Csir QN Papers

Prepared by V.
Aditya vardhan
adichemadi(at)gmail.com
WARANGAL
This is updated on 22nd Nov, 2009 and going to be updated frequently. For recent updates and other parts, visit
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BIOINORGANIC CHEMISTRY Note: Questions solved from csir and gate exams 41) Complexes of which of the following metals are used in the treatment of rheumatoid arthritis: 1. Gold 2. Ruthenium 3. Iron 4. Copper Explanation * Gold salts (containing Au(I)) like Auranofin, Sodium aurothiomalate, aurothioglucose are used to treat rheumatoid arthritis. Additional information
Some applications of metals in medicine * cis platin and budotitane are used in treatment of cancer. * Iron in the form of ferrous sulfate, ferrous gluconate are used in treatment of iron deficiency anemia. * Li+, in the form of Li2CO3, is used in the treatment of depression, hypertension. * Sb(III) salts are used in eczema (inflammatory condition of skin). * Bi(III) salts (as Bismuth subsalicylate ) are used in gastric ulcer. * BaSO4 is used as contrast agent in radiography. * Gd3+ is used as contrast agent in NMR. * 99mTc (in Cardiolyte) is used in radio diagnostics. 99mTc is a metastable isotope of Technetium, an artificially made element. Its half life is 6hrs only and emits gamma rays. * Silver sulfadiazine is used to treat and prevent bacterial or fungal infections of the skin. * Selenium sulfide used to treat seborrheic dermatitis and Tinea versicolor. * MoS42- (tetrathiomolybdate) is used as anti copper agent in Wilsons disease (excess of copper accumulation in liver - a genetic disorder). It is also used as an antitumor agent. Inorganic elements and their biological functions Bulk metals - Na, K, Mg, Ca Trace metals - Zn, Fe, Co, Ni, Cu, Mo, V - metals with low conc. are used for biocatalysis. * Na+,K+: As electrolytes, maintain the concentration gradient (osmotic balance). Helps in active and passive transport. Charge carriers. 2+ * Mg : Present in chlorophyll. In energy production (ATP --->ADP); Activation of enzymes. Information carrier; Present in endo and exo skeletons. 2+ * Ca : Charge carrier. In muscle and nerve functions - cell signalling. It acts as second messenger and sen-
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TP V. :// AD W IT W Y W A .A VA DI R CH D EM HA AD N I.C O M
Prepared by V. Aditya vardhan
WARANGAL
Bioactivity and accompanying metals * Electron carriers Fe : cytochrome, iron-sulfur protein; Cu : blue copper protein. * Metal storage compound
* Oxygen transportation agent
* Photosynthesis
* Hydrolase
* Oxidoreductase
* Isomerase
Fe: aconitase. Co: vitamin B12 coenzyme. % of Elements in Earth Crust and in Human Body
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Mg: chlorophyll in PSI Mn: part of OEC in PSII Zn: carboxypeptidase. Mg: aminopeptidase. Fe: oxygenase, hydrogenase. Fe, Mo: nitrogenase.
tinel at synapse. Present in teeth as Ca5(PO4)3(OH) (hydroxylapatite), and CaCO3, Present in endo and exo skeletons; In activation of enzymes; In blood coagulation. IV/V * V , MoIV/VI, WIV/VI, MnII/III/IV, FeII/III, NiI/II/III, CuI/II: electron transfer * Fe and Cu: Transport and storage of dioxygen. Fe3O4 is used to store iron, and, as it is magnetic, is used by magnetotactic bacteria to sense the direction of the Earths magnetic field. * Co: Cobalamine, e.g. Vitamin-B12 * Mn: In photosynthesis, generation of dioxygen by splitting water. Mn is part of OEC (Oxygen Evolving Complex) in PS II. * Mo, Fe & V: Conversion of N2 to ammonia (nitrogen fixation). * Zn2+: Enzymes, zincfinger proteins (genetic transcription), stabilization of proteins. * Si(IV) Bones. * P5+: Hydroxylapatite, ATP, cell membrane, DNA. * Se(II): Selenocysteine * F-: As fluorapatite (Ca5(PO4)3F) in teeth. * Cl : Most important free anion, besides HCO3* I: functioning of hormones of the thyroid, in radiation therapy. 2+ * Ni : Hydrogenase and hydrolases (urease).
Fe : ferritin (related is transferrin which transport iron) Zn : metallothionein. Fe: hemoglobin (related is myoglobin which stores O2) Cu: hemocyanin.

Earth crust Element % O 47 Si 28 Al 7.9 Fe 4.5 Ca 3.5 Na 2.5 K 2.5 Mg 2.2
Human body Element % O 63 C 25.5 H 9.5 N 1.4 Ca 0.31 P 0.22 K 0.08 S 0.06
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Additional questions: 41.1) Give the structure, hybridization and magnetic moment of cis-platin? Write its action on cancer cells.
Note: chlorido is very recent IUPAC usage instead of chloro. * Pt (Z=78). Belongs to Nickel group. with e.c - [Xe] 4f14 5d8 6s2 * For Pt2+ -- [Xe] 4f14 5d8 . * Hybridization of Pt2+ is dsp2 . It is a square planar and low spin complex with zero magnetic moment. The crystal field splitting of square planar complexes is shown below.
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Ans:-
cis-Diamminedichloridoplatinum(II)
More stuff - with brief explanation * Superoxide dismutase, present in the cytosol, is a Cu-Zn containing enzyme catalyzing the disproportionation of O2- (superoxide) to O22- (peroxide) and H2O. * Hemocyanins are respiratory metalloproteins containing two copper atoms that reversibly bind a single oxygen molecule (O2). * In terms of abundance in the human body, zinc is the most important trace element after iron. Zinc is present in i) carbonic anhydrase, an enzyme, which converts HCO3- to CO2. ii) zinc finger proteins which recognize specific DNA sequences and are involved in gene function. iii) Liver Alcohol DeHydrogenase (LADH), which facilitate the inter conversion between alcohols and aldehydes (or ketones). * Normal nitrogenase enzymes contain Mo and Fe, but less common forms with vanadium are also known. Nitrogenase enzyme catalyses conversion of N2 to ammonia. * Vitamin B-12 contains Co(III). There is a corrin ring system in it. (Can you mention the difference between heme and corrin ring systems?) * Among the metals present in human body, the most abundant is Calcium. * Be, Cd, Hg, Tl and Pb are toxic elements. These elements have strong complexing ability and an especially strong affinity for sulfur. They may displace essential elements such as Ca and Fe, and may also disrupt protein structure by breaking S-S bridges. Once attached to suitable ligands they are hard to displace. Chelation therapy is used in treatment for heavy metal poisoning. It uses chelating ligands like EDTA that bind very strongly with toxic elements in complexed form and remove them.
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41.2) Why are d-metals such as Mn, Fe, Co, and Cu are present in redox enzymes in preference to Zn, Ga, and Ca? Ans:- Mn, Fe, Co, Cu occur naturally in redox enzymes because they can have at least two stable oxidation states. Redox reactions involve the cyclic oxidation and reduction of the metal ion. The other metals i.e., Zn, Ga, Ca, have only one stable oxidation state, and hence cannot be oxidized or reduced at physiological potentials. However Zn and Ca are also present in biological systems to carry out other functions. 41.3) What are ferritin, apoferritin and transferrin? Ans:- Ferritin is a globular protein complex consisting of 24 protein subunits and is the main intracellular iron storage protein in both prokaryotes and eukaryotes. It has the shape of a hollow sphere. Inside the sphere, iron is stored in the Fe(III) oxidation state. It is incorporated in the mineral ferrihydrite, [FeO(OH)]8[FeO(H2PO4)], which is attached to the inner wall of the sphere. Whenever required by the body, iron is reduced and released as hydrated Fe(II). Ferritin that is not combined with iron is called apoferritin. Transferrin is a glycoprotein present in blood plasma that binds Fe(III) very tightly but reversibly. Affinity to iron decreases with decrease in pH. It helps in transport of iron. 41.4) What is the function of Mn in photosynthesis? Ans:- Mn is present in Oxygen Evolving Complex (OEC) of photosystem-II. It helps in generation of dioxygen by oxidising water molecule.The OEC is a cluster compound containing four Mn ions (probably two in Mn(II) and Mn(IV) states). These help in electron tranfer reactions.
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(Glu)O
O
Action: Upon administration to the cancer patient, the chloride ligands are displaced by water and thus aqua platinum complexes are formed in cells, which bind and cause crosslinking of DNA---- ultimately triggers apoptosis - programmed cell death.
N(His)
(His)N Mn
Mn
O
(Glu)O H2O
H2O
O
Asp OH2 O(Glu) Oxygen Evolving Complex (OEC)
Ca
O
Mn H2O
Mn O OH
H2O
Asp
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41.5) What is the active site in carboxy peptidase? Mention its role? Ans:- The active site in carboxy peptidase contains tetrahedrally coordinated Zn2+. It is coordinated to two histidine residues, one glutamate residue and one water molecule.
OH2 Zn His(N) His(N)
2+
O(Glu)
Do you know the Edman degradation (in the laboratory) is a method for removing the N terminal amino acid? If you dont, just remember. 41.6) What is the active site in carboxy anhydrase? Mention its role? Ans:- The active site in carboxy anhydrase (carbonic anhydrase) contains tetrahedrally coordinated Zn2+. It is coordinated to three histidine residues and one water molecule.
OH 2 Zn
Function: It catalyzes the conversion of carbondioxide to bicarbonate.

