Zygosity (the noun, zygote, is from the Greek zygotos "yoked," from zygon "yoke") (/zaɪˈɡɒsɪti/) is the degree of similarity of the alleles for a trait in an organism.
Most eukaryotes have two matching sets of chromosomes; that is, they are diploid. Diploid organisms have the same loci on each of their two sets of homologous chromosomes
except that the sequences at these loci may differ between the two
chromosomes in a matching pair and that a few chromosomes may be
mismatched as part of a chromosomal sex-determination system. If both alleles of a diploid organism are the same, the organism is homozygous at that locus. If they are different, the organism is heterozygous at that locus. If one allele is missing, it is hemizygous, and, if both alleles are missing, it is nullizygous.
The DNA sequence of a gene often varies from one individual to another. Those variations are called alleles.
While some genes have only one allele because there is low variation,
others have only one allele because deviation from that allele can be
harmful or fatal. But most genes have two or more alleles. The frequency
of different alleles varies throughout the population. Some genes may
have two alleles with equal distribution. For other genes, one allele
may be common, and another allele may be rare. Sometimes, one allele is a
disease-causing
variation while the other allele is healthy. Sometimes, the different
variations in the alleles make no difference at all in the function of
the organism.
In diploid organisms, one allele is inherited from the male
parent and one from the female parent. Zygosity is a description of
whether those two alleles have identical or different DNA sequences. In
some cases the term "zygosity" is used in the context of a single
chromosome.
Types
The words homozygous, heterozygous, and hemizygous are used to describe the genotype of a diploid organism at a single locus on the DNA. Homozygous describes a genotype consisting of two identical alleles at a given locus, heterozygous describes a genotype consisting of two different alleles at a locus, hemizygous describes a genotype consisting of only a single copy of a particular gene in an otherwise diploid organism, and nullizygous refers to an otherwise-diploid organism in which both copies of the gene are missing.
Homozygous
A cell is said to be homozygous for a particular gene when identical alleles of the gene are present on both homologous chromosomes. The cell or organism in question is called a homozygote. True breeding organisms are always homozygous for the traits that are to be held constant.
An individual that is homozygous-dominant for a particular trait carries two copies of the allele that codes for the dominant
trait. This allele, often called the "dominant allele", is normally
represented by a capital letter (such as "P" for the dominant allele
producing purple flowers in pea plants). When an organism is
homozygous-dominant for a particular trait, the genotype is represented
by a doubling of the symbol for that trait, such as "PP".
An individual that is homozygous-recessive for a particular trait carries two copies of the allele that codes for the recessive trait.
This allele, often called the "recessive allele", is usually
represented by the lowercase form of the letter used for the
corresponding dominant trait (such as, with reference to the example
above, "p" for the recessive allele producing white flowers in pea
plants). The genotype of an organism that is homozygous-recessive for a
particular trait is represented by a doubling of the appropriate letter,
such as "pp".
Heterozygous
A diploid organism is heterozygous at a gene locus when its cells contain two different alleles (one wild-type allele and one mutant allele) of a gene. The cell or organism is called a heterozygotespecifically
for the allele in question, and therefore, heterozygosity refers to a
specific genotype. Heterozygous genotypes are represented by a capital
letter (representing the dominant/wild-type allele) and a lowercase
letter (representing the recessive/mutant allele), such as "Rr" or "Ss".
Alternatively, a heterozygote for gene "R" is assumed to be "Rr". The
capital letter is usually written first.
If the trait in question is determined by simple (complete)
dominance, a heterozygote will express only the trait coded by the
dominant allele, and the trait coded by the recessive allele will not be
present. In more complex dominance schemes the results of heterozygosity can be more complex.
A heterozygous genotype can have a higher relative fitness than
either the homozygous dominant or homozygous recessive genotype – this
is called a heterozygote advantage.
