Metals in Biology
Content
UNIVERSITI KEBANGSAAN MALAYSIA
Metals In Biology
Perpared By Zahran Bin Zuheer (A128089)
For Prof. Yang Farina Abdul Aziz
METALS IN BIOLOGY
Metals will rarely be thought of when one talks about biology. However, if one was to look more deeply in the chemistry that happens in most organisms, one will see that within most biological organisms,metlas play an inportant role in some of the more known biological processes such as photosynthesis and even oxygen transportation.
As was stated before, the prcess of oxygen transportation involves the red blood cells which are known as hemoglobin. The active site in hemoglobin is in actuallity an iron atom. The iron atom, acts as the site where the oxygen is bonded to the hemoglobin cell forming oxyhemoglobin. This is then transported through the whole body to cope with the body’s oxygen needs.
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 require metals to carry out their functions. Thus, metalloproteins have many different functions in cells, such as enzymes, transport and storage proteins, and signal transduction proteins.
Iron(II), 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 hemegroup. 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 which is coordinated by the sulphur atoms of four cysteine residues forming an almost regular tetrahedron. Rubredoxins perform oneelectron 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.
Copper proteins have diverse roles in biological electron transport and oxygen transportation, processes that exploit the easy interconversion of Cu(I) and Cu(II). The biological role for copper commenced with the appearance of oxygen in earth's atmosphere. The protein hemocyanin is the oxygen carrier in most mollusks and some arthropods such as the horseshoe crab(Limulus polyphemus). Because hemocyanin is blue, these organisms have blue blood, not the red blood found in organisms that rely on hemoglobin for this purpose. Structurally related to hemocyanin are the laccases and tyrosinases. Instead of reversibly binding oxygen, these proteins hydroxylate substrates, illustrated by their role in the formation of lacquers.
The most important role of the molybdenum in living organisms is as a metal heteroatom at the active site in certain enzymes. In nitrogen fixation in certain bacteria, the nitrogenase enzyme, which is involved in the terminal step of reducing molecular nitrogen, usually contains molybdenum in the active site (though replacement of Mo with iron or vanadium is also known). The structure of the catalytic center of the enzyme is similar to that in iron-sulfur proteins: it incorporates a Fe4S3 and multiple MoFe3S3 clusters.
In 2008, evidence was reported that a scarcity of molybdenum in the Earth's early oceans was a limiting factor for nearly two billion years in the further evolution of eukaryotic life(which includes all plants and animals) as eukaryotes cannot fix nitrogen, and must therefore acquire most of their organic nitrogen from prokaryotic bacteria. The scarcity of molybdenum resulted from the relative lack of oxygen in the early ocean. However, once oxygen dissolved in seawater it helped dissolve molybdenum from minerals on the sea bottom, making it available to nitrogen-fixing bacteria and allowing them to provide more nitrogen for higher forms of life.
Although oxygen once promoted nitrogen fixation via making molybdenum available in water, it also directly poisons nitrogenase enzymes, so that historically, after oxygen arrived in large quantities in Earth's air and water, organisms which continued to fix nitrogen in aerobic conditions were required to isolate their nitrogen-fixing enzymes in heterocysts, or similar structures which protect them from too much oxygen.
The molybdenum cofactor (pictured) contains an organic complex called molybdopterin, which binds an oxidized molybdenum through adjacent sulfur (or occasionally selenium) atoms.