Carbonic anhydrase CO 2 + H2O H + HCO 3
+ -
Mechanism: Step 1: Deprotonation of coordinated water molecule. This is crucial step. The zinc bound water is more acidic than free H2O and loses proton easily. Step 2: Thus formed zinc bound hydroxyl group carries out nucleophilic attack on CO2 to get (His)3Zn-OCO2H complex. (IT IS A NUCLEOPHILIC ADDITION ON CO2) Step 3: Displacement of -OCO2H by water molecule.
H+
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41.6) What is the active site in Liver Alcohol Dehydrogenase (LADH)? Mention its role? Ans:- The active site in carboxy anhydrase (carbonic anhydrase) contains tetrahedrally coordinated Zn2+. It is coordinated to two cysteine residues, one histidine residue and one water molecule.
2+
Funtion: It is a hydrolase enzyme. It removes C-terminal aminoacid from a protein. This process is repeated until all the amino acids are removed from C-end. Thus this enzyme helps in degradation of peptides in biological systems. Mechanism: i) Zn2+ activates water molecule for nucleophilic attack ii) H2O is polarized by a nucleophile (base) iii) polarization of carbonyl bond which is to be cleaved.
His(N)
(N)His
His(N)
(His)3Zn -OH2
-
2+
(His)3Zn -OH
-HCO 3
CO2
H2O
(His)3Zn -OCO2H
adichemadi(at)gmail.com OH 2 Zn Cys(S) Cys(S)