Hemizygous
A chromosome in a diploid organism is hemizygous when only one copy is present.[2] The cell or organism is called a hemizygote. Hemizygosity is also observed when one copy of a gene is deleted, or, in the heterogametic sex, when a gene is located on a sex chromosome. Hemizygosity must not be confused with haploinsufficiency,
which describes a mechanism for producing a phenotype. For organisms in
which the male is heterogametic, such as humans, almost all X-linked
genes are hemizygous in males with normal chromosomes, because they have
only one X chromosome and few of the same genes are on the Y chromosome. Transgenic mice generated through exogenous DNA microinjection of an embryo's pronucleus
are also considered to be hemizygous, because the introduced allele is
expected to be incorporated into only one copy of any locus. A
transgenic individual can later be bred to homozygosity and maintained
as an inbred line to reduce the need to confirm the genotype of each
individual.
In cultured mammalian cells, such as the Chinese hamster ovary cell
line, a number of genetic loci are present in a functional hemizygous
state, due to mutations or deletions in the other alleles.
Nullizygous
A
nullizygous organism carries two mutant alleles for the same gene. The
mutant alleles are both complete loss-of-function or 'null' alleles, so
homozygous null and nullizygous are synonymous. The mutant cell or organism is called a nullizygote.
Autozygous and allozygous
Zygosity
may also refer to the origin(s) of the alleles in a genotype. When the
two alleles at a locus originate from a common ancestor by way of
nonrandom mating (inbreeding), the genotype is said to be autozygous.
This is also known as being "identical by descent", or IBD. When the
two alleles come from different sources (at least to the extent that the
descent can be traced), the genotype is called allozygous. This is known as being "identical by state", or IBS.
Because the alleles of autozygous genotypes come from the same
source, they are always homozygous, but allozygous genotypes may be
homozygous too. Heterozygous genotypes are often, but not necessarily,
allozygous because different alleles may have arisen by mutation some
time after a common origin. Hemizygous and nullizygous genotypes do not
contain enough alleles to allow for comparison of sources, so this
classification is irrelevant for them.
Monozygotic and dizygotic twins
As discussed above, "zygosity" can be used in the context of a specific genetic locus (example). The word zygosity may also be used to describe the genetic similarity or dissimilarity of twins. Identical twins are monozygotic, meaning that they develop from one zygote that splits and forms two embryos. Fraternal twins are dizygotic because they develop from two separate eggs that are fertilized by two separate sperms.
Heterozygosity in population genetics
Heterozygosity values of 51 worldwide human populations. Sub-Saharan Africans have the highest values in the world.
In population genetics,
the concept of heterozygosity is commonly extended to refer to the
population as a whole, i.e., the fraction of individuals in a population
that are heterozygous for a particular locus. It can also refer to the
fraction of loci within an individual that are heterozygous.
Typically, the observed () and expected () heterozygosities are compared, defined as follows for diploid individuals in a population:
Observed
where is the number of individuals in the population, and are the alleles of individual at the target locus.
Expected
where is the number of alleles at the target locus, and is the allele frequency of the allele at the target locus.
The supercritical water reactor (SCWR) is a concept Generation IV reactor, mostly designed as light water reactor (LWR) that operates at supercritical pressure (i.e. greater than 22.1 MPa). The term critical in this context refers to the critical point of water, and must not be confused with the concept of criticality of the nuclear reactor.
The water heated in the reactor core
becomes a supercritical fluid above the critical temperature of 374 °C,
transitioning from a fluid more resembling liquid water to a fluid more
resembling saturated steam (which can be used in a steam turbine), without going through the distinct phase transition of boiling.
In contrast, the well-established pressurized water reactors (PWR) have a primary cooling loop of liquid water at a subcritical pressure, transporting heat from the reactor core to a secondary cooling loop, where the steam for driving the turbines is produced in a boiler (called the steam generator).
Boiling water reactors (BWR) operate at even lower pressures, with the boiling process to generate the steam happening in the reactor core.
