Bioinorganic Chemistry Flashcards
1
Q
What are the three main types of electron transfer metalloproteins?
A
Cytochromes, FeS cluster, Blue Cu proteins
2
Q
Definition
an enzyme that catalyzes the oxidation of D-galactose in some species of fungi
A
Galactose oxidase
3
Q
Resonance forms of peptides can coordinate to metal centers via what?
A
Can coordinate via N when deprotinated or neutral resonance hybrid, where N is sp3 i.e. has free electron pair
4
Q
What is the dinuclear Fe protein, found in a wide range of enzymes?
A
Haemerythrin
5
Q
Why are elements like Si, Al and Ti not found in the body even thought they have high concentrations in the Earths crust?
A
At pH 7 they all have high oxidation states and exist as nearly insoluble oxides and hydroxides
6
Q
Define
Galactose oxidase
A
an enzyme that catalyzes the oxidation of D-galactose in some species of fungi
7
Q
Definition
a compound or ionic species which can accept an electron pair from a donor compound.
A
Lewis acid
8
Q
If you were given a protein and asked to determine whether it was a ferredoxin or a cytochrome, how would you achieve this experimentally?
A
Addition of HCl would release H2S for the ferredoxin (breakdown of Fe2S2) whereas no inorganic sulfide would be formed with the cytochrome.
9
Q
NAD+ is a ___-electron oxidising agent, and is reduced to NADH
A
NAD+ is a two-electron oxidising agent, and is reduced to NADH
10
Q
Why is zinc used in enzymes?
A
- No CFSE
- Exchanges ligands rapidly
- Forms labile bonds with O-donors (displaced by substrate)
- Forms more inert bonds with N-donors (e.g. with histadine)
- Flexible coordination geometry (CN 4, 5, 6 possible)
- Not redox active
11
Q
What is the entatic state of electron transfer proteins?
A
Metal binding sites are tailored to minimise structural re-organisation that accompanies redox processes
12
Q
_________ structure is created by by R group interactions in an amino acid chain
A
Tertiary
13
Q
What function does cytochrome c perform in mammals?
A
Electron transfer protein in the respiratory chain.
14
Q
Identify this active site for a Zn-metalloproteins
A
Carboxypeptidase (catalytic)
15
Q
Define
Chelate effect
A
the enhanced affinity of chelating ligands for a metal ion compared to the affinity of a collection of similar nonchelating (monodentate) ligands for the same metal
16
Q
Define
Rieske centre
A
iron-sulfur protein (ISP) components of cytochrome bc1 complexes and cytochrome b6f complexes and responsible for electron transfer in some biological systems
17
Q
Definition
a sub-discipline of analytical chemistry covering the quantitative measurement of xenobiotics (drugs and their metabolites, and biological molecules in unnatural locations or concentrations) and biotics (macromolecules, proteins, DNA, large molecule drugs, metabolites) in biological systems
A
Bioanalysis
18
Q
Definition
a copper-containing enzyme which catalyses the formation of quinones from phenols and polyphenols (e.g. melanin from tyrosine)
A
Tyrosinase
19
Q
Paramagnetic
A
very weakly attracted by the poles of a magnet, but not retaining any permanent magnetism.
20
Q
Definition
an enzyme that catalyses the interconversion of dissolved bicarbonates and carbon dioxide
A
Carbonic anhydrase
21
Q
Define
Oxygenase
A
any enzyme that oxidizes a substrate by transferring the oxygen from molecular oxygen O2 (as in air) to it
22
Q
What is the simplest Ferredoxin?
A
23
Q
Model complexes of Hr show what?
A
Spontaneous self-assembly but without a vacant coordination site for O2
24
Q
Define
Blue copper proteins
A
An electron transfer protein containing a type 1 copper site with coordination of the copper by a cysteine sulfur
25
Sketch the ‘coordination environment’ of the active site of the blue copper protein, plastocyanin. How does this ‘geometry’ assist the protein perform its function?
Entatic state: the geometry imposed on the Cu ion is suited to neither 1+/2+ oxidation state, however, the geometry imposed is that close to the transition state complex, hence facilitates electron transfer.
26
# Definition
any of a class of pigments (including haem and chlorophyll) whose molecules contain a flat ring of four linked heterocyclic groups, sometimes with a central metal atom
Porphyrins
27
# Define
Biomimetic compounds
a compound that mimics a biological material in its structure or function
28
What does carbonic anhydrase do?
Catalyses the reaction of the reversible hydration of CO2 to form the bicarbonate + H+ @ a rate ~ 1 x 107 s-1
29
What happens to the structure of electron transfer metalloproteins as a result of oxidation/reduction? What does this do to reaction rates?
These metal redox centres undergo minimal structural change. This minimises the activation barrier associated with electron exchange and optimises electron transfer rates
30
Diamagnetic
tending to become magnetized in a direction at 180° to the applied magnetic field.
31
What are the changes in spin state that you would predict during dioxygen binding to myoglobin? Justify your answer….
The deoxymyoglobin is initially reduced, hs, 3 d6 and on coordination with O2 the binding of an addition ligand will increase the crystal field strength, hence a shift to low spin is expected. Also, there is transfer of an electron to the oxygen (FeIII-O2 1- ). The low spin, hexa-coordinated iron has one unpaired spin that couples to the superoxide radical, creating a diamagnetic complex.