2+
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(N)His
Function: It catalyses the oxidation of primary and secondary alcohols to the corresponding aldehydes or ketones by the transfer of a hydride anion to NAD+ with release of a proton.
OH R H R
1
NAD
LADH R
O R
1
NADH
a) Tetrahedral coordination is one of several environments observed for both Co2+ and Zn2+. b) Tetrahedral Co2+ and Zn2+ are both diamagnetic. c) The ionic radius of Co2+ is significantly smaller than that of Zn2+. d) The visible spectra of complexes of Co2+ are similar to those of related complexes of Zn2+. Ans:- a. * The spectral behaviour of Co2+ (d7, paramagnetic) is different from Zn2+ (d10, diamagnetic, colorless, no visible spectra). This difference is used in in vitro studies; * the ionic radii of Co2+ and Zn2+ are almost same; * Co2+ can tolerate similar coordination environments to Zn2+; * it is often possible to replace Zn2+ in a protein by Co2+ without greatly disturbing the protein conformation. 41.8) Nature has chosen Zn(II) ion at the active site of many hydrolytic enzymes because (a) Zn (II) is a poor Lewis acid. (b) Zn (II) does not have chemically accessible redox states. (c) Zn (II) forms both four and higher coordination complexes (d) Zn (II) forms weak complexes with oxygen donor ligands. Ans:- The unique features of zinc are * It exists only in +2 state. It has no chemically accessible redox states i.e., redox inactive and hence no redox side reactions. * There are no ligand field stabilization effects due to its d10 configuration. Hence there are no ligand field constaints over the geometry. Its geometry and coordination number are only dictated by ligands and the charge. * Usually zinc adopts usually tetrahedral geometry in biocomplexes (some square pyramidal complexes are also reported). * It is a good lewis acid next to copper. * It is a borderline hard acid and can bind to oxygen (Asp, Gu, H2O), nitrogen (His) and sulfur (Cys). 41.8) Dioxygens reduction potential is +0.816 mV at pH = 7 and hence is a good oxidizing agent. Yet it does not react with organic molecules under normal conditions. Explain. Ans:- Dioxygen in the ground state exists in triplet state, whereas organic molecules are mostly in singlet state. Hence dioxygen is kinetically inert towards organics. But it readily reacts with metals irreversibly. (That is why iron in hemoglobin is to be protected in the hydrophobic environment of globin.)
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41.7) Studies of Zn(II)-containing proteins often make use of Co(II)-for-Zn(II) substitution. Which statement is correct?
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41.9) What is Calmodulin (CaM)? Mention its role? Ans:- Calmodulin (CALcium MODULated proteIN) is a calcium binding protein present in all eukaryotic cells. It can bind to and regulate a multitude of different protein targets, thereby affecting many different cellular functions such as inflammation, metabolism, apoptosis, muscle contraction, intracellular movement, short-term and long-term memory, nerve growth and the immune response. 41.10) What are porphyrins? Draw the structures of different types of porphyrins in biological systems. Ans:- Porphyrins are the substituted porphins which are heterocyclic macrocyclics containing 4 modified pyrrole rings interconnected at their alpha carbons via methine(=CH-) bridges. The simplest porphin found in Hemoglobin is called porphyrin. The porphin in chlorophyll is called chlorin. In vitamin B12, the two of the pyrrole rings are directly connected to each other. This type of porphin is called corrin. Porphyrin is a highly conjugated system and deeply colored. It is aromatic containing 26 -electrons, a Huckel number. .
Note: Actually above rings are substituted at various places by different substituents.
41.11) What are ionophores? Mention their role in biology. Ans:- An ionophore is a lipid soluble macrocyclic molecule, which transport ions (especially hard cations) across the lipid bilayer of the cell membrane. Ionophores are involved in passive transport. There are two types of ionophores as follows; * Carrier ionophores which bind to a particular ion and facilitates its transport through the lipid membrane. It shields the charge on ion from the surroundings and forms a lipophilic shell around the ions. * Channel forming ionophores, which form a hydrophilic pore (or channel) in a membrane, allowing ions to pass through it. Ionophores are charge and size selective. They usually coordinate through O and N. Chelation plays major role in stabilizing the complex. Selectivity depends on number of coordination bonds and confirmation of ionophore. These are used to used to increase the permeability of biological membranes to certain ions and also act as antibiotics. Ionophores disrupt transmembrane ion concentration gradients, required for the proper functioning and survival of microorganisms, and thus have antibiotic properties.
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N NH N NH N NH NH N NH N N N
Porphyrin e.g. Heme
Chlorin e.g. Chlorophyll
Corrin e.g. Vitamin B12
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Examples of ionophores with the ions upon which they act. Valinomycin (K+) Salinomycin (K+) Gramicidin A (H+, Na+, K+) ---- It is a transmembrane channel forming ionophore. Nonactin (NH4+) Ionomycin (Ca2+) 2,4-Dinitrophenol (H+) Monensin (H+, Na+) ----- used in cattle feed * Crown ethers are the laboratory analogues of ionophores. 41.12) Why Gadolinium salts are used as MRI agents? * A good MRI agent should have following charactersitics: 1) High magnetic moment; 2) Long electron-spin relaxation time; 3). Low toxicity; * Gd3+ salts like [Gd(dtpa)(H2O)]2-(gadopentetate dimeglumine) and [Gd(dota)(H2O)](gadoterate meglumine) fit this for the purpose.
Practice questions 1) Identify one significant role in biological processes for the elements Fe, Mo, Mn and Cu. 2) In biological systems, the metal ion involved in the dioxygen transport besides Fe is a) Co b) Zn c) Mg d) Cu
3) In photosynthesis, the predominant metal present in the reaction centre of photosystem II is (a) Zn (b) Cu (c) Mn (d) Fe 4) Zn in carbonic anhydrase is coordinated by three histidine and one water molecule. The reaction of CO2 with this enzyme is an example of (a) electrophilic addition (b) electron transfer (c) nucleophilic addition (d) electrophilic substitution. 5) The metals involved in nitrogenase are (a) Fe and Mg (b) Mo and K
6) The transition metal present in vitamin B12 is_______
8) Match the following 1) Li+ 2) Bi3+ 3) Sb3+ 4) Fe2+
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7) The trivalent ion of lanthanoid element which is used as NMR contrasting agent is 1) Gadolinium 2) Technetium 3) Cerium 4) Lutetium
9) The enzyme which removes C-terminal amino acid from a peptide is 1) Carbonic anhydrase 2) Carboxy peptidase 3) Zymase
(c) Mo and Fe (d) Fe and K A) Ulcer treatment B) Eczema C) Anemia D) Depression 4) All
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10) Which of the following metal is stored by metallothionein in biological systems? 1) Fe 2) Cu 3) Zn 4) Co 11) The metals present in superoxide dismutase are a) Zn & Fe 2) Cu & Fe 3) Mo & Cu
4) Cu & Zn
12) In human body, the most abundant nonmetal is _____ and most abundant metal is _____. 13) The copper containing non heme respiratory protein is 1) Cytochrome-c 2) Hemerythrin 3) Hemocyanin 14) The oxidation state of iron stored in ferritin is 1) +2 2) +1 3) +3 4) 0
4) Myoglobin
15) The enzyme which catalyzes the conversion of carbondioxide to bicarbonate is 1) Carboxy peptidase 2) Superoxide dismutase 3) Carboxy anhydrase 4) Hydrogenase
16) The number of methine bridges present in porphyrin is _______ and in corrin is _____ . 17) The ionophore used in the cattle feed to improve the permeability of Na+ and H+ ions is 1) Crown ethers 2) Monesin 3) Ionomycin 4) Nonactin 18) Match the following A) Silver sulfadiazine B) Selenium sulfide C) tetrathiomolybdate D) Cardiolyte
19) The function of Na+ and K+ in biological systems is 1) To maintain osmotic balance in the cells 2) Help in active & passive transport 3) As charge carriers 4) All 20) Fluoride is present in the teeth in the form of 1) CaF2 2) Na3AlF6 3) Ca5(PO4)3F
21) Which of the following is a channel forming ionophore? 1) Valinomycin 2) Salinomycin 3) Gramicidin
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22) The porphin system in chlorophyll is called as 1) porphyrin 2) chlorin
23) The metal present in both superoxide dismutase and hemocyanin is a) Zn b) Fe c) Cu d) Ni 24) The metal ion present in urease is____ . 25) The ionophore valinomycin is highly selective for: a) K+ b) Na+ c) Mg2+
1) Anti copper agent 2) Skin fungal infections 3) Radiodiagnosis 4) Seborrheic dermatitis 4) CaF2.CaCO3 4) All 3) corrin 4) heme d) Ca2+
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Hint: The stability constant of complex formed by valinomycin with K+ is 106, whereas that with Na+ is 10. 42) Non-heme iron-sulfur proteins are involved in: 1. Electron transfer. 2. Proton transfer. 3. Both electron and proton transfer 4. Oxygen transfer. Explanation * Iron-sulfur proteins are proteins characterized by the presence of iron-sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. E.g., Ferredoxins, as well as NADH dehydrogenase, hydrogenases, nitrogenase etc., * Iron-sulfur clusters are best known for their role in the oxidation-reduction reactions of mitochondrial electron transport. * Additionally some Fe-S proteins regulate gene expression. * Fe-S proteins are vulnerable to attack by biogenic nitric oxide. In most iron-sulfur proteins, the clusters function as electron-transfer groups. Additional information: 1) Ferredoxins: are small proteins containing iron and sulfur atoms organized as iron-sulfur clusters. These biological "capacitors" can accept or discharge electrons, the effect being change in the oxidation states (+2 or +3) of the iron atoms. Thus ferredoxin acts as electron transfer agents in biological redox reactions. The following diagram illustrates the redox scheme between low-potential and high-potential (HiPIP) ferredoxins containing Fe4S4clusters. The formal oxidation numbers of the iron ions can be [2Fe3+, 2Fe2+] or [1Fe3+, 3Fe2+] in low-potential ferredoxins. The oxidation numbers of the iron ions in high-potential ferredoxins can be [3Fe3+, 1Fe2+] or [2Fe3+, 2Fe2+]
S S S S
Fe
S Fe S
Following is Fe2S2 type of ferredoxin.