The supercritical steam generator is a proven technology.
The development of SCWR systems is considered a promising advancement for nuclear power plants because of its high thermal efficiency
(~45 % vs. ~33 % for current LWRs) and simpler design. As of 2012 the
concept was being investigated by 32 organizations in 13 countries.
History
The
super-heated steam cooled reactors operating at subcritical-pressure
were experimented with in both Soviet Union and in the United States as
early as the 1950s and 1960s such as Beloyarsk Nuclear Power Station, Pathfinder and Bonus of GE's Operation Sunrise program. These are not SCWRs. SCWRs were developed from the 1990s onwards.
Both a LWR-type SCWR with a reactor pressure vessel and a CANDU-type SCWR with pressure tubes are being developed.
A 2010 book includes conceptual design and analysis methods such
as core design, plant system, plant dynamics and control, plant startup
and stability, safety, fast reactor design etc.
A 2013 document saw the completion of a prototypical fueled loop test in 2015. A Fuel Qualification Test was completed in 2014.
A 2014 book saw reactor conceptual design of a thermal spectrum
reactor (Super LWR) and a fast reactor (Super FR) and experimental
results of thermal hydraulics, materials and material-coolant
interactions.
Design
Moderator-coolant
The SCWR operates at supercritical pressure. The reactor outlet coolant is supercritical water. Light water is used as a neutron moderator
and coolant. Above the critical point, steam and liquid become the same
density and are indistinguishable, eliminating the need for
pressurizers and steam generators (PWR), or jet/recirculation pumps, steam separators and dryers (BWR).
Also by avoiding boiling, SCWR does not generate chaotic voids
(bubbles) with less density and moderating effect. In a LWR this can
affect heat transfer and water flow, and the feedback can make the
reactor power harder to predict and control. Neutronic and thermal
hydraulic coupled calculation is needed to predict the power
distribution. SCWR's simplification should reduce construction costs and
improve reliability and safety.
A LWR type SCWR adopts water rods with thermal insulation and A CANDU
type SCWR keeps water moderator in a Calandria tank. A fast reactor core
of the LWR type SCWR adopts tight fuel rod lattice as a high conversion
LWR. The fast neutron spectrum SCWR has advantages of a higher power
density, but needs plutonium and uranium mixed oxides fuel which will be
available from reprocessing.
Control
SCWRs would likely have control rods inserted through the top, as is done in PWRs.
Material
The conditions inside an SCWR are harsher than those in LWRs, LMFBRs,
and supercritical fossil fuel plants (with which much experience has
been gained, though this does not include the combination of harsh
environment and intense neutron radiation). SCWRs need a higher standard of core materials (especially fuel cladding) than either of these. R&D focuses on:
The chemistry of supercritical water under radiation (preventing stress corrosion cracking, and maintaining corrosion resistance under neutron radiation and high temperatures)
Dimensional and microstructural stability (preventing embrittlement, retaining strength and creep resistance also under radiation and high temperatures)
Materials that both resist the harsh conditions and do not absorb too many neutrons, which affects fuel economy
Advantages
Supercritical
water has excellent heat transfer properties allowing a high power
density, a small core, and a small containment structure.
The use of a supercriticalRankine cycle with its typically higher temperatures improves efficiency (would be ~45 % versus ~33 % of current PWR/BWRs).
This higher efficiency would lead to better fuel economy and a lighter fuel load, lessening residual (decay) heat.
SCWR is typically designed as a direct-cycle, whereby steam or hot
supercritical water from the core is used directly in a steam turbine.
This makes the design simple. As a BWR is simpler than a PWR, a SCWR is a
lot simpler and more compact than a less-efficient BWR having the same
electrical output. There are no steam separators, steam dryers, internal
recirculation pumps, or recirculation flow inside the pressure vessel.
