energy in the
presence vs. in the absence of an enzyme. As can be seen, the activation energy or amount of input energy
necessary for the reaction to proceed is reduced in the presence of an enzyme.

Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
As was previously mentioned, since enzymes lower the activation energy and
provide the path of least resistance, one would expect that that they would be the primary
mode by which elements decrease, as well as increase their energy states. This enzymatic
traits is applicable to the current theory, because it provides enzymes with the ability to
store potential energy (endergonic reaction) as well as use stored potential energy when
needed (exergonic reaction), just like the organisms of today. Once again, based on the
limited number of reactions that ribozomes are able to catalyze, than they would have
become associated with fewer reactants and products containing stored potential energy
relative to enzymes. Thus, it seems more likely that the stored forms of energy found in
organisms today, such as glycogen and triglycerides, are due to enzymes, instead of RNA
- as a matter of fact, the synthesis of the energy-storing molecules is directly mediated by
enzymes in organisms today.
Enzymes are also highly involved in the transcription and translation of DNA and
RNA, so in theory, enzymes could have been responsible for the development of DNA
and/or RNA and not the other way around. For instance, the enzyme DNA helicase
unwinds DNA prior to translation, while the enzyme DNA polymerase carries out the
actual translation of DNA into RNA [6]. Since enzymes, DNA, and RNA are all highly
involved in the basic functioning of an organism, the argument as to which came first
could be compared/reduced to the chicken or the egg paradox, in the sense that what
developed first, DNA, RNA or enzymes?
Fewer interactions between RNA and pre-biotic elements suggests that RNA
would have had fewer reactants and substrates with which is associated compared to
enzymes. Conversely, a high interaction between enzymes and pre-biotic elements

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Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
suggests that enzymes would have had more substrates and products with which they
could become associated. Therefore, if more substrates and products became associated
with an enzyme in pre-biotic earth relative to RNA, than one would expect that the
number of substrates and products associated with an enzyme would also be greater
relative to RNA. This increased association of substrates and products with enzymes
could provide them with an evolutionary advantage over other entities, such as RNA, in
the origin of life.
The RNA World Theory in particular which presents a strong counterpoint to the
enzyme-first world model. This being that the RNA World Theory hypothesis cites
subtypes of RNA known as ribozymes that are themselves capable of catalyzing reactions
[7]. Thus, RNA also could have provided the path of least resistance for molecules to
increase and decrease their energy states and could have become associated with
reactants and products of RNA-catalyzed reactions. However, there are two primary
reasons why enzymes appear to have pre-dated the formation of all subtypes of RNA
capable of catalyzing chemical reactions. First, RNA is a highly unstable molecule and is
easily broken down when subjected to the degradive effects of earths environment and
secondly, the reactions which RNA is capable of catalyzing are significantly less [8],
compared to the reactions that enzymes are capable of catalyzing.
Due to RNAs unstable molecular structure and the minute number of reactions
that it is involved in, it seems unlikely that RNA would have been the predominant entity
in pre-biotic earth. RNAs inability to catalyze the same number of reactions that
enzymes are capable of catalyzing would have provided RNA with fewer reactants and
products with which it could have become associated with, thus providing RNA with a

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Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
reduced evolutionary advantage over other entities, such as enzymes. For instance, no
RNA strand has been found that catalyzes the production of phospholipids, which could
provide RNA with protection from the degradive effects of earths environment after the
GOE.
Enzymes on the other hand are capable of catalyzing the production of
phospholipids; which could have provided them with protection from earths
environment after the GOE. Ultimately, since enzymes are involved in a greater number
of reactions which involve a greater variety of reactants and products compared to RNA,
than a greater number of reactants and products formed via enzymes would have been
available to become associated with enzymes, thus providing them with an evolutionary
advantage over other entities in the formation of life, such as RNA.
The current theory is not intended to argue that RNA did not precede the
formation of DNA, but rather, to discredit the RNA World Hypothesis theory that RNA
preceded the formation of enzymes [9]. The enzyme-first model seems more plausible
based on the previously-mentioned inherent enzymatic characteristics; such as lowering
the activation energy of chemical reactions, providing the path of least resistance for
molecules to go from higher to lower or from lower to higher states of energy, they are
not consumed in the reactions they catalyze, they directly mediate increases and
decreases in stored potential energy, and are highly involved in the translation and
transcription of DNA and RNA. RNA on the other hand is highly unstable, does not
typically lower the activation energy of chemical reactions, does not provide the path of
least resistance and mediates fewer chemical reactions compared to enzymes. Ultimately
it is the association of the products with the catalyst that provides them with an