Though molybdenum forms compounds with various organic molecules, including carbohydrates and amino acids, it is transported throughout the human body as MoO42−.[50] At least 50 molybdenum-containing enzymes were known by 2002, mostly in bacteria, and their number is increasing with every year; those enzymes include aldehyde oxidase, sulfite oxidase and xanthine oxidase. In some animals, and in humans, the oxidation of xanthine to uric acid, a process of purine catabolism, is catalyzed by xanthine oxidase, a molybdenumcontaining enzyme. The activity of xanthine oxidase is directly proportional to the amount of molybdenum in the body. However, an extremely high concentration of molybdenum reverses the trend and can act as an inhibitor in both purine catabolism and other processes. Molybdenum concentrations also affect protein synthesis, metabolism and growth.[50]
In animals and plants these enzymes use molybdenum bound at the active site in a tricyclic molybdenum cofactor. All molybdenum-using enzymes so far identified in nature use this cofactor, save for the phylogenetically ancient molybdenum nitrogenases, which fix nitrogen in some bacteria and cyanobacteria.[53] Molybdenum enzymes in plants and animals catalyze the oxidation and sometimes reduction of certain small molecules, as part of the regulation of nitrogen, sulfur and carbon cycles.[54]
The human body contains about 0.07 mg of molybdenum per kilogram of weight.[55] It occurs in higher concentrations in the liver and kidneys and in lower concentrations in the vertebrae.[5] Molybdenum is also present within human tooth enamel and may help prevent its decay.[56]
The average daily intake of molybdenum varies between 0.12 and 0.24 mg, but it depends on the molybdenum content of the food.[57] Pork, lamb and beef liver each have approximately 1.5 parts per million of molybdenum. Other significant dietary sources include green beans, eggs, sunflower seeds, wheat flour, lentils, cucumbers and cereal grain.[6]Acute toxicity has not been seen in humans, and the toxicity depends strongly on the chemical state. Studies on rats show a median lethal dose (LD50) as low as 180 mg/kg for some Mo compounds.[58] Although human toxicity data is unavailable, animal studies have shown that chronic ingestion of more than 10 mg/day of molybdenum can cause diarrhea, growth retardation, infertility, low birth weight and gout; it can also affect the lungs, kidneys and liver.[57][59] Sodium tungstate is a competitive inhibitor of molybdenum. Dietary tungsten reduces the concentration of molybdenum in tissues.[5]
Dietary molybdenum deficiency from low soil concentration of molybdenum has been associated with increased rates of esophageal cancer in a geographical band from northern China to Iran.[60][61] Compared to the United States, which has a greater supply of molybdenum in the soil, people living in these areas have about 16 times greater risk foresophageal squamous cell carcinoma.[62]
Molybdenum deficiency has also been reported as a consequence of non-molybdenum supplemented total parenteral nutrition (complete intravenous feeding) for long periods of time.[citation
needed]
It results in high blood levels of sulfite and urate, in much the same way
as molybdenum cofactor deficiency. However, presumably since pure molybdenum deficiency from this mechanism is seen primarily in adults, the neurological consequences have not been as marked as for the congenital cofactor deficiency.
Copper is also a component of other proteins associated with the processing of oxygen. In cytochrome c oxidase, which is required for aerobic respiration, copper and iron cooperate in the reduction of oxygen. Copper is also found in many superoxide dismutases, proteins that detoxify superoxides, by converting it (by disproportionation) to oxygen and hydrogen peroxide: 2 HO2 → H2O2 + O2
Several copper proteins, such as the "blue copper proteins", do not interact directly with substrates, hence they are not enzymes. These proteins relay electrons by the process called electron transfer.[74]
Plastocyan is one of the family of blue copper proteins which are involved in electron transfer reactions. The copper binding site is described as a ‘distorted trigonal pyramidal’.[13] 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 picometers) than Cu-S2 (282 pm). The elongated Cu-S2 bonding destabilises the CuII form and increases the redox potential of the protein. The blue colour (597 nm peak absorption) is due to the Cu-S1 bond where Spπ to Cudx2-y2 charge transfer occurs.[14]
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.
Most well-nourished people in industrialized countries have 4 to 5 grams of iron in their bodies. Of this, about 2.5 g is contained in the hemoglobin needed to carry oxygen through the blood, and most of the rest (approximately 2 grams in adult men, and somewhat less in women of childbearing age) is contained in ferritin complexes that are present in all cells, but most common in bone marrow, liver, and spleen. The liver's stores of ferritin are the primary physiologic source of reserve iron in the body. The reserves of iron in adults in
industrialized countries tend to be lower in children and women of child-bearing age, than in men and in the elderly. Women who must use their stores to compensate for iron lost throughmenstruation, pregnancy or lactation, have lower body stores, which may consist of 500 mg or even less.