32
Name three different proteins that transport oxygen?
haemoglobin | myoglobin
haemerythrin
haemocyanin
33
Zinc ions are ‘spectroscopically silent’ which makes it difficult to explore the reaction of Zn-metalloproteins in detail. How can this limitation be overcome? And what information can be obtained using your method?
Co2+ can be used to substitute for Zn2+ ions in the active site complex.
This provides spectroscopic information on coordination geometry, and monitoring the electronic spectrum with pH indicates deprotonation of coordinated water. Thus the reaction kinetics and mechanism can be ascertained
34
Give a brief description of (ii) a metalloprotein
Metalloprotein is a generic term for a protein that contains a metal ion cofactor.
35
# Definition
any enzyme that oxidizes a substrate by transferring the oxygen from molecular oxygen O2 (as in air) to it
Oxygenase
36
How are Fe-S centres similar/different to cytochromes?
They are similar also undergoing minimal structural change, although they are high spin.
The ligands do no point towards the metal d-orbitals
37
What element is relatively redox inactive?
Zinc
38
What are the disadvantages of working with Zn2+?
Zn2+ has 3d10 electronic configuration, so has no electronic spectrum (UV-vis) and no magnetic properties
39
# Definition
iron-sulfur protein (ISP) components of cytochrome bc1 complexes and cytochrome b6f complexes and responsible for electron transfer in some biological systems
Rieske centre
40
Which oxygen species is diamagnetic?
Peroxide
41
Why is the change from deoxy- haemoglobin to oxy- haemoglobin accompanied by a decrease in its observed magnetic moment?
As oxygen binds deoxy- haemoglobin there is an electron transfer between the Fe(II) → O2 0 =\> Fe(III) → O2 1- , and the unpaired electron (t2g5 eg) on the Fe3+ couples to the superoxide ‘antiferromagnetic coupling’ to make a diamagnetic complex.
42
# Define
Oxidase
an enzyme which promotes the transfer of a hydrogen atom from a particular substrate to an oxygen molecule, forming water or hydrogen peroxide
43
What happens when ΔG is negative?
A process or chemical reaction proceeds spontaneously in the forward direction
44
What Fe and Cu proteins are involved as elecrtron carriers?
Cytochromes
Iron sulfur proteins
Blue copper proteins
45
Why is it so difficult to prepare synthetic model complexes for Mb (or Hb) oxygen transport proteins; ie the heme = Fe porphyrin’s?
Due to the formation of oxo-bridged dimers of the Fe porphyrin.
46
As oxygen binds to a heme group, subsequent oxygen groups attach more easily in a show of _______ binding
Cooperative
47
What is the origin of the intense absorption band at ~600 nm for plastocyanin?
It occurs due to the Sulfur to copper charge transfer
48
Tyrosinase
a copper-containing enzyme which catalyses the formation of quinones from phenols and polyphenols (e.g. melanin from tyrosine)
49
Identify this active site for a Zn-metalloproteins
Carbonic anhydrase (catalytic)
50
Describe the structure of the copper site in plastocyanin and discuss the features of both metal centre and the metal binding site that allow it to function as an electron transport protein.
The geometry of the copper binding site is described as a ‘distorted tetrahedral’. Two ligands are nitrogen atoms from separate histidine residues and the other two from a sulfur atom from a cysteine residue. The ‘distortion’ occurs in the bond lengths between the copper atom and sulfur ligands. The Cu-S1 contact is much shorter (2.07 Å) than Cu-S2 (2.82 Å). The elongated Cu-S2 bonding destabilises the CuII form and increases the redox potential of the protein. The blue colour ( max 597 nm absorption) is due to the Cu-S1 bond where Spπ to Cudx2 -y 2 charge transfer occurs The distortion of geometry for plastocyanin, is between that preferred by Cu2+ and Cu+ , close to the transition state geometry. Thus there is very little bond-length changes and no spin state change needed during electron transfer, hence rapid.
51
How many Fe's can there be at the "core" of ferredoxins?
Up to 4
52
What makes up the active site of the cytochrome p450 enzyme?
Heme, cys (thiolate) and water (resting)
53
Prosthetic group
a non-protein group forming part of or combined with a protein
54
Where are Cu|Zn SOD found in eukaryotic cells?
Cytoplasm, mitochondria and extracellular space
55
What happens if the metal is oxidised without being bound to oxygen? What prefix do we give these states?
It is unable to bind oxygen and a reductase is required to reduce the atom. We give them the prefix met-
56
# Definition
iron–sulfur proteins that mediate electron transfer in a range of metabolic reactions
Ferredoxins
57
How does a multicellular organism manage to concentrate metal ions for a specific function?
Biology has mechanisms to compartmentalise and actively transport and accumulate inorganics. Generally, ions of low charge exchange rapidly and higher charged ions have longer "half-lives"
58
# Definition
An electron transfer protein containing a type 1 copper site with coordination of the copper by a cysteine sulfur
Blue copper proteins
59
A carboxylate group can exhibit monodentate, bridging or ________ characteristics
Bidentate/chelating
60
What makes up the active centre of alcohol dehydrogenase?
Zn bound to 1 histidine (neutral) and 2 cysteine (anionic) side chains and oxygen atom of alcoholate/aldehyde (coordinated RCH2O- )
61
True or False:
Alcohol dehydrogenase is a monomer
False
It is a dimer with 2 catalystic Zn and 2 structural Zn
62
Why is metal ion substitution used to investigate the metal binding site of carbonic anhydrase? Discuss the type of information that might be obtained from such a study?