The design is a once-through, direct-cycle, the simplest type of cycle
possible. The stored thermal and radiologic energy in the smaller core
and its (primary) cooling circuit would also be less than that of either
a BWR's or a PWR's.
Water is liquid at room temperature, cheap, non-toxic and transparent, simplifying inspection and repair (compared to liquid metal cooled reactors).
A heavy-water SCWR could breed fuel from thorium (4x more abundant than uranium), with increased proliferation resistance over plutonium breeders.
Disadvantages
Lower
water inventory (due to compact primary loop) means less heat capacity
to buffer transients and accidents (e.g. loss of feedwater flow or large
break loss-of-coolant accident) resulting in accident and transient temperatures that are too high for conventional metallic cladding.
However, Safety analysis of LWR type SCWR showed that safety criteria
are met at accidents and abnormal transients including total loss of
flow and loss of coolant accident.
No double ended break occurs because of the once-through coolant cycle.
Core is cooled by the induced flow at the loss of coolant accident.
Higher pressure combined with higher temperature and also a
higher temperature rise across the core (compared to PWR/BWRs) result in
increased mechanical and thermal stresses on vessel materials that are
difficult to solve. A LWR type design, reactor pressure vessel inner
wall is cooled by the inlet coolant as a PWR. Outlet coolant nozzles are
equipped with thermal sleeves. A pressure-tube design, where the core
is divided up into smaller tubes for each fuel channel, has potentially
fewer issues here, as smaller diameter tubing can be much thinner than
massive single pressure vessels, and the tube can be insulated on the
inside with inert ceramic insulation so it can operate at low (calandria
water) temperature.
The coolant greatly reduces its density at the end of the core,
resulting in a need to place extra moderator there. A LWR type SCWR
design adopts water rods in the fuel assemblies. Most designs of CANDU
type SCWR use an internal calandria where part of the feedwater flow is
guided through top tubes through the core, that provide the added
moderation (feedwater) in that region. This has the added advantage of
being able to cool the entire vessel wall with feedwater, but results in
a complex and materially demanding (high temperature, high temperature
differences, high radiation) internal calandria and plena arrangement.
Again a pressure-tube design has potentially fewer issues, as most of
the moderator is in the calandria at low temperature and pressure,
reducing the coolant density effect on moderation, and the actual
pressure tube can be kept cool by the calandria water.
Extensive material development and research on supercritical water chemistry under radiation is needed
Special start-up procedures needed to avoid instability before the
water reaches supercritical conditions. Instability is managed by power
to coolant flow rate ratio as a BWR.
A fast SCWR needs a relatively complex reactor core to have a negative void coefficient. But single coolant flow pass core is feasible.
The structure of hemoglobin. The heme cofactor, containing the metal iron, shown in green.
Metalloprotein is a generic term for a protein that contains a metalioncofactor.
A large proportion of all proteins are part of this category. For
instance, at least 1000 human proteins (out of ~20,000) contain
zinc-binding protein domains although there may be up to 3000 human zinc metalloproteins.
Abundance
It is estimated that approximately half of all proteins contain a metal.
In another estimate, about one quarter to one third of all proteins are
proposed to require metals to carry out their functions. Thus, metalloproteins have many different functions in cells, such as storage and transport of proteins, enzymes and signal transduction proteins, or infectious diseases.
The abundance of metal binding proteins may be inherent to the amino
acids that proteins use, as even artificial proteins without
evolutionary history will readily bind metals.
Most metals in the human body are bound to proteins. For instance, the relatively high concentration of iron in the human body is mostly due to the iron in hemoglobin.
Metal concentrations in humans organs (ppm = ug/g ash)
In metalloproteins, metal ions are usually coordinated by nitrogen, oxygen or sulfur centers belonging to amino acid
residues of the protein. These donor groups are often provided by
side-chains on the amino acid residues. Especially important are the imidazole substituent in histidine residues, thiolate substituents in cysteine residues, and carboxylate groups provided by aspartate. Given the diversity of the metalloproteome,
virtually all amino acid residues have been shown to bind metal
centers. The peptide backbone also provides donor groups; these include
deprotonated amides and the amide carbonyl oxygen centers. Lead(II) binding in natural and artificial proteins has been reviewed.