Of the body's total iron content, about 400 mg is devoted to cellular proteins that use iron for important cellular processes like storing oxygen (myoglobin), or performing energyproducing redox reactions (cytochromes). A relatively small amount (3-4 mg) circulates through the plasma, bound to transferrin. [5]. Because of its toxicity, free soluble iron (soluble ferrous ions Fe(II)) is kept in low concentration in the body.
Iron deficiency first attacks the storage iron in the body, and depletion of these stores is thought to be relatively non-symptomatic, although some vague and non-specific symptoms have been associated with it. Since so much iron is required for hemoglobin, iron deficiency anemia is the primary clinical manifestation of iron deficiency. Oxygen transport is so important to human life that severe anemia harms or kills people by depriving their organs of enough oxygen. Iron-deficient people will suffer or die from organ damage well before cells run out of the iron needed for intracellular processes like electron transport.
Macrophages of the reticuloendothelial system store iron as part of the process of breaking down and processing hemoglobin from engulfed red blood cells.
Iron is also stored as a pigment called hemosiderin in an apparently pathologic process. This molecule appears to be mainly the result of cell damage. It is often found engulfed bymacrophages that are scavenging regions of damage. It can also be found among people with iron overload due to frequent blood cell destruction and transfusions.
Organobromine compounds in a number of species of marine algae are generated by the action of a vanadium dependentbromoperoxidase. This is a haloperoxidase in algae which requires bromide and is an absolutely vanadium-dependent enzyme. Most organobromine compounds in the sea ultimately arise via the action of this vanadium bromoperoxidase.[49]
German
chemist
Martin
Henze
discovered squirts) in
vanadium 1911.[50][51] It
in is
the blood essential
cells (or coelomic cells)
of Ascidiacea (sea
to ascidians and tunicates, where it is stored in the highly acidified vacuoles of certain blood cell types, designated vanadocytes.Vanabins (vanadium binding proteins) have been identified in the cytoplasm of such cells. The concentration of vanadium in their blood is up to 10 million times higher than the concentration of vanadium in the seawater around them. The function of this vanadium concentration system, and these vanadium-containing proteins, is still unknown.
A vanadium nitrogenase is used by some nitrogen-fixing micro-organisms, such as Azotobacter. In this role vanadium replaces more common molybdenum or iron, and gives the nitrogenase slightly different properties.[52]
Several species of macrofungi, namely Amanita muscaria and related species, accumulate vanadium (up to 500 mg/kg in dry weight). Vanadium is present in the coordination complex, amavadin,[53] in fungal fruit-bodies. However, the biological importance of the accumulation process is unknown.[54][55] Toxin functions
or peroxidase enzyme functions have been suggested.
Rats and chickens are also known to require vanadium in very small amounts and deficiencies result in reduced growth and impairedreproduction.[56] Vanadium is a relatively controversial dietary supplement, primarily for increasing insulin sensitivity[57] and bodybuilding. Whether it works for the latter purpose has not been proven, and there is some evidence that athletes who take it are merely experiencing a placebo effect.[58] Vanadyl sulfate may improve glucose control in people with type 2 diabetes.[59][60][61][62][63] In addition, decavanadate and oxovanadates are species that potentially have many biological activities and that have been successfully used as tools in the comprehension of several biochemical processes.[64]
The process of photosynthesis also involves metals in its process. Chlorophyll, in leaves of the plants, which make up the 3 necessary parts of photosynthesis, the other two being carbon dioxide and light, actually has a magnesium atom as the center of its chemical structure. Its discovery in the early 1900’s is actually the first time that this particular element was found in a living tissue.