As Zn2+ is colourless, and diamagnetic, it is difficult to follow or probe reactions involving zinc ions. Fortunately, Co2+ is able to exchange (isomorphous) with zinc site in metalloenzymes, anf the high spin Co2+, 3d7 , is coloured and similar size with a common Td geometry.
63
# Definition
an enzyme that catalyses the hydrolysis of a particular substrate
Hydrolases
64
Why do you think histidine is often found at the ‘active-site’ of a metalloprotein?
Histidine donor atoms are heterocyclic nitrogens and are intermediate in HSAB definition, so can best accommodate both the hard(er) higher oxidation states and the soft(er) lower oxidation states, during redox cycling.
65
True or False:
Fe-O2 bond is kinetically but not thermodynamically stabilised
True
66
What creates a chemical process that converts tyrosine to indolquinone?
Tyrosinase
67
True or False:
Zinc is a good Lewis Acid
True
68
# Define
Rubredoxin
a class of low-molecular-weight iron-containing proteins found in sulfur-metabolizing bacteria and archaea
69
Insoluble polymerising Hb(forms fibres) is \_\_\_\_\_\_\_\_\_celled Hb
Deoxy-sickle
70
What is a molecule that binds to a protein to enable biological activity called?
Cofactor
71
What does bioavailability mean?
the proportion of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect
72
Draw the reaction carried out by carbonic anhydrase
73
# Definition
a heterocyclic compound. It is the parent macrocycle related to the substituted derivative that is found in vitamin B12
Corrin
74
What happens to a reducing agent?
It loses an electron during the reaction and is this oxidised
75
# Define
Haemerythryn
a non-heme iron protein used by two phyla of marine invertebrates (sipunculids and brachiopods) for oxygen transfer and/or storage
76
Comment on the bioavailablity of oxidized copper ions compared to reduced copper ions in sea water.
Bioavailability of metals is where they are present in high concentrations in sea water and the earths crust, therefore ‘available’ for uptake by organisms. Oxidised Cu i.e. Cu2+ is expected to be bioavailable in an oxidising atmosphere, and is soluble as [Cu(H2O)6] 2+(aq), whereas the reduced form, Cu1+ was not available due to insoluble and CuS .
77
What oxidatively dehydrogenates substrate, and then reduces oxygen to water?
Oxidase
78
# Define
Alcohol dehydrogenase
a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH
79
# Define
Transferrin
a protein of the beta globulin group which binds and transports iron in blood serum
80
True or False:
For proteins, electron transfer must always be via outer-sphere electron transfer
True
81
# Define
Entatic state
a state of an atom or group which, due to its binding in a protein, has its geometric or electronic condition adapted for function
82
What is the function of haemoglobin?
It carries oxygen to cells for respiration and carbon dioxide to the lungs for removal
83
What metalloprotein do arthropods and molluscs have?
Hemocyanin
84
# Define
Haemoglobin
a red protein responsible for transporting oxygen in the blood of vertebrates. Its molecule comprises four subunits, each containing an iron atom bound to a haem group
85
Cooperative binding
a type of bonding that occurs in binding systems containing more than one type, or species, of molecule and in which one of the partners is not mono-valent and can bind more than one molecule of the other species
86
# Definition
an enzyme which catalyses the conversion of a specified compound to an isomer
Isomerases
87
88
Draw the reaction carried out by carboxypeptidase A
89
What Fe and Cu proteins are involved in oxygen management?
Myoglobin
Haemoglobin
Haemerythryn
Haemocyanin
90
Give a brief description of (i) the four different levels of structure for a protein polypeptide
1. Primary: - The primary structure of a protein refers to the sequence of amino acids in the polypeptide chain. The primary structure is held together by peptide bonds that are made during the process of protein biosynthesis. Secondary: - Protein secondary structure is the three dimensional form of local segments of proteins. Secondary structure is formally defined by the pattern of hydrogen bonds between the amino hydrogen and carboxyl oxygen atoms in the peptide backbone. Tertiary: - Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Quarternary: - The quaternary structure is the arrangement of more than one protein molecule in a multi-subunit complex.
91
What is the nature of the oxidation state of a metal with hard ligands bonded?
High oxidation state (ionic bonds to ligands)
92
List 4 types of non-covalent bonding?
Ionic
Van der Waals
Hydrogen
Hydrophobic
93
Describe the action of Cu|Zn SOD
1. The first O2 •- anion is coordinated to Cu2+ , stabilised via a ionic (salt bridge) interactions with the =NH2 + moiety of an adjacent arginine.
2. O2 •- reduces Cu2+ to Cu+, resulting in self oxidation to the neutral O2, which is released. A second O2 •- coordinates to Cu+ with simultaneous protonation of the bridging histidine, that detaches from the Cu+ ion
3. Cu+ reduces the coordinated O2 •- to O2 2- (Cu+ oxidised to Cu2+), and the O2 2- protonated to HO2 - (hydroperoxide)
4. Initial state recovered, by release of H2O2, protonation of arginine and re-establishment of the Cu+-his(1-) bond.
94
•Classify the following metals as either hard, soft or intermediate:
Na+, Ca2+, Fe3+, Fe2+, Cu2+, Cu+, Co2+
Na+ , hard
Ca2+ hard
Fe3+ hard
Fe2+ intermediate
Cu2+ intermediate
Cu+ soft
Co2+ intermediate
95
# Define
Histadine
an α-amino acid that is used in the biosynthesis of proteins.