Cys
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Note: High potential iron-sulfur proteins (HiPIPs) form a unique family of Fe4S4 ferredoxins that function in anaerobic electron transport chains. * Aconitase hydratase contains Fe4S4 cluster in active form and Fe3S4 cluster in inactive form. * Rubredoxin is considered as another iron-sulfur protein which does not contain inorganic sulfide. It is also an electron transport agent.
Fe
S
Fe
Fe
1-
+e-e-
Fe
2-
+e-e-
Fe
3-
S Fe
S Fe
Fe
Fe
Fe
Cys
Fe S Cys
S S
Fe S Cys
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Hemoglobin and Myoglobin * Hemoglobin(Hb) and myoglobin(Mb) are the heme containing metalloproteins (Note: iron porphyrin system is called heme). Both of them contain Fe(II) ion. Hemoglobin is present in RBC and helps in transport of dioxygen from lungs to tissues. Whereas, myoglobin stores dioxygen and is present in muscles. * Hb contains four heme units and four globular protein sub-units whereas Mb contains only one heme unit surrounded by a globular protein.
* Globin part prevents irreversible oxidation of Fe(II) ion by providing hydrophobic environment. It enhances the selectivity for O2 binding. In hemoglobin, the tetramer allows for cooperativity which makes it more efficient in binding to dioxygen. * In deoxy-hemoglobin, four of the coordinated sites of iron are occupied by nitrogens of porphyrin ring. The fifth site is occupied by Histidine residue (called proximal histidine) of globin. The sixth position is occupied by weakly bonded water molecule. Deoxy-hemoglobin is said to be in T-state (tense). Another histidine group (distal), on the opposite side of the first histidine group, is situated near the iron and assists the binding of dioxygen in end on bent confirmation (This particular bent confirmation discourages the binding of CO to heme iron. Without this bent requirement, CO may have even more affinity with the iron. CO binds to hemoglobin 200X stronger than dioxygen but binds 20,000X stronger with unprotected heme).
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N N H
distal histidine
CH3
H3C N N
Fe
N H3C O OC-H2 C-H2 C
N H
-
2+
N CH3
N
CH2 -CH2 -COO
* Hb coordinated to dioxygen is called oxy-hemoglobin. It is also referred to as R-state (relaxed). In oxy-hemoglobin the sixth coordinated position of iron is occupied by dioxygen in end on bent geometry. * In deoxy-Hb, the porphyring ring is dome shaped. Fe(II) is in high spin state and is paramagnetic. It is bigger in size (0.78 Ao) and situated above the plane of the porphyring ring. * In oxy-Hb, the iron is in low spin state and diamagnetic. It is smaller in size (0.61 Ao) and can fit into the cavity of porphyrin ring (which now becomes planar). Now Fe(II) can move into the cavity of porphyrin ring and drags the proximal histidine which inturn triggers the confirmational changes in other globin subunits and opening of other heme sites. As a result, enhances the binding capacity of other heme irons (cooperativity through allostery).
O OC-H 2 C-H 2 C
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* There are two theories to explain the nature of Fe in oxy-Hb or oxy-Mb. Pauling model: Suggests presence of low spin Fe(II) and singlet O2. Both are diamagnetic. Weiss model: Suggests presence of Fe(III) and superoxide radical anion(O2-). Both are paramagnetic. But strong paramagnetic coupling results in diamagnetic nature. The O-O
proximal histidine
N N N H N H
H-bond
CH3
CH3
H3C
O
N
H3C
H3C
Fe
II
CH3
FeIII
N
CH 2 -CH 2 -COO
O OC-H 2 C-H 2 C
H3C
CH3
CH 2 -CH 2 -COO
N H
N H
Desoxy Hb Domed porphyrin High spin Fe(II) - out of ring
Oxy Hb Planar porphyrin Fe(III) - still high spin - into the ring Bent peroxy oxygen
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CYTOCHROMES * Cytochromes are, membrane-bound hemoproteins that contain 4 heme groups as cofactors and carry out electron transport. Most of them contain iron (either in Fe(II) or Fe(III) oxidation states) at their active site. They are found in the mitochondrial inner membrane and endoplasmic reticulum of eukaryotes, in the chloroplasts of plants, in photosynthetic microorganisms, and in bacteria. * Cytochromes are classified based on heme type or heme iron coordination. 1) Cytochrome-a contains heme-a 2) Cytochrome-b contains heme-b 3) Cytochrome-c contains heme-c * In cytochromes, the iron is hexacoordinated. The four coordination sites are occupied by four nitrogens on pyrrole rings of heme group and remaining are occupied by usually Histidine, Cysteine residues. * Depending upon the ligand, the redox potential of a given cytochrome can be tailored to meet specific need in electron transfer schemes. The potentials are such that the electron flow is always from cyt-b ----> cyt-c ----> cyt-a ----> O2 * In the mitochondrial electron-transfer chain, cytochrome-c accepts an electron from cytochrome-c1 and then transfersit to cytochrome c oxidase. Ultimately, the electron is used in the four-electron reduction of O2 * Only cytochrome-a has the ability to bind to O2 and reduce it. The CN- ion can bind strongly to the sixth coordination site and stabilize Fe(III) in cytochrome-a. This makes cyt-a to stop
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Mb - Hyperbolic curve
stretching frequency is1105 cm-1 as obtained in resonance raman spectroscopy is consistent with the fact that O2 is in superoxide form. This is more accurate and modern explanation. * Bisphosphoglycerate (BPG) reduces the affinity of Hb with oxygen. It binds at the centre of cavity between two beta-Hb units and stabilizes the T-state. It is observed that at high altitudes (on mountains), the amount of BPG increases in the blood. This wont affect the affinity of Hb with oxygen in lungs where the pO2 is very high but decreases the affinity in tissues and helps in release of dioxygen by stabilising the T-state of Hb. * Bohr effect: The affinity of Hemoglobin with dioxygen decreases with decrease in the pH of blood. Hence oxygen is released more efficiently in the tissues where CO2 concentration is high. The response of hemoglobin to changes in pH is called the Bohr effect. * The percent saturation with O2 curve of Hb against pO2 is sigmoidal whereas that of Mb is hyperbolic. This shows greater affinity of Mb with dioxygen even at low pO2 values. * Deoxyhemoglobin is the form of hemoglobin without the bound oxygen.The oxyhemoglobin has significantly lower absorption (660 nm) than deoxyhemoglobin (940 nm). This difference is used for measurement of the amount of oxygen in patient's blood by pulse oximeter.
% saturation with O2
Hb - Sigmoidal curve
pO2
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functioning in electron transfer reactions. CYTOCHROME-C OXIDASE * Cytochrome-c oxidase (not cytochrome-c) is the major respiratory protein of animal and plant mitochondria. It catalyzes the oxidation of Fe(II) of cytochrome-c, and the reduction of dioxygen to water by supplying four electrons. It contains two hemes (with two Fe3+) and three copper atoms, arranged in three centers. CYTOCHROME P450 * Cytochrome P450 oxidases constitute a super family of monooxygenase cytochromes. * They are so named for the characteristic Soret peak at wavelengths near 450 nm when the heme iron is reduced (with sodium dithionite - Na2S2O4) and complexed to carbon monoxide. * These enzymes are primarily involved in steroidogenesis and detoxification. * They oxidise the alkanes to alcohols. * Their reaction with dioxygen involve higher oxidation states of iron, such as Fe(IV). * In all monooxygenases, only one oxygen atom in dioxygen is transferred to the substrate while the other is converted into H2O.
P450 E.g.1) R 3CH + O2 + 2e- + 2H+ R 3C-OH + H2O
2)
Mechanism: * The active site has Fe centre which is switched between II, III and IV oxidation states. * In step-1, RH replaces H2O while the low spin Fe(III) is converted to high spin Fe(III). * The substrate RH is bonded by hydrophobic interaction into the protein pocket close to the active centre. * Only one oxygen atom is retained on the active site (step-5). Another is converted into water. * Overall two electrons are utilized.
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O P450 O H H Camphor OH H 5-Exo-hydroxy camphor
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H O N
step-1 RH N N Fe N N
3+
step-2 RH N N S(Cys) high spin eN N Fe