The chemistry of the Mg2+ ion, as applied to enzymes, uses this ion’s chemistry to fulfill a range of functions. Mg2+ interacts with substrates, enzymes and occasionally both (Mg2+ may form part of the active site). Mg2+ generally interacts with substrates through inner sphere coordination, stabilising anions or reactive intermediates, also including binding to ATP and activating the molecule to nucleophilic attack. When interacting with enzymes and other proteins Mg2+ may bind using inner or outer sphere coordination, to either alter the conformation of the enzyme or take part in the chemistry of the catalytic reaction. In either case, because Mg2+ is only rarely fully dehydrated during ligand binding, it may be a water molecule associated with the Mg2+ that is important rather than the ion itself. The Lewis acidity of Mg2+ (pKa 11.4) is used to allow both hydrolysis and condensation reactions (most commonly phosphate ester hydrolysis and phosphoryl transfer) that would otherwise require pH values greatly removed from physiological values.
ATP (adenosine triphosphate), the main source of energy in cells, must be bound to a magnesium ion in order to be biologically active. What is called ATP is often actually MgATP.
Nucleic acids have an important range of interactions with Mg2+. The binding of Mg2+ to DNA and RNA stabilises structure; this can be observed in the increased melting temperature (Tm) of double-stranded DNA in the presence of Mg2+. Additionally, ribosomes contain large amounts of Mg2+ and the stabilisation provided is essential to the complexation of this ribo-protein. A large number of enzymes involved in the biochemistry of nucleic acids bind Mg2+ for activity, using the ion for both activation and catalysis. Finally, the autocatalysis of many ribozymes (enzymes containing only RNA) is Mg2+ dependent (e.g. the yeast mitochondrial group II self splicing introns).
Magnesium ions can be critical in maintaining the positional integrity of closely clustered phosphate groups. These clusters appear in numerous and distinct parts of the cell nucleus and cytoplasm. For instance hexahydrated Mg2+ ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes.
Biological cell membranes and cell walls are polyanionic surfaces. This has important implications for the transport of ions, particularly because it has been shown that different membranes preferentially bind different ions. Both Mg2+ and Ca2+ regularly stabilise membranes by the cross-linking of carboxylated and phosphorylated head groups of lipids. However, the envelope membrane of E. coli has also been shown to bind Na+, K+, Mn2+ and Fe3+. The transport of ions is dependent on both the concentration gradient of the ion and the electric potential (ΔΨ) across the membrane, which will be affected by the charge on the membrane surface. For example, the specific binding of Mg2+ to the chloroplast envelope has been implicated in a loss of photosynthetic efficiency by the blockage of K+ uptake and the subsequent acidification of the chloroplast stroma.
The Mg2+ ion tends to bind only weakly to proteins (Ka ≤ 105[28]) and this can be exploited by the cell to switch enzymatic activity on and off by changes in the local concentration of Mg2+. Although the concentration of free cytoplasmic Mg2+ is on the order of 1 mmol/L, the total Mg2+ content of animal cells is 30 mmol/L[36] and in plants the content of leaf endodermal cells has been measured at values as high as 100 mmol/L (Stelzer et al., 1990), much of which is buffered in storage compartments. The cytoplasmic concentration of free Mg2+ is buffered by binding to chelators (e.g. ATP), but also more importantly by storage of Mg2+ in intracellular compartments. The transport of Mg2+ between intracellular compartments may be a major part of regulating enzyme activity. The interaction of Mg2+ with proteins must also be considered for the transport of the ion across biological membranes.
In biological systems, only manganese (Mn2+) is readily capable of replacing Mg2+, but only in a limited set of circumstances. Mn2+ is very similar to Mg2+ in terms of its chemical properties, including inner and outer shell complexation. Mn2+ effectively binds ATP and allows hydrolysis of the energy molecule by most ATPases. Mn2+ can also replace Mg2+ as the activating ion for a number of Mg2+-dependent enzymes, although some enzyme
activity is usually lost. Sometimes such enzyme metal preferences vary among closely related species: for example, the reverse transcriptase enzyme of lentiviruses like HIV, SIV and FIV is typically dependent on Mg2+, whereas the analogous enzyme for other retroviruses prefers Mn2+.
An article investigating the structural basis of interactions between clinically relevant antibiotics and the 50S ribosome appeared in Nature in October 2001. High resolution x-ray crystallography established that these antibiotics only associate with the 23S rRNA of a ribosomal subunit, and no interactions are formed with a subunit's protein portion. The article stresses that the results show "the importance of putative Mg2+ ions for the binding of some drugs".