In addition to donor groups that are provided by amino acid residues, many organic cofactors function as ligands. Perhaps most famous are the tetradentate N4macrocyclicligands incorporated into the heme protein. Inorganic ligands such as sulfide and oxide are also common.
Storage and transport metalloproteins
These are the second stage product of protein hydrolysis obtained by treatment with slightly stronger acids and alkalies.
Oxygen carriers
Hemoglobin, which is the principal oxygen-carrier in humans, has four subunits in which the iron(II) ion is coordinated by the planar macrocyclicligandprotoporphyrin IX (PIX) and the imidazole nitrogen atom of a histidine residue. The sixth coordination site contains a water molecule or a dioxygen molecule. By contrast the protein myoglobin, found in muscle cells, has only one such unit. The active site is located in a hydrophobic pocket. This is important as without it the iron(II) would be irreversibly oxidized to iron(III). The equilibrium constant for the formation of HbO2 is such that oxygen is taken up or released depending on the partial pressure of oxygen in the lungs
or in muscle. In hemoglobin the four subunits show a cooperativity
effect that allows for easy oxygen transfer from hemoglobin to
myoglobin.
In both hemoglobin and myoglobin it is sometimes incorrectly stated that the oxygenated species contains iron(III). It is now known that the diamagnetic nature of these species is because the iron(II) atom is in the low-spin state. In oxyhemoglobin the iron atom is located in the plane of the porphyrin ring, but in the paramagneticdeoxyhemoglobin the iron atom lies above the plane of the ring. This change in spin state is a cooperative effect due to the higher crystal field splitting and smaller ionic radius of Fe2+ in the oxyhemoglobin moiety.
Hemerythrin
is another iron-containing oxygen carrier. The oxygen binding site is a
binuclear iron center. The iron atoms are coordinated to the protein
through the carboxylate side chains of a glutamate and aspartate and five histidine residues. The uptake of O2 by hemerythrin is accompanied by two-electron oxidation of the reduced binuclear center to produce bound peroxide (OOH−). The mechanism of oxygen uptake and release have been worked out in detail.
Hemocyanins carry oxygen in the blood of most mollusks, and some arthropods such as the horseshoe crab. They are second only to hemoglobin in biological popularity of use in oxygen transport. On oxygenation the two copper(I) atoms at the active site are oxidized to copper(II) and the dioxygen molecules are reduced to peroxide, O2− 2.
Oxidation and reduction reactions are not common in organic chemistry as few organic molecules can act as oxidizing or reducing agents. Iron(II), on the other hand, can easily be oxidized to iron(III). This functionality is used in cytochromes, which function as electron-transfer vectors. The presence of the metal ion allows metalloenzymes to perform functions such as redox reactions that cannot easily be performed by the limited set of functional groups found in amino acids. The iron atom in most cytochromes is contained in a heme group. The differences between those cytochromes lies in the different side-chains. For instance cytochrome a has a heme a prosthetic group and cytochrome b has a heme b prosthetic group. These differences result in different Fe2+/Fe3+redox potentials such that various cytochromes are involved in the mitochondrial electron transport chain.
Cytochrome P450 enzymes perform the function of inserting an oxygen atom into a C−H bond, an oxidation reaction.
Rubredoxin is an electron-carrier found in sulfur-metabolizing bacteria and archaea. The active site contains an iron ion coordinated by the sulfur atoms of four cysteine residues forming an almost regular tetrahedron. Rubredoxins perform one-electron transfer processes. The oxidation state of the iron atom changes between the +2 and +3 states. In both oxidation states the metal is high spin, which helps to minimize structural changes.