2+
Fe N
3+
RH
N N S(Cys)
S(Cys) low spin
S(Cys) Compound-I with Fe(IV)
Additional questions: 42.1) Give the structure of active site in Rubredoxin and mention its role? Ans:- Rubredoxin is a low molecular weight iron containing bacterial protein involved in electron transfer. Sometimes rubredoxins are classified as iron-sulfur proteins. However, in contrast to iron-sulfur proteins, rubredoxins do not contain inorganic sulfide. Rubredoxins active site contains an iron ion (either in II or III oxidation state) which is coordinated by the sulfurs of four cysteine residues forming an almost regular tetrahedron.
Cys S
Rubredoxins perform one-electron transfer processes. The central iron atom changes between the +2 and +3 oxidation states. In both oxidation states, the metal remains high spin, which helps to minimize structural changes. The oxidized state is reddish (due to a ligand metal charge transfer), while the reduced state is colourless (because the electron transition has an energy of the infrared level, which is imperceptible for the human eye). 42.2) Ferredoxin (Fd) is a sulfur-containing protein which undergoes redox reactions in a variety of microorganisms; Fdox+ + e- -------> Fdred , Eo = 0.439V at pH = 7.0. Will Fd generate hydrogen gas from hydronium ions dissolved in water if the standard potential
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RH N O RH N O
-
step-6
+H2O
-ROH
O2
-
step-3
RH N
O-
+2H
Fe
4+
Fe
3+
Fe
3+
-H2O
S(Cys)
S(Cys)
step-5
step-4
Fe
Cys
Active site of Rubredoxin
Cys
Cys
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for the reduction 2H+ + 2e- ---------> H2 is -0.421 at pH=7.0. Show the redox reaction and explain your answer. Ans:- L: 2H+(aq) + 2e- -----------> H2(g) ; Eo = -0.421V R: Fdox+ + e-----------> Fdred ; Eo = 0.439V Overall cell reaction Fdox+ + H2(g) + -----------> Fdred + 2H+(aq) Ecell = ER - EL = 0.439 - (-0.421)V = 0.86V ------- which is > 0 This means that rG < 0 (why? see the note). Hence reduction of Fdox+ is spontaneous and NOT the liberation of hydrogen. Therefore H2 gas is consumed, and not produced in this reaction. Note: 1) The electrode with low reduction potential is written on the Left hand side and that with high potential is written on the Right hand side of the galvanic cell. Left hand side half cell is considered as anode and oxidation occurs in this cell. Whereas, Right hand side half cell is the cathode where reduction occurs. 2) G = -nFE 42.3) In the following reaction ferredoxin-1 is the oxidised form of ferredoxin. State whether the following reaction is true or false?
nitrite reductase NO 2 - + ferredoxin-1 NH 3 + ferredoxin-2
Ans:- False. This is a reduction reaction. Hence only reduced form of ferredoxin can reduce NO2to ammonia as follows.
nitrite reductase NO 2- + ferredoxin-2 NH 3 + ferredoxin-1
42.4) What prevents synthetic (simple) iron porphyrins from functioning as O2 carriers? Ans:- In the naturally occuring porphyrins, like Hemoglobin, there is a globular protein around the heme groups. It prevents the irreversible oxidation of Fe(II) to Fe(III) and solvolysis of Fe(II)-O2 complex by providing hydrophobic environment around iron. It stops the formation of Fe-O2-Fe dimer. However in synthetic porphyrins, protein part is absent. As a result, Fe(II) is oxidized to Fe(III) and Fe-porphyrins easily dimerize to Fe-O2-Fe and then Fe-O-Fe (a -oxo dimer) and hence cannot function as oxygen carriers. 42.5) What is the active site in Rieske protein? Identify its role in bilological processes. Ans:- Rieske protein is an iron-sulfur protein (ISP) component of electron transfer chains like 1) cytochrome bc1 complex (found in mitochondria). 2) the cytochrome b6f complex (found in photosynthetic systems).
The active centre is Fe2S2 cluster in which one iron is coordinated by two cysteine residues and the other iron is coordinated by two histidine residues.
(Cys)S Fe (Cys)S S S Fe N(His) N(His)
HT
It is a 2Fe-2S protein. It was first discovered and isolated by John S. Rieske.
It is involved in electron transfer in respiration (in mitochondria) and photosynthesis (in
(reduced) (oxidised)
17
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chloroplasts). In mitochondria it accepts electron from Ubiquinol and transfers electron to heme iron in cytochrome-c. Whereas in Chloroplasts it accepts electron from Plastoquinol and transfers electron to heme iron in cytochrome-f. 42.6) Cytochrome C is a redox protein but myoglobin is an oxygen storage protein. Justify in 2-3 sentences. Ans:- In cytochrome C, the iron the six coordination sites are permanently occupied. It has fixed two axial ligands along with 4 pyrrole nitrogens from porphyrin ring. Hence it cannot store or carry dioxygen. It is an electron carrier.
But in Myoglobin or in Hemoglobin, the sixth coordinated site is occupied by losely bound water which can be replaced by dioxygen easily. Hence Mb and Hb can store and carry dioxygen respectively. (sometimes the iron in deoxy hemoglobin is said to be pentacoordinated only i.e., sixth coordinated site is vacant)
OH2 O O
42.7) Hemoglobin sometimes is called as dimer of dimers. Explain. Ans:- Hb contains two alpha and two beta subunits.
42.8) What are siderophores? Ans:- Siderophores are the multidentate anionic ligands released by microbes under extreme iron deficiency conditions. Under highly oxidising conditions, iron is oxidized to Fe3+ and forms insoluble Fe(OH)3. Hence not available to microbes. But microbes release siderophores to absorb them. These molecules chelate with Fe3+ and make insoluble Fe3+ into soluble form and thus help in absorption of iron. Citrate is a simple siderophore. Other e.g. Catecholates - like Enterobactin Hydroxamate - like Mycobactin Desferrichrome, Desferrioxamine B etc., Siderophores can fully satisfy the octahedral geometry requirements of iron without significant distortion and can bind flexibly.
HT
(S)Cys N N Fe N N (N)His Coordination pattern in Cytochrome C
N N N N Fe Fe N N N N (N)His (N)His Coordination pattern in Mb and Hb
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WARANGAL
Note:
1) Methanobactin is a siderophore for absorbing Cu metal. 2) In humans, iron is mobilized by transferrin.
42.8) What is the "Cooperative effect" in hemoglobin? Ans:- Coordination of one O2 leads to conformational changes in the protein chain leading to facilitated coordination of O2 by the other 3 sub-units in hemoglobin. 42.9) Explain why does carbon monoxide binds strongly to iron(II) porphyrin complexes but not iron(III) porphyrins. Compare the infrared frequency of CO in this complex to that of free CO. Ans:- The Fe(II)-CO bond is strong because there are strong d -p * backbonding interactions which strengthen the Fe-C bond. This is much less important for Fe(III)-CO because of higher positive charge on the metal. The IR frequency of free CO is higher than that of CO in a porphyrin complex because backbonding adds electron density to the * antibonding orbital of the CO bond, decreasing its strength. (cf. Question 51) 42.10) Why are all the oxygen carriers that contain iron and porphyrins are found inside the cells? Ans:- The inside cell environment is reducing and sustains Fe(II), whereas outside the cell the O2 concentration is high and hence the probability of the oxidation of Fe(II) ions to Fe(III) increases. 42.11) Write the steps involved in the formation of hematin, a -oxo dimer, from free heme. Ans:- Free heme in aqueous solutions is converted to hematin, a -oxo dimer when exposed to dioxygen. The steps involved are summarized below.
Fe
2+
Fe
2+
Fe
3+
HT
Fe
4+
Note: This -oxodiiron(III) moiety has a distinctive fingerprint that has made it easy to identify this motif in proteins regardless of the geometry, type and number of ligands. Magnetic susceptibility = 1.5 to 2.0 Bohr magnetons, indicating one unpaired electron. It is due to strong antiferromagnetic coupling of iron centres through oxygen. (Actually the value should be more) Asymmetric Fe-O stretching frequency at 730 - 880 cm-1
O2 Fe
2+
Binding of dioxygen molecule
+ O
Fe
3+
Fe
2+
Fe
3+
Formation of
peroxo complex
Fe
3+
Fe
4+
Fe
4+
Formation of ferryl complexes in which iron is in +4 formal oxidation state
Fe
2+
Fe
3+
O Fe
3+
Hematin formation
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42.12) What is the active site in Hemerythrin? Mention its role in marine invertebrates? Ans:- Hemerythrin is a iron containing NON HEME oligomeric protein which transports O2 in marine invertebrates. It is a respiratory protein. The monomer of hemerythrin is myohemerythrin, which is present in the muscles of marine invertebrates and stores dioxygen. (hemerythrin contains 8 subunits) Deoxy forms are colorless, whereas oxy forms are violet pink in color. Active site: The oxygen binding site is a binuclear iron centre. Deoxyhemerythrin contains two high-spin ferrous ions bridged by hydroxyl group The iron ions are coordinated to the protein through the carboxylate side chains of one glutamate, one aspartate, and five histidine amino acid residues. One iron is hexacoordinate and another is pentacoordinate.
The pentacoordinated Fe(II) binds to triplet dioxygen(3O2) and oxidized to Fe(III). Then the hydrogen on hydroxy group is transferred onto peroxide group. Now the second Fe(II) is also oxidized to Fe(III). In this process, an oxo bridge is formed between iron ions.
O O
2+
Unlike in hemoglobin, there is no cooperative effect observed in case of hemerythrin. Its affinity towards CO is less than with O2. 42.12) What is the active site in Hemocyanin? Mention its role? Ans:- Hemocyanin is respiratory protein containing two copper centres at the active site. It is a dioxygen carrier suspended in the hemolymph (blood) of most molluscs and arthropods. It contains NO HEME. The deoxy form contains Cu(I) ions and is colorless, whereas the oxy form contains Cu(II) and is blue in color.
HT
Histidine Histidine Histidine N N N N N Asp N O O Fe
2+
H O
Fe
2+
Asp
Histidine
Histidine
Fe
Fe
3+
O=O
Fe
2+
Fe
3+
Deoxy form Colorless
Oxy form Violet-pink
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In the deoxy form, each Cu(I) is coordinated to three histidine residues. Side-on bridging coordination occurs with dioxygen in its oxy form.
Histidine N N N Histidine N Histidine N Cu N
+
Histidine N N Cu N N Histidine
+
Histidine N O2 N O N Histidine N Histidine N Cu N