Metals In Biology
Perpared By Zahran Bin Zuheer (A128089)
For Prof. Yang Farina Abdul Aziz
METALS IN BIOLOGY
Metals will rarely be thought of when one talks about biology. However, if one was to look more deeply in the chemistry that happens in most organisms, one will see that within most biological organisms,metlas play an inportant role in some of the more known biological processes such as photosynthesis and even oxygen transportation.
As was stated before, the prcess of oxygen transportation involves the red blood cells which are known as hemoglobin. The active site in hemoglobin is in actuallity an iron atom. The iron atom, acts as the site where the oxygen is bonded to the hemoglobin cell forming oxyhemoglobin. This is then transported through the whole body to cope with the body’s oxygen needs.
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 require metals to carry out their functions. Thus, metalloproteins have many different functions in cells, such as enzymes, transport and storage proteins, and signal transduction proteins.
Iron(II), 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 hemegroup. 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 which is coordinated by the sulphur atoms of four cysteine residues forming an almost regular tetrahedron. Rubredoxins perform oneelectron 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.
Copper proteins have diverse roles in biological electron transport and oxygen transportation, processes that exploit the easy interconversion of Cu(I) and Cu(II). The biological role for copper commenced with the appearance of oxygen in earth's atmosphere. The protein hemocyanin is the oxygen carrier in most mollusks and some arthropods such as the horseshoe crab(Limulus polyphemus). Because hemocyanin is blue, these organisms have blue blood, not the red blood found in organisms that rely on hemoglobin for this purpose. Structurally related to hemocyanin are the laccases and tyrosinases. Instead of reversibly binding oxygen, these proteins hydroxylate substrates, illustrated by their role in the formation of lacquers.
The most important role of the molybdenum in living organisms is as a metal heteroatom at the active site in certain enzymes. In nitrogen fixation in certain bacteria, the nitrogenase enzyme, which is involved in the terminal step of reducing molecular nitrogen, usually contains molybdenum in the active site (though replacement of Mo with iron or vanadium is also known). The structure of the catalytic center of the enzyme is similar to that in iron-sulfur proteins: it incorporates a Fe4S3 and multiple MoFe3S3 clusters.
In 2008, evidence was reported that a scarcity of molybdenum in the Earth's early oceans was a limiting factor for nearly two billion years in the further evolution of eukaryotic life(which includes all plants and animals) as eukaryotes cannot fix nitrogen, and must therefore acquire most of their organic nitrogen from prokaryotic bacteria. The scarcity of molybdenum resulted from the relative lack of oxygen in the early ocean. However, once oxygen dissolved in seawater it helped dissolve molybdenum from minerals on the sea bottom, making it available to nitrogen-fixing bacteria and allowing them to provide more nitrogen for higher forms of life.
Although oxygen once promoted nitrogen fixation via making molybdenum available in water, it also directly poisons nitrogenase enzymes, so that historically, after oxygen arrived in large quantities in Earth's air and water, organisms which continued to fix nitrogen in aerobic conditions were required to isolate their nitrogen-fixing enzymes in heterocysts, or similar structures which protect them from too much oxygen.
The molybdenum cofactor (pictured) contains an organic complex called molybdopterin, which binds an oxidized molybdenum through adjacent sulfur (or occasionally selenium) atoms.