Plastocyanin is one of the family of blue copper proteins that are involved in electron transfer reactions. The copper-binding site is described as distorted trigonal pyramidal. The trigonal plane of the pyramidal base is composed of two nitrogen atoms (N1 and N2) from separate histidines and a sulfur (S1) from a cysteine. Sulfur (S2)
from an axial methionine forms the apex. The distortion occurs in the
bond lengths between the copper and sulfur ligands. The Cu−S1 contact is shorter (207 pm) than Cu−S2 (282 pm).
The elongated Cu−S2 bonding destabilizes the Cu(II) form and increases the redox potential of the protein. The blue color (597 nm peak absorption) is due to the Cu−S1 bond where S(pπ) to Cu(dx2−y2) charge transfer occurs.
In the reduced form of plastocyanin, His-87 will become protonated with a pKa of 4.4. Protonation prevents it acting as a ligand and the copper site geometry becomes trigonal planar.
Metal-ion storage and transfer
Iron
Iron is stored as iron(III) in ferritin. The exact nature of the binding site has not yet been determined. The iron appears to be present as a hydrolysis product such as FeO(OH). Iron is transported by transferrin whose binding site consists of two tyrosines, one aspartic acid and one histidine. The human body has no mechanism for iron excretion. This can lead to iron overload problems in patients treated with blood transfusions, as, for instance, with β-thalassemia. Iron is actually excreted in urine and is also concentrated in bile which is excreted in feces.
Copper
Ceruloplasmin is the major copper-carrying
protein in the blood. Ceruloplasmin exhibits oxidase activity, which is
associated with possible oxidation of Fe(II) into Fe(III), therefore
assisting in its transport in the blood plasma in association with transferrin, which can carry iron only in the Fe(III) state.
Calcium
Osteopontin is involved in mineralization in the extracellular matrices of bones and teeth.
Metalloenzymes
Metalloenzymes all have one feature in common, namely that the metal ion is bound to the protein with one labilecoordination site. As with all enzymes, the shape of the active site is crucial. The metal ion is usually located in a pocket whose shape fits the substrate. The metal ion catalyzes reactions that are difficult to achieve in organic chemistry.
A reaction similar to this is almost instantaneous with carbonic anhydrase. The structure of the active site in carbonic anhydrases is well known from a number of crystal structures. It consists of a zinc ion coordinated by three imidazole nitrogen atoms from three histidine units. The fourth coordination site is occupied by a water molecule. The coordination sphere of the zinc ion is approximately tetrahedral. The positively-charged zinc ion polarizes the coordinated water molecule, and nucleophilic
attack by the negatively-charged hydroxide portion on carbon dioxide
(carbonic anhydride) proceeds rapidly. The catalytic cycle produces the
bicarbonate ion and the hydrogen ion as the equilibrium
H2CO3 ⇌ HCO− 3 + H+
favours dissociation of carbonic acid at biological pH values.
Vitamin B12-dependent enzymes
The cobalt-containing Vitamin B12 (also known as cobalamin) catalyzes the transfer of methyl (−CH3) groups between two molecules, which involves the breaking of C−C bonds, a process that is energetically expensive in organic reactions. The metal ion lowers the activation energy for the process by forming a transient Co−CH3 bond. The structure of the coenzyme was famously determined by Dorothy Hodgkin and co-workers, for which she received a Nobel Prize in Chemistry. It consists of a cobalt(II) ion coordinated to four nitrogen atoms of a corrin ring and a fifth nitrogen atom from an imidazole group. In the resting state there is a Co−C sigma bond with the 5′ carbon atom of adenosine. This is a naturally occurring organometallic compound, which explains its function in trans-methylation reactions, such as the reaction carried out by methionine synthase.