2+
Histidine N N Cu O N N Histidine
2+
N Histidine
N Histidine
* Cu(II) has d9 configuration. The unpaired electrons in both Cu(II) ions couple by a bonding interaction through the bridging peroxy ligand. Hence oxyHc is diamagnetic. Spectroscopic evidences of above oxyHemocyanin (oxyHc) structure; 1) Raman spectroscopy indicates symmetric binding and rules out mononuclear peroxo compound. 2) OxyHc is EPR silent indicating the absence of unpaired electrons. 42.13) How are the copper proteins classified? Describe their EPR behaviour? Ans:- In copper proteins, one or more copper ions are present as prosthetic groups. They are broadly divided into three types as follows: Type I : * Contain single copper atom, coordinated in distorted trigonal planar geometry to two histidine and a cysteine residue. A loosely bound methionine residue is also present at axial distant position. * These are called blue copper proteins or cupredoxins. They show beautiful intense blue color due to LMCT (Ligand to Metal Charge Transfer) at 600 nm. Charge transfer occurs between Cys-S to Cu(II). There is transfer of electron density from non bonding orbitals of sulfur atom of Cysteine to the empty d-orbitals. LMCT are Laporte permitted and hence show intense absorption. * Small hyperfine EPR coupling constant (5x10-4 cm-1). * They have relatively high reduction potentials (> 250 mV) * Function as electron transfer agent. * E.g. Plastocyanin ( helps in electron transfer in PSII to PSI) Type II: * Square planar geometry. Coordination through O or N. No coordination with S containing ligands. * His, Tyr and H2O are the ligands. There is no cysteine. * There are non blue copper proteins. Only normal d-d transitions are possible. As they are Laporte forbidden, the color is not intense. * Normal hyperfine EPR coupling constant (18x10-4 cm-1) comparable to regular copper coordination compounds. * Catalyse redox reactions. * E.g. Galactoseoxidase and superoxide dismutase
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Type III: * Contain two copper centres, each of which are coordinated by three histidine residues. * Intense blue color in oxidised form due to LMCT from O2- to Cu(II). * No EPR signal due to strong antiferromagnetic coupling between metal ions through the bridging ligand. The spins are paired up due to covalent overlapping of metal ions through the bridging ligand. * E.g. Hemocyanin, Tyrosinase. More examples: *Ceruloplasmin, which helps in absorption of iron, is a Cu protein containing 7 Cu centres representing types I, II and III. It is involved in the process of oxidizing Fe(II) to Fe(III) during the transfer of iron from transferritin to ferrritin. * Nitritereductase contains type II (substrate activation) and type I Cu centres (for e- transfer) Others: e.g.
CuA (binuclear copper centre) and CuB in cytochrome-c oxidase. Cuz centre found in nitrous-oxide reductase. It has 4 copper centres coordinated by 7 histidine residues and bridged by a sulfur atom. 41.14) Draw generally accepted structure of active site of the enzyme involved in nitrogen fixation. Indicate the site on which nitrogen first binds. Ans:- Nitrogenase catalyses the reduction of nitrogen to ammonia.
N 2 + 8e- + 8H + +16MgATP NH 3 + H 2 16MgADP + Pi
All the nitrogenases consists of two subunits i) M-cluster (FeMo cofactor) - containing Fe, S and Mo ii) P-cluster - containing Fe and S According to modern view, the M-cluster is involved in the reduction of dinitrogen to ammonia. The iron centres at the middle (shown in circles) are involved in binding of dinitrogen. (Note: These irons are just having three bonds and with open configuration)
S
The P-cluster contains cubane like [4Fe,4S] ferredoxins which are involved in the transfer of electrons to M-cluster. Note: The molybdenum, may be replaced by vanadium or iron in some organisms. 41.15) What is the action of Super Oxide Dismutase (SOD)? Ans:- Sequential additions of electrons to dioxygen during the action of oxygenase or oxidative phosphorylation produce harmfull species like superoxide, hydrogen peroxide. These species can be eliminated by super oxide dismutases (SODs) and catalases.
HT
S Fe Fe S O (Cys)S Fe S Fe S Fe S Mo O O S Fe Fe S N(His) S M-cluster
22
WARANGAL
SOD converts superoxide ion into oxygen and hydrogen peroxide. Catalases then convert hydrogen peroxide to oxygen and water.
O2
-
SOD Catalase
O 2 + H2O 2 O 2 + H2O
H2O 2
Usually SOD contains Cu-Zn active centre. The Cu and Zn atoms are connected through an imidazole ring(of histidine).
His His His Cu N N Asp Fe His His
During catalysis, the Cu binds to superoxide and cycles between the +1 and +2 oxidation states. Conversion of superoxide to oxygen occurs when the Cu is reduced from +2 to +1, and conversion of superoxide to hydrogen peroxide occurs when Cu is oxidized from +1 to +2.
SOD-Cu
2+ +
Practice questions 1) What is the role of globular protein in oxygen transport? cf. (42.4)
2) Which of the following is correct concerning the differences between hemoglobin and myoglobin? A) Hemoglobin is a monomeric protein and myoglobin is a tetrameric protein. B) Hemoglobin exhibits a hyperbolic O2 saturation curve while myoglobin exhibits a sigmoid shaped curve. C) Hemoglobin exhibits cooperative binding of O2 while myoglobin does not. D) Hemoglobin exhibits a higher degree of O2 saturation at all physiologically relevant partial pressures of O2 than does myoglobin. 3) The metal present in carbonic anhydrase is (a) Cobalt (b) Nickel (c) Zinc (d) Magnesium.
5) Which one of the following statements for hemoglobin is NOT correct? (A) The binding with O2 is weaker in comparison with myoglobin. (B) Iron is 5-coordinated. (C) Iron is coplanar with the porphyrin ring in the absence of oxygen. (D) The oxidation state of iron is +2. 6) When a reduced cytochrome transfers an electron from its Fe (II) to the bound O2,
HT
4) In biological systems, the metal ions involved in electron transport are (a) Na+ and K+ (b) Zn2+ and Mg2+ (c) Ca2+ and Mg2+ (c) Cu2+ and Fe3+
His
+ O2
SOD-Cu + O2
SOD-Cu + 2H + O2
SOD-Cu
2+
+ H2O 2
23
WARANGAL
(a) The bond order of O2 is reduced by one and O2 decreases. (b) A metal bound superoxide is formed and O2 decreases. (c) A metal bound superoxide is formed and O2 increases (d) The bond order of O2 is reduced by one and O2 increases 7) Match the following I P) Liver alcohol dehydrogenase Q) cytochrome C oxidase R) Hemocyanin S) Myoglobin
(a) P-6, Q-2 R-1, S-4 (c) P-3, Q-2, R-4, S-5
8) Match the following I P) Cytochrome C Q) Calmodulin R) Chlorophyll S) Alcohol dehydrogenase (a) P - I (b) P - II (c) P - III (d) P-V Q - II Q - III Q- IV Q- IV