Though molybdenum forms compounds with various organic molecules, including carbohydrates and amino acids, it is transported throughout the human body as MoO42−.[50] At least 50 molybdenum-containing enzymes were known by 2002, mostly in bacteria, and their number is increasing with every year; those enzymes include aldehyde oxidase, sulfite oxidase and xanthine oxidase. In some animals, and in humans, the oxidation of xanthine to uric acid, a process of purine catabolism, is catalyzed by xanthine oxidase, a molybdenumcontaining enzyme. The activity of xanthine oxidase is directly proportional to the amount of molybdenum in the body. However, an extremely high concentration of molybdenum reverses the trend and can act as an inhibitor in both purine catabolism and other processes. Molybdenum concentrations also affect protein synthesis, metabolism and growth.[50]
In animals and plants these enzymes use molybdenum bound at the active site in a tricyclic molybdenum cofactor. All molybdenum-using enzymes so far identified in nature use this cofactor, save for the phylogenetically ancient molybdenum nitrogenases, which fix nitrogen in some bacteria and cyanobacteria.[53] Molybdenum enzymes in plants and animals catalyze the oxidation and sometimes reduction of certain small molecules, as part of the regulation of nitrogen, sulfur and carbon cycles.[54]
The human body contains about 0.07 mg of molybdenum per kilogram of weight.[55] It occurs in higher concentrations in the liver and kidneys and in lower concentrations in the vertebrae.[5] Molybdenum is also present within human tooth enamel and may help prevent its decay.[56]
The average daily intake of molybdenum varies between 0.12 and 0.24 mg, but it depends on the molybdenum content of the food.[57] Pork, lamb and beef liver each have approximately 1.5 parts per million of molybdenum. Other significant dietary sources include green beans, eggs, sunflower seeds, wheat flour, lentils, cucumbers and cereal grain.[6]Acute toxicity has not been seen in humans, and the toxicity depends strongly on the chemical state. Studies on rats show a median lethal dose (LD50) as low as 180 mg/kg for some Mo compounds.[58] Although human toxicity data is unavailable, animal studies have shown that chronic ingestion of more than 10 mg/day of molybdenum can cause diarrhea, growth retardation, infertility, low birth weight and gout; it can also affect the lungs, kidneys and liver.[57][59] Sodium tungstate is a competitive inhibitor of molybdenum. Dietary tungsten reduces the concentration of molybdenum in tissues.[5]
Dietary molybdenum deficiency from low soil concentration of molybdenum has been associated with increased rates of esophageal cancer in a geographical band from northern China to Iran.[60][61] Compared to the United States, which has a greater supply of molybdenum in the soil, people living in these areas have about 16 times greater risk foresophageal squamous cell carcinoma.[62]
Molybdenum deficiency has also been reported as a consequence of non-molybdenum supplemented total parenteral nutrition (complete intravenous feeding) for long periods of time.[citation
needed]
It results in high blood levels of sulfite and urate, in much the same way
as molybdenum cofactor deficiency. However, presumably since pure molybdenum deficiency from this mechanism is seen primarily in adults, the neurological consequences have not been as marked as for the congenital cofactor deficiency.
Copper is also a component of other proteins associated with the processing of oxygen. In cytochrome c oxidase, which is required for aerobic respiration, copper and iron cooperate in the reduction of oxygen. Copper is also found in many superoxide dismutases, proteins that detoxify superoxides, by converting it (by disproportionation) to oxygen and hydrogen peroxide: 2 HO2 → H2O2 + O2
Several copper proteins, such as the "blue copper proteins", do not interact directly with substrates, hence they are not enzymes. These proteins relay electrons by the process called electron transfer.[74]
Plastocyan is one of the family of blue copper proteins which are involved in electron transfer reactions. The copper binding site is described as a ‘distorted trigonal pyramidal’.[13] 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 picometers) than Cu-S2 (282 pm). The elongated Cu-S2 bonding destabilises the CuII form and increases the redox potential of the protein. The blue colour (597 nm peak absorption) is due to the Cu-S1 bond where Spπ to Cudx2-y2 charge transfer occurs.[14]
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.
Most well-nourished people in industrialized countries have 4 to 5 grams of iron in their bodies. Of this, about 2.5 g is contained in the hemoglobin needed to carry oxygen through the blood, and most of the rest (approximately 2 grams in adult men, and somewhat less in women of childbearing age) is contained in ferritin complexes that are present in all cells, but most common in bone marrow, liver, and spleen. The liver's stores of ferritin are the primary physiologic source of reserve iron in the body. The reserves of iron in adults in
industrialized countries tend to be lower in children and women of child-bearing age, than in men and in the elderly. Women who must use their stores to compensate for iron lost throughmenstruation, pregnancy or lactation, have lower body stores, which may consist of 500 mg or even less.