Nitrogenase (nitrogen fixation)
The fixation of atmospheric nitrogen is a very energy-intensive process, as it involves breaking the very stable triple bond between the nitrogen atoms. The enzyme nitrogenase is one of the few enzymes that can catalyze the process. The enzyme occurs in Rhizobiumbacteria. There are three components to its action: a molybdenum atom at the active site, iron–sulfur clusters that are involved in transporting the electrons needed to reduce the nitrogen, and an abundant energy source in the form of magnesiumATP. This last is provided by a symbiotic relationship between the bacteria and a host plant, often a legume. The relationship is symbiotic because the plant supplies the energy by photosynthesis and benefits by obtaining the fixed nitrogen. The reaction may be written symbolically as
where Pi stands for inorganic phosphate. The precise structure of the active site has been difficult to determine. It appears to contain a MoFe7S8 cluster that is able to bind the dinitrogen molecule and, presumably, enable the reduction process to begin. The electrons are transported by the associated "P" cluster, which contains two cubical Fe4S4 clusters joined by sulfur bridges.
Superoxide dismutase
Structure of a human superoxide dismutase 2 tetramer
The superoxide ion, O− 2 is generated in biological systems by reduction of molecular oxygen. It has an unpaired electron, so it behaves as a free radical. It is a powerful oxidizing agent. These properties render the superoxide ion very toxic and are deployed to advantage by phagocytes to kill invading microorganisms. Otherwise, the superoxide ion must be destroyed before it does unwanted damage in a cell. The superoxide dismutase enzymes perform this function very efficiently.
In biology this type of reaction is called a dismutation reaction. It involves both oxidation and reduction of superoxide ions. The superoxide dismutase (SOD) group of enzymes increase the rate of reaction to near the diffusion-limited rate.
The key to the action of these enzymes is a metal ion with variable
oxidation state that can act either as an oxidizing agent or as a
reducing agent.
Oxidation: M(n+1)+ + O− 2 → Mn+ + O2
Reduction: Mn+ + O− 2 + 2 H+ → M(n+1)+ + H2O2.
In human SOD the active metal is copper, as Cu(II) or Cu(I), coordinated tetrahedrally by four histidine residues. This enzyme also contains zinc ions for stabilization and is activated by copper chaperone for superoxide dismutase (CCS). Other isozymes may contain iron, manganese or nickel.
Ni-SOD is particularly interesting as it involves nickel(III), an
unusual oxidation state for this element. The active site nickel
geometry cycles from square planar Ni(II), with thiolate (Cys2 and Cys6) and backbone nitrogen (His1 and Cys2) ligands, to square pyramidal Ni(III) with an added axial His1 side chain ligand.
Chlorophyll-containing proteins
Hemoglobin (left) and chlorophyll
(right), two extremely different molecules when it comes to function,
are quite similar when it comes to its atomic shape. There are only
three major structural differences; a magnesium atom (Mg) in chlorophyll, as opposed to iron (Fe) in hemoglobin. Additionally, chlorophyll has an extended isoprenoid tail and an additional aliphatic cyclic structure off the macrocycle.
Chlorophyll plays a crucial role in photosynthesis. It contains a magnesium enclosed in a chlorin
ring. However, the magnesium ion is not directly involved in the
photosynthetic function and can be replaced by other divalent ions with
little loss of activity. Rather, the photon is absorbed by the chlorin ring, whose electronic structure is well-adapted for this purpose.
Initially, the absorption of a photon causes an electron to be excited into a singlet state of the Q band. The excited state undergoes an intersystem crossing from the singlet state to a triplet state in which there are two electrons with parallel spin. This species is, in effect, a free radical, and is very reactive and allows an electron to be transferred to acceptors that are adjacent to the chlorophyll in the chloroplast.
In the process chlorophyll is oxidized. Later in the photosynthetic
cycle, chlorophyll is reduced back again. This reduction ultimately
draws electrons from water, yielding molecular oxygen as a final
oxidation product.
Hydrogenase
Hydrogenases are subclassified into three different types based on
the active site metal content: iron–iron hydrogenase, nickel–iron
hydrogenase, and iron hydrogenase.