96
Why is zinc well suited for catalysing acid-base reactions?
it is abundant, redox in-active, forms strong bonds to donor groups of amino acid residues, and exogenous ligands such as water are exchanged rapidly
97
What is a single polypeptide attached to haem?
Myoglobin
98
# Define
Cytochromes
any of a number of compounds consisting of haem bonded to a protein. They function as electron transfer agents in many metabolic pathways, especially cellular respiration
99
Which metalloproteins are involved in mammalian oxygen transport?
Hemoglobin and myoglobin
100
i. What is the ground state electronic configuration (3dn) for Fe3+?
ii. Assuming an Oh crystal field splitting, draw the orbital occupancy for a highspin and a low spin complex.
iii. Calculate the spin-only magnetic moment for both spin states
3d5
101
What is the reduction potential trends of Hemes, Fe-S and Cu?
Cu (+ve) \> heme (0) \> Fe-S (-ve)
Although this is only a guide, it helps to explain the tendency of Cu and heme to be oxidising centres, and Fe-S as a reducing centre in redox enzymes
102
What Fe and Cu proteins are involved in metal management?
Ferratin
Transferrin
Ceruloplasmin
103
What element can replace zinc for experimental applications?
Cobalt
104
Give a brief description of (iii) the haem group
Haem (or heme) is a coordination complex "consisting of an iron ion coordinated to a porphyrin acting as a tetradentate ligand, and to one or two axial ligands." The definition is loose, and many depictions omit the axial ligands. Many porphyrincontaining metalloproteins have haem as their prosthetic group; these are known as haemoproteins.
105
Iron-sulfur cluster operate at more ______ potentials than cytochrome; theu are composed of \_\_\_\_-spin Fe(III) or Fe(II) with sulfur ligands in a mainly tetrahedral environment
Iron-sulfur cluster operate at more **negative** potentials than cytochrome; theu are composed of **high**-spin Fe(III) or Fe(II) with sulfur ligands in a mainly tetrahedral environment
106
# Define
Outer-sphere electron transfer
an electron transfer (ET) event that occurs between chemical species that remain separate and intact before, during, and after the ET event
107
Why can Co2+ be substituted for Zn2+?
* The ionic radius of the two ions is similar
* Co2+ tolerates similar geometries to Zn2+
* Generally, substitution of Co2+ for Zn2+ doesn’t perturb the protein conformation
108
# Definition
a red protein responsible for transporting oxygen in the blood of vertebrates. Its molecule comprises four subunits, each containing an iron atom bound to a haem group
Haemoglobin
109
# Define
Blue copper oxidase
enzyme which catalyzes the conversion of Cu+1 to Cu+2 resulting in the detoxification of copper by the prevention of its uptake into the cytoplasm
110
How is the heme group attached in myoglobin?
It is attached via the proximal histidine
111
Draw the structure of the ligand alanine, and using a balanced reaction, indicate how it might react with Copper sulfate to form a stable coordination complex.
(b) is this complex likely to be paramagnetic or diamagnetic? Indicate a reason for your answer.
Paramagnetic, as Cu2+ is 3d9 , hence in all geometries, including octahedral, tetrahedral, square planar and square pyramidal, there is always one unpaired electron in the d-orbitals.
112
# Define
Lewis acid
a compound or ionic species which can accept an electron pair from a donor compound.
113
# Definition
an electron transfer (ET) event that occurs between chemical species that remain separate and intact before, during, and after the ET event
Outer-sphere electron transfer
114
What happens to the spin state when myoglobin is oxygenated?
It goes from high spin (d6) to low spin. An electron is then tranferred from Fe to O2 making the Fe d5. The spins then couple making the diamagnetic
115
# Definition
an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor
Oxidoreductases
116
What exopeptidase hydrolyses peptide bonds?
Carboxypeptidase
117
What is the radical anion side product of metabolism called?
Superoxide
118
NAD+ + ______ → NADH
NAD+ + **H+ + 2e- (or H-)** → NADH
119
What happens to the oxygen when it binds to the Fe in hemoglobin?
It is reduced to superoxide
120
Compare the reduction potentials for the copper complexes, 1 and 2. Explain the trends using the data provided.
* The more negative Eo’ values stabilise the Cu2+ state
* The harder Cu2+ prefers O- to N-donors, and square planar/square pyramidal/tetragonal preferred by Cu2+ than Cu+ that prefers tetrahedral (Td)
* For 1, R=(CH3)3C- square planar is not possible…., so complex is forced to adopt Td Þ better for Cu+ & Eo’ less negative
* For 2, the softer S- ligand prefers Cu+ so & Eo’ less negative when X = S
* Comparison of 1 & 2, ligand 2 is more rigid, and thus favours the square planar geometry that Cu2+ so, Eo’ 2 more negative , Eo’ 1
121
# Definition
an enzyme which promotes the transfer of a hydrogen atom from a particular substrate to an oxygen molecule, forming water or hydrogen peroxide
Oxidase
122
# Define
Ferredoxins
iron–sulfur proteins that mediate electron transfer in a range of metabolic reactions
123
What spin state and coordinate are cytochromes in in a reduced state? How many axial ligands do they have?