9) Which statement is the correct description of hemerythrin? 1) A heme protein with one Fe centre at the active site.. 2) A metalloprotein containing two Fe centres at the active site. 3) A non-heme protein with one Fe centre at the active site. 4) A heme protein without Fe centre at the active site. 10) Match the following: P. Ferritin Q. Vitamin B12 R. Cytochromes S. Valinomycin
(a) P - VI Q - IV R-II S-I (b) P - I Q - III R-VI S - IV (c) P - III Q- V R - IV S- VI (d) P-VI Q-V R-I S - II Note: Vitamin B12 is an organometallic as there is a Co-C bond (metal-carbon bond). In the
HT
(b) P- 3, Q-2, R-1, S-4 (d) P-5, Q -6, R-1,S-2 II I) Zinc II) Potassium III) Magnesium IV) Calcium R -III R -IV R-I R - III S - IV S-I S- II S-I I. Electron transport II. Ionophore III. Oxygen transport IV. nitrogen fixation V. Organometallic enzyme VI. Iron storage.
II 1) Cu at the active site 2) Fe and Cu at the active site 3) Zn at the active site 4) Fe at the active site 5) Mo at the active site 6) Cu and Zn at the active site
24
WARANGAL
native form there is a methyl or methylene group attached to Cobalt. Whereas it is attached to a -CN group during isolation. Hence the name cyanocobalamine. 11) The iron containing respiratory protein without heme is _____. 12) The Cu-siderophore used in absorption of Cu by bacteria is 1) Methanobactin 2) Enterobactin 3) Mycobactin
4) Desferrioxamine
13) Inactive form of Aconitase hydratase, which catalyzes the stereospecific isomerization of citrate to isocitrate via cis-aconitase, contains 1) Fe4S4 cluster 2) Fe2S2 cluster 3) Fe3S4 cluster 4) Fe(S-Cys)4 cluster
15) Iron-sulfur proteins where one Fe atom is coordinated by two His residues are named: A) Poison iron-sulfur proteins B) Rieske iron-sulfur proteins C) Warburg iron-sulfur proteins D) Homo iron-sulfur proteins E) Cytochrome C iron-sulfur proteins 16) Which statement correctly describes the function of cytochromes P-450? 1) Cytochrome P-450 acts as monooxygenases and catalyses the insertion of O into a CH bond. 2) Cytochrome P-450 couples to cytochrome-c in the mitochondrial electron-transfer chain. 3) Cytochrome P-450 act as dioxygenases. 4) Cytochrome P-450 contains high-spin Fe(III); this directly binds O2 and acts as an O2 carrier. 17) Which statement about FeS proteins is INCORRECT? 1) A rubredoxin contains an FeS4 unit, each S coming from a Cysteine residue. 2) A [2Fe2S] ferredoxin contains six S donors, two of which are S2 ligands. 3) A [4Fe4S] ferredoxin contains a cubane core. 4) In a [4Fe4S] ferredoxin, four redox couples that make use of the four Fe centres are accessible in Nature. Note: In [2Fe-2S] iron-sulfur cluster, the 2 iron atoms are complexed to 2 inorganic sulfides and 4 sulfur atoms of cysteines from the protein. The incorrect statement is the 4th one. 18) Nitrogenase contains: A) an Fe-protein and an FeMo-protein that operate in conjunction with each other. B) an FeMo-protein in which the active site consists of a single [3FeMo-4S] cluster.
HT
14) Choose the incorrect statement about Types 1, 2 and 3 centres in copper proteins? a) Type 1 centre exhibits an intense LMCT band in the electronic spectrum. b) Ceruloplasmin contains all Types of copper centres. c) Type 3 centre contains two Cu centres which are antiferromagnetically coupled. d) Plastocyanin contains a Type 1 Cu centre. e) Type 2 centre does not give rise to an EPR signal. f) Hemocyanin contains Type 2 Cu centre.
25
WARANGAL
C) an FeMo-protein in which the P-cluster is in an irreversibly reduced state. D) an Fe-only containing protein in which the P-cluster is the active site. 19) Enterobactin is used by microbes to chelate and absorb 1) soluble Fe(II) 2) insoluble Fe(III) 3) soluble Fe(III)
4) insoluble Fe(II)
20) The iron-sulfur protein which does not contain inorganic sulfides is________ . 21) The enzyme which contains cubane like ferredoxin is 1) Carbonic anhydrase 2) Urease 3) Zymase
4) Nitrogenase
23) Biphosphoglycerate stabilizes the T-state of hemoglobin. As a consequence: 1) Affinity of hemoglobin with dioxygen improves in lungs. 2) Affinity of hemoglobin with dioxygen decreases in lungs. 3) More dioxygen is released in the tissues where the pO2 is less. 4) Less dioxygen is released in the tissues where the pO2 is high. 24) The type of cytochrome with lower reduction potential is 1) Cytochrome a 2) Cytochrome b 3) Cytochrome b 4) All with same reduction potentials
25) In cytochrome-c oxidase, the number of iron centres is _____ and the numbe of copper centres is ______ . 26) The metal found at the active site of Rieske protein is a) Ni b) Fe c) Cu
27) The 2Fe-2S protein found in mitochondria and in photosynthetic systems which involve in tranfer of electrons is a) Ferredoxin b) Rubredoxin c) Rieske protein d) All
29) Choose the correct statement about copper proteins. a) EPR sigal is abnormal in Type-II copper proteins. b) Type-III copper proteins are intense blue in color due to MLCT. c) Hemocyanin is a Type-II copper protein. d) Plastocyanin is a Type-I copper protein. 30) Type I and III copper proteins are intense blue in color due to a) LMCT b) d-d transitions c) MLCT
HT
28) The respiratory non heme iron protein containing binuclear iron centre is a) Hemerythrin b) Hemocyanin c) Cytochrome-c d) Hemoglobin
d) Zn d) f-f transitions
22) Which of the following statement is not correct? a) The sixth coordination position in T-state of hemoglobin is occupied by losely bound water molecule. b) The affinity of Hemoglobin with CO will be even more without the presence of distal histidine residue. c) In T-state of hemoglobin, the iron is in low spin and has bigger size (0.78 Ao). d) In R-state of hemoglobin, the iron is in low spin state and has smaller size (0.61 Ao) e) The porphyrin ring in T-state of hemoglobin is dome shaped.
26
WARANGAL
31) EPR signal is absent for which of the following blue copper protein: a) Superoxide dismutase b) Hemocyanin c) Plastocyanin d) Nitrite reductase 32) The number of MgATPs required in the reduction of N2 to ammonia is a) 4 b) 12 c) 16 d) 6 33) The blue copper protein which helps in the transport of iron is a) Ceruloplasmin b) Plastocyanin c) Tyrosinase
d) Nitritereductase
34) The part of nitrogenase enzyme which is involved in transfer of electrons is a) M-cluster b) Molybdenum c) P-cluster d) protein part 35) During the oxidations catalysed by cytochrome P450, one atom of dioxygen enters into the organic substrate and the other atom of oxygen finds its way into a) CO2 b) H2O2 c) H2O d) CO 36) Iron sulfur clusters in biological systems are involved in a) proton transfer b) atom transfer c) group transfer d) electron transfer
HT