All hydrogenases catalyze reversible H2 uptake, but while the [FeFe] and [NiFe] hydrogenases are true redoxcatalysts, driving H2 oxidation and H+ reduction
H2 ⇌ 2 H+ + 2 e−
the [Fe] hydrogenases catalyze the reversible heterolytic cleavage of H2.
H2 ⇌ H+ + H−
The active site structures of the three types of hydrogenase enzymes.
Ribozyme and deoxyribozyme
Since discovery of ribozymes by Thomas Cech and Sidney Altman in the early 1980s, ribozymes have been shown to be a distinct class of metalloenzymes.
Many ribozymes require metal ions in their active sites for chemical
catalysis; hence they are called metalloenzymes. Additionally, metal
ions are essential for structural stabilization of ribozymes. Group I intron is the most studied ribozyme which has three metals participating in catalysis. Other known ribozymes include group II intron, RNase P, and several small viral ribozymes (such as hammerhead, hairpin, HDV, and VS) and the large subunit of ribosomes. Recently, four new classes of ribozymes have been discovered (named twister, twister sister, pistol and hatchet) which are all self-cleaving ribozymes.
Deoxyribozymes, also called DNAzymes or catalytic DNA, are artificial catalytic DNA molecules that were first produced in 1994 and gained a rapid increase of interest since then. Almost all DNAzymes
require metal ions in order to function; thus they are classified as
metalloenzymes. Although ribozymes mostly catalyze cleavage of RNA
substrates, a variety of reactions can be catalyzed by DNAzymes
including RNA/DNA cleavage, RNA/DNA ligation, amino acid phosphorylation
and dephosphorylation, and carbon–carbon bond formation.
Yet, DNAzymes that catalyze RNA cleavage reaction are the most
extensively explored ones. 10-23 DNAzyme, discovered in 1997, is one of
the most studied catalytic DNAs with clinical applications as a
therapeutic agent. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific), the CA1-3 DNAzymes (copper-specific), the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific).
Signal-transduction metalloproteins
Calmodulin
EF-hand motif
Calmodulin is an example of a signal-transduction protein. It is a small protein that contains four EF-hand motifs, each of which is able to bind a Ca2+ ion.
In an EF-hand loop the calcium ion is coordinated in a pentagonal bipyramidal configuration. Six glutamic acid and aspartic acid
residues involved in the binding are in positions 1, 3, 5, 7 and 9 of
the polypeptide chain. At position 12, there is a glutamate or aspartate
ligand that behaves as a (bidentate ligand), providing two oxygen
atoms. The ninth residue in the loop is necessarily glycine
due to the conformational requirements of the backbone. The
coordination sphere of the calcium ion contains only carboxylate oxygen
atoms and no nitrogen atoms. This is consistent with the hard nature of the calcium ion.
The protein has two approximately symmetrical domains, separated
by a flexible "hinge" region. Binding of calcium causes a conformational
change to occur in the protein. Calmodulin participates in an intracellular signaling system by acting as a diffusible second messenger to the initial stimuli.
Troponin
In both cardiac and skeletal muscles, muscular force production is controlled primarily by changes in the intracellular calciumconcentration. In general, when calcium rises, the muscles contract and, when calcium falls, the muscles relax. Troponin, along with actin and tropomyosin, is the protein complex to which calcium binds to trigger the production of muscular force.
Many transcription factors contain a structure known as a zinc finger, this is a structural module where a region of protein folds around a zinc ion. The zinc does not directly contact the DNA that these proteins bind to. Instead, the cofactor is essential for the stability of the tightly-folded protein chain. In these proteins, the zinc ion is usually coordinated by pairs of cysteine and histidine side-chains.
Other metalloenzymes
There are two types of carbon monoxide dehydrogenase:
one contains iron and molybdenum, the other contains iron and nickel.
Parallels and differences in catalytic strategies have been reviewed.