Of the body's total iron content, about 400 mg is devoted to cellular proteins that use iron for important cellular processes like storing oxygen (myoglobin), or performing energyproducing redox reactions (cytochromes). A relatively small amount (3-4 mg) circulates through the plasma, bound to transferrin. [5]. Because of its toxicity, free soluble iron (soluble ferrous ions Fe(II)) is kept in low concentration in the body.
Iron deficiency first attacks the storage iron in the body, and depletion of these stores is thought to be relatively non-symptomatic, although some vague and non-specific symptoms have been associated with it. Since so much iron is required for hemoglobin, iron deficiency anemia is the primary clinical manifestation of iron deficiency. Oxygen transport is so important to human life that severe anemia harms or kills people by depriving their organs of enough oxygen. Iron-deficient people will suffer or die from organ damage well before cells run out of the iron needed for intracellular processes like electron transport.
Macrophages of the reticuloendothelial system store iron as part of the process of breaking down and processing hemoglobin from engulfed red blood cells.
Iron is also stored as a pigment called hemosiderin in an apparently pathologic process. This molecule appears to be mainly the result of cell damage. It is often found engulfed bymacrophages that are scavenging regions of damage. It can also be found among people with iron overload due to frequent blood cell destruction and transfusions.
Organobromine compounds in a number of species of marine algae are generated by the action of a vanadium dependentbromoperoxidase. This is a haloperoxidase in algae which requires bromide and is an absolutely vanadium-dependent enzyme. Most organobromine compounds in the sea ultimately arise via the action of this vanadium bromoperoxidase.[49]
German
chemist
Martin
Henze
discovered squirts) in
vanadium 1911.[50][51] It
in is
the blood essential
cells (or coelomic cells)
of Ascidiacea (sea
to ascidians and tunicates, where it is stored in the highly acidified vacuoles of certain blood cell types, designated vanadocytes.Vanabins (vanadium binding proteins) have been identified in the cytoplasm of such cells. The concentration of vanadium in their blood is up to 10 million times higher than the concentration of vanadium in the seawater around them. The function of this vanadium concentration system, and these vanadium-containing proteins, is still unknown.
A vanadium nitrogenase is used by some nitrogen-fixing micro-organisms, such as Azotobacter. In this role vanadium replaces more common molybdenum or iron, and gives the nitrogenase slightly different properties.[52]
Several species of macrofungi, namely Amanita muscaria and related species, accumulate vanadium (up to 500 mg/kg in dry weight). Vanadium is present in the coordination complex, amavadin,[53] in fungal fruit-bodies. However, the biological importance of the accumulation process is unknown.[54][55] Toxin functions
or peroxidase enzyme functions have been suggested.
Rats and chickens are also known to require vanadium in very small amounts and deficiencies result in reduced growth and impairedreproduction.[56] Vanadium is a relatively controversial dietary supplement, primarily for increasing insulin sensitivity[57] and bodybuilding. Whether it works for the latter purpose has not been proven, and there is some evidence that athletes who take it are merely experiencing a placebo effect.[58] Vanadyl sulfate may improve glucose control in people with type 2 diabetes.[59][60][61][62][63] In addition, decavanadate and oxovanadates are species that potentially have many biological activities and that have been successfully used as tools in the comprehension of several biochemical processes.[64]
The process of photosynthesis also involves metals in its process. Chlorophyll, in leaves of the plants, which make up the 3 necessary parts of photosynthesis, the other two being carbon dioxide and light, actually has a magnesium atom as the center of its chemical structure. Its discovery in the early 1900’s is actually the first time that this particular element was found in a living tissue.
The chemistry of the Mg2+ ion, as applied to enzymes, uses this ion’s chemistry to fulfill a range of functions. Mg2+ interacts with substrates, enzymes and occasionally both (Mg2+ may form part of the active site). Mg2+ generally interacts with substrates through inner sphere coordination, stabilising anions or reactive intermediates, also including binding to ATP and activating the molecule to nucleophilic attack. When interacting with enzymes and other proteins Mg2+ may bind using inner or outer sphere coordination, to either alter the conformation of the enzyme or take part in the chemistry of the catalytic reaction. In either case, because Mg2+ is only rarely fully dehydrated during ligand binding, it may be a water molecule associated with the Mg2+ that is important rather than the ion itself. The Lewis acidity of Mg2+ (pKa 11.4) is used to allow both hydrolysis and condensation reactions (most commonly phosphate ester hydrolysis and phosphoryl transfer) that would otherwise require pH values greatly removed from physiological values.