They are 6 coordinate, low spin, with 2 axial ligands
124
What distorts the geometry for Cu2+ and Cu+ in Blue Cu proteins?
They have a ligand donor set that is held firmly by the protein polypeptide that distorts it
125
# Definition
an enzyme that catalyzes the linking together of two molecules especially by using the energy derived from the concurrent splitting off of a pyrophosphate group from a triphosphate (as ATP)
Synthetases
126
Model compounds are often used to model iron-sulfur proteins. Comment on the why this redox system is (i) widely used in nature and (ii) found in ancient bacteria. (iii) If you were synthesising (or just designing) an iron-sulfur protein, write a balanced equation for how this would be achieved.
(i) thermally robust ‘existing in thermophilic bacteria.
(ii) iron-sulfur proteins are ancient, found across all primitive life forms as well as higher species. Reduced Fe, and inorganic S 2- were common in primitive environments.
(iii) Fe3+ + 2 S2- + thiolate containing ligand → [Fe2S2](thiol)2 (1 +
127
What are the oxidation states of the Cu in the deoxy and oxy hemocyanin molecules?
Deoxy = 1+
Oxy = 2+
128
Discuss the role of Zn2+ as an example of a Lewis Acid functioning in a biological system.
Zinc is the second most abundant transition metal in humans. The properties, under physiological conditions is it is a dication, diamagnetic (3d10) and colourless, means it is not easily excited and redox inactive =\> stable. Zn enzymes have two major functions; structural role coordinating S, N and O ligands and as a Lewis acid, leading to acid-base reactions, thus able to catalyse condensation and hydrolysis reactions.
129
True or False:
Oxygen is a poor Lewis acid and Lewis base
True
130
Is Fe expected to be present in the cells as an uncomplexed ion?
No, Fe forms coordination complexes in the cell as the uncomplexed ion is practically insoluble at pH 7
131
# Define
Superoxide dismutase
a metal-containing antioxidant enzyme that reduces harmful free radicals of oxygen formed during normal metabolic cell processes to oxygen and hydrogen peroxide
132
# Define
Carbonic anhydrase
an enzyme that catalyses the interconversion of dissolved bicarbonates and carbon dioxide
133
# Definition
a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH
Alcohol dehydrogenase
134
Comment on the following observations: (ii) Two different metalloproteins, both containing [4Fe4S] ferredoxins bound to the protein polypeptide by cysteine ligands, exhibit reduction potentials +350 mV and +490 mV.
The redox potentials of FeS containing protein (ferredoxins) are influenced by local amino acids and distortions form the ideal geometry. Thus these two [4Fe4S] must exist in very different environment.
135
What are eletron transfer proteins characterised by?
Redox centres that are structurally designed to facilitate rapid and efficient electron transfer
136
What is an apoenzyme?
an inactive enzyme
137
Define the term “entatic” state. Briefly describe how this is important for electron transfer proteins.
An entatic state occurs where the geometry enforced in a protein optimises, eg. the rate of electron transfer hence function. This geometric distortion minimises the reorganisational energy (changes in bond lengths, angles during electron transfer).
eg. An example of an entatic state is the copper centre in a redox protein plastocyanin.
138
What components make up a a holoenzyme?
Apoenzyme and cofactor
139
What is the overall two step process of Cu|Zn SOD?
CuII + O2- → CuI + O2
CuI + O2- +2H+ → CuII + H2O2
140
# Definition
a compound that mimics a biological material in its structure or function
Biomimetic compounds
141
Why does Sickle cell anemia lead to reduced oxygen transport?
The mutation means that no cooperative binding can occur meaning that less oxygen is transported to the tissues
142
What is the copper protein for oxygen transport (found in arthropods)?
Haemocyanin
143
# Define
Iron sulfur proteins
proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetra iron centers in variable oxidation states
144
# Define
Hydrolases
an enzyme that catalyses the hydrolysis of a particular substrate
145
What happens to an oxidising reagent?
It gains an electron during the reaction and is this reduced
146
A chain of amino acids held together by peptide binds is the ________ structure
Primary
147
# Define
Carboxypeptidase
a protease enzyme that hydrolyzes (cleaves) a peptide bond at the carboxy-terminal (C-terminal) end of a protein or peptide
148
What does the Zn2+ do in the Cu|Zn SOD?
Ensure structural integrity of the protein but is not involved in the electron transfer
149
What does E0 need to be if the reaction occurs spontaneously?
Positive E0
150
# Definition
a metal-containing antioxidant enzyme that reduces harmful free radicals of oxygen formed during normal metabolic cell processes to oxygen and hydrogen peroxide
Superoxide dismutase
151
the binding of O2 to haemoglobin exhibits a ‘cooperativity’ effect. What is meant by this statement?
Cooperativity is where identical or near-identical elements, act in a dependent manner, rather than acting independently. Where an oxygen binds to one of haemoglobin's four binding sites, the affinity to oxygen of the three remaining available binding sites increases; i.e. oxygen is more likely to bind to a haemoglobin bound to one oxygen than to an unbound haemoglobin.
152
How many electrons do transition metals transfer?
1 electron
153
Which metaloproteins has side-on binding?
Hemocyanin
154
Model complexes of Hb (Mb) require what to prevent the formation of oxo-bridge porphyrins?
Piclet fencing or large straps
155
What happens when heme is by itself in solution?