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Prepared by V.

Prepared by V. Aditya vardhan

* Oxygen transportation agent

Prepared by V. Aditya vardhan

Prepared by V. Aditya vardhan

Asp OH2 O(Glu) Oxygen Evolving Complex (OEC)

Prepared by V. Aditya vardhan

Function: It catalyzes the conversion of carbondioxide to bicarbonate.

Prepared by V. Aditya vardhan

adichemadi(at)gmail.com OH 2 Zn Cys(S) Cys(S)

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Porphyrin e.g. Heme

Chlorin e.g. Chlorophyll

Corrin e.g. Vitamin B12

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6) The transition metal present in vitamin B12 is_______

8) Match the following 1) Li+ 2) Bi3+ 3) Sb3+ 4) Fe2+

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22) The porphin system in chlorophyll is called as 1) porphyrin 2) chlorin

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Following is Fe2S2 type of ferredoxin.

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Prepared by V. Aditya vardhan

CH2 -CH2 -COO

Desoxy Hb Domed porphyrin High spin Fe(II) - out of ring

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Prepared by V. Aditya vardhan

Prepared by V. Aditya vardhan

step-2 RH N N S(Cys) high spin eN N Fe

S(Cys) low spin

S(Cys) Compound-I with Fe(IV)

Active site of Rubredoxin

Prepared by V. Aditya vardhan

It is a 2Fe-2S protein. It was first discovered and isolated by John S. Rieske.

It is involved in electron transfer in respiration (in mitochondria) and photosynthesis (in

Prepared by V. Aditya vardhan

Prepared by V. Aditya vardhan

1) Methanobactin is a siderophore for absorbing Cu metal. 2) In humans, iron is mobilized by transferrin.

Binding of dioxygen molecule

Formation of ferryl complexes in which iron is in +4 formal oxidation state

Prepared by V. Aditya vardhan

Deoxy form Colorless

Oxy form Violet-pink

Prepared by V. Aditya vardhan

Histidine N O2 N O N Histidine N Histidine N Cu N

Prepared by V. Aditya vardhan

Prepared by V. Aditya vardhan

Prepared by V. Aditya vardhan

Prepared by V. Aditya vardhan

Prepared by V. Aditya vardhan

Prepared by V. Aditya vardhan

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