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Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
evolutionary advantage. Thus, since RNA is capable of catalyzing fewer reactions
relative to enzymes, than fewer products would have been available to become associated
with RNA-type catalysts and they would have had a reduced evolutionary advantage
compared to enzymes, which is why it seems likely that enzymes formed prior to RNA in
the origin of life.
It may seem unlikely at first that something such as water taking the path of least
resistance down an incline over billions of years could shape the landscape to the degree
it has today. However, water taking the path of least resistance to reduce its stored
potential energy has indeed drastically shaped earths terrain, as can be seen in the
formation of the vast and deep ravines associated with the Grand Canyon, which formed
from the Colorado River. Water at higher elevations, like the headwaters of the Colorado
River, contain stored potential energy just as elements in pre-biotic earth that absorbed
electromagnetic waves from the sun would have possessed stored potential energy. Now
ask yourself the following question. What specifically was altered and developed
characteristics due to water flowing from higher to lower ground? The answer, it was the
path of least resistance or the route that the water took to reduce its stored potential
energy, which is exactly what the current theory is trying to argue happened with
enzymes. Except, instead of the path of least resistance being the path carved by the
Colorado River, as is the case for the Grand Canyon, the path of least resistance for
elements/molecules in pre-biotic earth to reduce their energy states would have been
enzymes. The development and features of the Grand Canyon formed due to water
taking the path of least resistance, just as the development and features associated with

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Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
organisms today could have formed due to elements/molecules in pre-biotic earth taking
the path of least resistance from higher to lower energy states i.e., enzymes.

Citations
1) Nowick, J., Rebek, J., et. al. (1991) Kinetic Studies & Modeling of a SelfReplicating System. [Electronic Version] Critical Views in Biochemistry and
Molecular Biology. 113, 8821-8839

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Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
2) Kuchner, O., Arnold, F. (1998, February 3) Directed Evolution of Enzyme
Catalysts. [Electronic version]. Trends in Biotechnology (15)12, 523-530
3) Lionnet Timothee., Michelle M. Spiering., et. al. (2007) Real-Time obseration of
bacteriophage T4 gp41 helicase reveals an unwinding mechanism. [Electronic
Version]. National Academy of Sciences of the USA. 110, 11-31
4) Siewart, Marrink., Lindahl, Erik., et. al. (2001, August 10). Simulation of the
Spontaneous Aggregation of Phospholipids Into Bilayers. [Electronic version].
Journal of the American Chemical Society. 123(35), 8638-8639
5) Verkleij, A., Zwaai, R., et al., (1973, May 23). The asymmetric distribution of
phospholipids in the human red cell membrane: A combined study using
phospholipases and freeze-etch electron microscopy. [Electronic Version].
Biochimica et Biophysica Acta (BBA) Biomembranes. 323(2), 178-193.
6) Lionnet Timothee., Michelle M. Spiering., et. al. (2007) Real-Time obseration of
bacteriophage T4 gp41 helicase reveals an unwinding mechanism. National
Academy of Sciences of the USA. 110, 11-31
7) Gilbert, Walter., (1986, February 20). Origin of Life: The RNA World.
[Electronic Version]. Nature. 319, 618.
8) Turk, Rebecca., Chumachenko, Nataliya., (2010, January 27). Multiple
Translational Products from a Five-Nucleotide Ribozyme. [Electronic Version]
Proceedings of the National Academy of Sciences of the United States of America.
107(10), 4585-4589.

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Erik Daniel Majcher

IPHY 3700: Marie Boyko

Submitted 11-23-2010
9) Orgel, Leslie. (2004) Prebiotic Chemistry and the Origin of the RNA World.
[Electronic Version]. Critical Views in Biochemistry and Molecular Biology. 39,
99-123.

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