A dimer will form
156
# Definition
a class of low-molecular-weight iron-containing proteins found in sulfur-metabolizing bacteria and archaea
Rubredoxin
157
Identify this active site for a Zn-metalloproteins
Structural
158
# Define
Isomerases
an enzyme which catalyses the conversion of a specified compound to an isomer
159
How are Fe-S clusters defined?
By the number of iron ions in the prosthetic centre
* (1Fe) rubredoxin (Rd)
* (2Fe) ferredoxin (Fd)
* (4Fe) ferredoxin (Fd)
* (4Fe) Can be further divided into low- and high-potential
160
What are the wavelength maxima and solubility properties of Cytochrome a, b and c?
Cyt. a = longest λmax
Cyt. b = intermediate λmax (less soluble)
Cyt. c = shortest λmax (water soluble)
161
# Define
Pterin
a heterocyclic compound composed of a pteridine ring system, with a "keto group" (a lactam) and an amino group on positions 4 and 2 respectively
162
Anti-ferromagnetic coupling
In materials that exhibit this, the magnetic moments of atoms or molecules, usually related to the spins of electrons, align in a regular pattern with neighboring spins (on different sublattices) pointing in opposite directions.
163
# Definition
a heterocyclic compound composed of a pteridine ring system, with a "keto group" (a lactam) and an amino group on positions 4 and 2 respectively
Pterin
164
# Definition
a protease enzyme that hydrolyzes (cleaves) a peptide bond at the carboxy-terminal (C-terminal) end of a protein or peptide
Carboxypeptidase
165
Why are aerobic organisms dominant on Earth?
Oxygen is a powerful oxidant
166
# Define
Lewis base
a compound or ionic species which can donate an electron pair to an acceptor compound
167
# Definition
an α-amino acid that is used in the biosynthesis of proteins.
Histadine
168
What happens to the oxygen when it binds to a non-heme protein?
It is reduced to peroxide
169
Identify this active site for a Zn-metalloproteins
Carboxypeptidase (catalytic)
170
# Define
Corrin
a heterocyclic compound. It is the parent macrocycle related to the substituted derivative that is found in vitamin B12
171
Describe all the changes in the metal and ligands including any spin state changes that you would predict during oxygen binding to Hb?
There is an electron transfer between the Fe(II) → O2 0 =\> Fe(III) → O2 1- , and the unpaired electron (t2g5 eg) on the Fe3+ couples to the superoxide ‘antiferromagnetic coupling’ to make a diamagnetic complex.
172
# Definition
a compound or ionic species which can donate an electron pair to an acceptor compound
Lewis base
173
Two amino acid chains joining together creates a __________ structure
Quarternary
174
# Definition
a red protein containing haem, which carries and stores oxygen in muscle cells. It is structurally similar to a subunit of haemoglobin
Myoglobin
175
# Definition
A type of cofactor that is an organic non-protein molecule that carries chemical groups between enzymes, often from vitamins, and can be tightly or loosely bound
Coenzyme
176
What occurs when Zn(II) acts as a Lewis acid?
Zn-carbonyl
177
Mo is found in low concentrations in the earths crust so why is it found within the body?
It is bioavailable as MoO42-, i.e. a water soluble species at pH 7
178
Evolutionarily, how did this have an impact on the development of “parallel” analogues to iron metalloproteins.
The primitive environment on earth, was reducing so that, Fe existed as Fe2+ and Cu1+ was not available due to insoluble and CuS . Later when oxygen-rich atmosphere appeared, Cu was oxidised into the water soluble Cu2+ and Fe3+ was no longer soluble, as it formed the insoluble Fe2O3 or Fe(OH)3 Thus we have parallel roles for Fe and Cu in many essential biological function, eg. Transport of oxygen and electron transfer proteins.
179
# Define
Ceruloplasmin
a ferroxidase enzyme that in humans is encoded by the CP gene. It is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism
180
What is the advantage of ferredoxin over rubredoxin?
By combining the metal centres it provides a wider range of potentials
181
Identify this active site for a Zn-metalloproteins
Alcohol dehydrogenase (catalytic)
182
# Definition
small molecule that binds to a protein and is needed for biological activity
Cofactor
183
What are oxidases?
Any enzymes that get oxidised and reduced oxygen
184
# Define
Coenzyme
A type of cofactor that is an organic non-protein molecule that carries chemical groups between enzymes, often from vitamins, and can be tightly or loosely bound
185
Why is Mo found in the body even thought it has low concentrations in the Earths crust?
It is bioavailable as MoO42- which is water soluble at pH 7
186
A metal complex with six ligands is typically in _________ coordination according to CFSE
Octahedral
187
Although, molybdenum is rare in the earths crust, it is an essential metal for life. However, chemically it is a bit peculiar, being the only metal ion from the second (4d) series of transition metal ions with biological function. Briefly comment on the chemistry of molybdenum and why it is so bioavailable.
Elements are incorporated into biological systems, based on availability and chemical properties. So Al, Si & Ti are available in the earths’ crust as at pH ~7, they exist in high oxidation states as insoluble oxides, thus not bioavailable. Mo is quite low conc. in the earth crust, but forms a water soluble oxide MoO4 2- at neutral pH, this is bioavailable. This solubility contrasts those heavy metals (second|third d-block) to the left of Mo, which are mostly insoluble @ pH 7, whereas, elements to the right of Mo, are too rare to be biologically significant.
188
Why are proton and electron transfers usually coupled?