ATP (adenosine triphosphate), the main source of energy in cells, must be bound to a magnesium ion in order to be biologically active. What is called ATP is often actually MgATP.
Nucleic acids have an important range of interactions with Mg2+. The binding of Mg2+ to DNA and RNA stabilises structure; this can be observed in the increased melting temperature (Tm) of double-stranded DNA in the presence of Mg2+. Additionally, ribosomes contain large amounts of Mg2+ and the stabilisation provided is essential to the complexation of this ribo-protein. A large number of enzymes involved in the biochemistry of nucleic acids bind Mg2+ for activity, using the ion for both activation and catalysis. Finally, the autocatalysis of many ribozymes (enzymes containing only RNA) is Mg2+ dependent (e.g. the yeast mitochondrial group II self splicing introns).
Magnesium ions can be critical in maintaining the positional integrity of closely clustered phosphate groups. These clusters appear in numerous and distinct parts of the cell nucleus and cytoplasm. For instance hexahydrated Mg2+ ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes.
Biological cell membranes and cell walls are polyanionic surfaces. This has important implications for the transport of ions, particularly because it has been shown that different membranes preferentially bind different ions. Both Mg2+ and Ca2+ regularly stabilise membranes by the cross-linking of carboxylated and phosphorylated head groups of lipids. However, the envelope membrane of E. coli has also been shown to bind Na+, K+, Mn2+ and Fe3+. The transport of ions is dependent on both the concentration gradient of the ion and the electric potential (ΔΨ) across the membrane, which will be affected by the charge on the membrane surface. For example, the specific binding of Mg2+ to the chloroplast envelope has been implicated in a loss of photosynthetic efficiency by the blockage of K+ uptake and the subsequent acidification of the chloroplast stroma.
The Mg2+ ion tends to bind only weakly to proteins (Ka ≤ 105[28]) and this can be exploited by the cell to switch enzymatic activity on and off by changes in the local concentration of Mg2+. Although the concentration of free cytoplasmic Mg2+ is on the order of 1 mmol/L, the total Mg2+ content of animal cells is 30 mmol/L[36] and in plants the content of leaf endodermal cells has been measured at values as high as 100 mmol/L (Stelzer et al., 1990), much of which is buffered in storage compartments. The cytoplasmic concentration of free Mg2+ is buffered by binding to chelators (e.g. ATP), but also more importantly by storage of Mg2+ in intracellular compartments. The transport of Mg2+ between intracellular compartments may be a major part of regulating enzyme activity. The interaction of Mg2+ with proteins must also be considered for the transport of the ion across biological membranes.
In biological systems, only manganese (Mn2+) is readily capable of replacing Mg2+, but only in a limited set of circumstances. Mn2+ is very similar to Mg2+ in terms of its chemical properties, including inner and outer shell complexation. Mn2+ effectively binds ATP and allows hydrolysis of the energy molecule by most ATPases. Mn2+ can also replace Mg2+ as the activating ion for a number of Mg2+-dependent enzymes, although some enzyme
activity is usually lost. Sometimes such enzyme metal preferences vary among closely related species: for example, the reverse transcriptase enzyme of lentiviruses like HIV, SIV and FIV is typically dependent on Mg2+, whereas the analogous enzyme for other retroviruses prefers Mn2+.
An article investigating the structural basis of interactions between clinically relevant antibiotics and the 50S ribosome appeared in Nature in October 2001. High resolution x-ray crystallography established that these antibiotics only associate with the 23S rRNA of a ribosomal subunit, and no interactions are formed with a subunit's protein portion. The article stresses that the results show "the importance of putative Mg2+ ions for the binding of some drugs".