To ensure that there is an overall neutral charge
189
What brings both atoms of an O2 molecule into a substrate?
Dioxygenase
190
What are the two main ways that Na + and K+ are transported across the membrane?
There is ~ 15 fold excess of Na+/K+ in the extracellular space, ratio reverses in intracellular space …
1. Transport is by passive diffusion, which is slow, or ionophores (macrocycles)
2. Or active transport, via Na+/K+-pump (ATPase) where 2 K+ pumped inside with 3 Na+ pumped outside the cell.
191
What is the function of alcohol dehydrogenase?
Catalyses the oxidation of primary alcohols to aldehydes
192
What is required for peptide hydrolysis to occur?
1. facilitate a nucleophilic attack on the peptide carbonyl group by generating a reactive nucleophile and/or activating the C=O carbonyl group
2. stabilize the tetrahedral carbon intermediate
3. activate the amide nitrogen atom to form a suitable leaving group (to break the peptide C-N bond)
193
For a [4Fe4S] protein, the following series of redox reactions are possible. In which step is this protein able to function as a one electron transfer protein in physiological conditions.
4Fe(III) ⇌3Fe(III).Fe(II) ⇌2Fe(III).2Fe(II) ⇌Fe(III).3Fe(II) ⇌4Fe(II)
In the normal [4Fe4S] proteins, function as [4Fe4S]2+/+. This equates formally as 2Fe(III).2Fe(II) ⇌Fe(III).3Fe(II)
194
What is made of two alpha and two beta protein subunits, and carries oxygen?
Haemoglobin
195
What oxidation state is the Fe in in both the deoxy and oxy-proteins?
Deoxy = 2+
Oxy = 3+
196
(i) Describe the differences and similarities between the haem units in deoxymyoglobin and cytochrome c.
deoxymyoglobin: 5 coordinate geometry around the Fe ion i.e. haem N4+His
cytochrome c: 6 coordinate geometry around the Fe ion haem N4+2 His
197
# Definition
enzyme which catalyzes the conversion of Cu+1 to Cu+2 resulting in the detoxification of copper by the prevention of its uptake into the cytoplasm
Blue copper oxidase
198
How can ΔG and E0 be related in an equation?
Nerst Equation:
ΔG = -n F E0
(F = Faraday's, n = number of electrons)
199
The d-orbitals in cytochromes *do/do not* point towards the ligands.
What does this mean for the structural arrangement during electron transfer?
The d-orbitals in cytochromes **do not** point towards the ligands.
Hence there is minimal structural arrangement in electron transfer reaction, Fe3+/2+
200
What does Tyrosinase do?
Catalyses successive hydroxylations of phenols to ohydroquinones (oxygenase activity) and the oxidation of hydroquinones to quinones (oxidase activity)
201
What is cooperative binding in relation to hemoglobin?
oxygen binding increases the affinity ofhemoglobin for more oxygen. Increased affinity is caused by a conformational change, or a structural change in thehemoglobin molecule.
202
Briefly describe the mode of binding of oxygen to the iron centre in one unit of haemoglobin.
The iron (high spin Fe(II)), lies out of the N4 plane. On coordination to an O2 molecule, the Fe → low spin, (small radius) and goes into the N4 plane.
203
What is the structure of tyrosinases?
Tyrosinases have two Cu centres (type 3; similar to hemocyanin), both with a trigonal-pyramidal coordination geometry with His ligands
204
What are the picket fence porphyrins and comments on why they are used in model studies of O2 binding to myoglobin and haemoglobin.
Model complexes for haemoglobin were challenging to prepare, as -oxo-dimers form readily, preventing ‘reversible’ oxygen binding complexes. The ‘picket fence porphyrins’ were one class of model complex to be synthesised, where vertical ‘pickets’ are located on one face of the porphyrin, such that they created steric crowding that prevented -oxo-dimers from forming, yet were able to bind oxygen.
205
What are the three main types of Zn enzymes?
Carboxypeptidase
Carbonic anhydrase
Alcohol dehydrogenase
206
Comment on the similarities and differences between a [2Fe-2S] ferredoxin and a Rieske protein, in terms of structure and function.
The coordination of 2 x His + 2 x Cys (Rieske protein), replacing 4 x Cys in the [2Fe-2S] ferredoxins, raises the redox potential from -420 → +280 mV. Importantly, the ligands are unsymmetrically coordinated in the Rieske protein. These are found where intramembranes (mitochondria) electron transfer occurs, and enables electrons to flow from the 2 e donor hydroquinones → (split) into a low potential pathway (cyt b) and a high potential pathway (Rieske protein).
207
• Sketch the ‘coordination environment’ of the active site of a zinc metalloenzyme. Why are the ligands from the protein good for the enzymes function?
Eg. Carbonic anhydrase – 3 x His
These are all neutral ligands, thus making the Lewis acidity towards the coordinated water more effective.
208
# Definition
a non-heme iron protein used by two phyla of marine invertebrates (sipunculids and brachiopods) for oxygen transfer and/or storage
Haemerythryn
209
Comment on the following observations: (i) Blue copper proteins’ are not always blue?
The blue colour of ‘Blue copper proteins’ arises from the Cu2+ (oxidized) comes form LMCT band from S(cys) → CuII. The reduced form, is CuI , thus 3d10 and colourless.
210
# Define
Cofactor
small molecule that binds to a protein and is needed for biological activity
211
# Define
Ferratin
a protein produced in mammalian metabolism which serves to store iron in the tissues.
212
# Define
Synthetases
an enzyme that catalyzes the linking together of two molecules especially by using the energy derived from the concurrent splitting off of a pyrophosphate group from a triphosphate (as ATP)
213
How doe Blue copper proteins overcome a large inherent difference in preference for geometries between Cu(II) and Cu(I)?
By constraining Cu in a coordination environment that does not change on electron transfers
214
\_\_\_ enzymes tend to be extracellular (oxidising) synthesised inside cells then exported, but ___ enzymes function inside the cell (reducing)
**Cu** enzymes tend to be extracellular (oxidising) synthesised inside cells then exported, but **Fe** enzymes function inside the cell (reducing)
215
Draw the molecular structure of the amino acid histidine. Indicate the possible ‘modes’ of coordination via the side chain moiety.
216
# Definition
any of a number of compounds consisting of haem bonded to a protein. They function as electron transfer agents in many metabolic pathways, especially cellular respiration
Cytochromes
217
# Definition
the enhanced affinity of chelating ligands for a metal ion compared to the affinity of a collection of similar nonchelating (monodentate) ligands for the same metal
Chelate effect
218
# Define
Oxidoreductases
an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor
219
True or False:
O2 is a powerful reductant
False
O2 is a powerful **oxidant**
220
Cytochrome operate in the potential region \_\_\_\_\_\_\_\_\_\_\_\_\_; they have a combination of ____ reorganisational energy and extended electronic coupling through delocalised orbitals
Cytochrome operate in the potential region **-0.3 - +0.4 V**; they have a combination of **low** reorganisational energy and extended electronic coupling through delocalised orbitals
221
\_\_\_\_\_\_\_ structure formed by hydrogen bonding between peptide bonds at different points in the chain
Secondary
222
# Definition
a protein containing copper, responsible for transporting oxygen in the blood plasma of arthropods and molluscs
Haemocyanin
223
# Define
Porphyrins
any of a class of pigments (including haem and chlorophyll) whose molecules contain a flat ring of four linked heterocyclic groups, sometimes with a central metal atom
224
Cysteine often will form ________ bonds with other cysteine residues
Disulfide
225
What is the nature of the oxidation state of a metal with soft ligands bonded?
Low oxidation state (Covalent bond, more diffuse electron state)
226
Why is Zinc used in acid-base catalysis reactions in biology?
Zinc is well suited for catalysing acid-base reactions as it is abundant, redox in-active, forms strong bonds to donor groups of amino acid residues, and exogenous ligands such as water are exchanged rapidly.
227
What is the primary function of the cytochrome p450 enzyme?
Hydroxylation (i.e. C-H into C-O(H))
228
# Define
Bioanalysis
a sub-discipline of analytical chemistry covering the quantitative measurement of xenobiotics (drugs and their metabolites, and biological molecules in unnatural locations or concentrations) and biotics (macromolecules, proteins, DNA, large molecule drugs, metabolites) in biological systems
229
What is the structural differences between myoglobin and hemoglobin?
Mb is a monomer which Hb is a tetramer
230
What amine acid stabilises oxygen bound to iron?
Histadine
231
What is the structure of haemoglobin?
Haemoglobin is made up of four protein subunits wach containing a haem group, binding Fe, needed to bind oxygen
232
What happens to hemoglobins affinity for oxygen has the concentration of oxygen decreases?
Affinity decreases (i.e. the oxygen is released from the Hb)
233
# Definition
a protein produced in mammalian metabolism which serves to store iron in the tissues.
Ferratin
234
What do FeS proteins contain?
High spin Fe(II) or Fe(III) coordinated tetrahedrally by four S-donors (S2- or -S-cys)
235
# Define
Haemocyanin
a protein containing copper, responsible for transporting oxygen in the blood plasma of arthropods and molluscs
236
# Define
Myoglobin
a red protein containing haem, which carries and stores oxygen in muscle cells. It is structurally similar to a subunit of haemoglobin
237
Model complexes of Hc show what?
Stabilisation of the side-on mode of O2 coordination at extremely low temperatures
238
# Definition
a ferroxidase enzyme that in humans is encoded by the CP gene. It is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism
Ceruloplasmin
239
# Definition
a protein of the beta globulin group which binds and transports iron in blood serum
Transferrin
240
# Definition
a state of an atom or group which, due to its binding in a protein, has its geometric or electronic condition adapted for function
Entatic state
241
A reduced oxygen-free form of a complex is called a \_\_\_\_\_\_\_
Deoxy-
242
Classify the following ligands as either hard, soft or intermediate:
H2O, NH3, C2H5S- , F- , pyridine, edta4- , Br- , I-
H2O, hard
NH3, hard
C2H5S- , soft
F- hard
pyridine, intermediate
edta4-, hard
Br-, intermediate
I- soft
243
# Definition
proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetra iron centers in variable oxidation states
Iron sulfur proteins
244
What axial ligands does cytochrome c have?
His and Met
245
Does oxygen bind end-on or side-on to Fe in hemoglobin?
End-on
246
What is known to have a zinc bound to a histidine and two cysteine ligands, as well as an aldehyde?
Dehydrogenase
247
During oxygen transport, the binding of substrate (O2) is accompanied by redox changes, but what happens to the oxidation state?
The overall reaction does not involve a net change in oxidation state
