Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
142 Cards in this Set
- Front
- Back
Cystic Fibrosis |
abnormal secretion in lungs, pancreas, sweat glands; chronic pulmonary disease generally leading to death in children or young adults Effected enzyme or protein: Chloride channel |
|
Lesch-NyhanSyndrome |
Effect: Neurological defects, self-mutilation, mental retardation Effected enzyme or protein: Hypoxanthine-guanine phosphoribosyltransferase |
|
Immunodeficiency Disease |
Effects: Severe loss of immune response Effected protein or enzyme: Purine neucleoside phosphorylase |
|
Immunodeficiency Disease |
Effects: Severe loss of immune response (children must live in a sterile bubble) Effected protein or enzyme: Adenosine deaminase |
|
Gaucher’s Disease |
Effects: Erosion of bones, hip joints; sometimes brain damage Effected protein or enzyme: Glucocerebrosidase |
|
Gout, Primary |
Effects: overproduction of uric acid resulting in recurring attacks of acute arthritis Effected protein or enzyme: Phosphoribosyl pyrophosphate synthetase |
|
Rickets, Vitamin D-dependent |
Effects: short stature, convulsions Effected protein: 25-Hydroxycholecalciferol-1-hydroxylase |
|
Familial Hypercholestrolemia |
effects: Atherosclerosis resulting from elevated cholesterol levels in blood; sometimes early death from heart failure effected protein: low-density lipoprotein receptor |
|
Tay-Sachs Disease |
effects: motor weakness, mental deterioration, often death by age 3 effected protein: Hexosaminidase-A |
|
Sickle-cell Anemia |
effects: pain, swelling in hands and feet; can lead to sudden severe pain in bones or joints and death effected protein: hemoglobin |
|
Most enzymes are ___________ globular proteins which are roughly _____________________ in shape |
soluble spherical or ellipsoidal |
|
The sequence of amino acids in turn determines the folding of the protein and thus its ultimate _________________. Biological function depends on the __________________. |
3D structure 3D structure |
|
Proteins spontaneously fold to place most ________________________ amino acids within the core and most __________________ amino acids on the surface. |
hydrophobic (apolar) hydrophilic (polar) |
|
The process of folding typically follows a hierarchical sequence in which secondary structures involving __________between peptide bond carbonyl (C=O) groups and peptide bond _____________ form first (α-__________________). |
H-bonds amide hydrogens (>N-H) α-helices, parallel and anti-parallel β-pleated sheets |
|
Formation of ____________is followed sequentially by formation of _______________, and then formation of domains and ____________. |
α-helices, parallel and anti-parallel β-pleated sheets super-secondary structures tertiary structures |
|
Association of subunits form _____ |
quaternary structures |
|
Structural proteins, on the other hand, are often __________ with unusual and very stable structures. examples (3) |
very elongated α-Keratin, collagenand elastin |
|
collagen has an unusual _____ |
sequence (X-Y-Gly) |
|
α-Keratin and elastin have ______ |
unusual crosslinks that allow it to stretch without breaking |
|
oxidative damage to an inhibitor of elastin _____ contributes to __________ |
degradation emphasema |
|
Proteins spontaneously fold into a unique three dimensional (3D) structure _________that almost always represents the ________ free energy of all possible folding patterns. |
(native structure) lowest |
|
Each amino acid (except __________) has a carboxyl group, an amino group, and a distinctive side chain (often called the R group) bonded to the ___________. |
(except for proline) α-carbon atom |
|
___________ is the only amino acid without _________ because its alpha-carbon is attached to 2 hydrogen atoms and is therefore not chiral). |
glycine optical activity |
|
chiral amino acids exist in either of _____________termed the D- (dextro; right) and L- (levo; left). The L- and D-enantiomers of an amino acid have ________ chemical properties in all respects except _________ |
two mirror image forms (enantiomers) identical their solutions cause polarized light to rotate in opposite directions. |
|
designations D- and L- refer to the _____________, not to the direction polarized light is rotated (direction of light rotation is denoted in lower case letters: (d) and (l)) |
actual structure |
|
All amino acids (except glycine) found in proteins are of the __________ configuration. |
L-configuration |
|
two broad amino acid classifications |
hydrophilic and hydrophobic amino acids |
|
The distinction is important because |
hydrophillics will be on outside of proteins and hydrophobics will be inside. |
|
nonpolar amino acids proline is an ______________amino acid |
Methionine, Isoleucine, leucine, valine, glycine and alanine MILVGA imino, amino acid |
|
aromatic amino acids |
tryptophan, tyrosine and phenylalanine |
|
The aromatic side chains of these amino acids result in their having characteristic UV absorbance spectra. Consequently, protein concentrations can be estimated by their __________. |
absorbance at 280 nm |
|
The –OH on tyrosine is important because it can be _________________, which are important regulatory enzymes responding to _____________ |
phosphorylated by tyrosine kinases growth factors |
|
Several recently developed cancer drugs___________ are inhibitors of __________ |
[imatinib (Gleevac), sunitinib(Sutent), sorafenib (Nexavar), and several more] tyrosine kinases. |
|
Which absorbs more light at 280 nm wavelength? Put them in order from highest absorbance to lowest. |
tryptophan tryptophan, tyrosine, phenylalanine |
|
hydrophobic polar amino acids can be grouped into _____ subgroups which are _______________ |
two subgroups aromatic and non aromatic |
|
hydrophillic amino acids can be grouped into ____ categories which are _______________ |
two categories uncharged polar and charged polar |
|
Uncharged polar amino acids have ___________ at physiological pH. Met is sometimes classified in this group because of _____________. |
side chains that do not ionize the slightly polar nature of its sulphur-containing side chain |
|
uncharged polar amino acids |
glutamine, asparagine, cysteine, threonine and serine Glu ACTS |
|
Note that the –NH2groups of asparagine and glutamine are ________ and never carry a + charge. Those side-chains are amides, not amines. |
not ionic. Their amid groupd do not have dissociable protons (they are NH2 not NH3+) |
|
Charged polar amino acids have side chains that can carry either a positive charge (the basic amino acids ____________)or a negative charge (the acidic amino acids _______) |
Lys, Arg, and His (+) Asp and Glu (-) |
|
The pKa of a group is the pH at which it is 50% ________ and 50% __________. |
protonated unprotonated |
|
The ratio of protonated (HA) to unpro-tonated (A) forms can be calculated from the Henderson-Hasselbalch Equation: __________. |
pH = pKa+ log[A]/[HA]. |
|
Note that when the pH is _______ than the pKa, the __________; 2 pH units higher and [A]/[HA] is _____. |
one unit higher [A]/[HA] ratio is 10; 100 |
|
at some intermediate pH the amino acid, peptide or protein will have a net charge of zero, this is called the |
isoelectric point |
|
|
titration curve for arginine |
|
pI = _____ |
(pK1+ pK2)/2 |
|
When pKa = pH __________ If you increase by 1 pH unit, you get _________ if you increase pH by 2 pH units, you get _____ What happens if you decrease by 1 unit or 2 units? |
50% prot & 50% unprot 9% prot & 91% unprot 1% prot & 99% unprot The opposite relationship exists, where you increase the protonated species in similar proportions. |
|
methionine and cysteine are the only two amino acids with ______. They have unique______ |
Sulfer sensitivities Sometimes methionine (always the starting amino acid) can become oxidized which impairs its function. |
|
The ______ or sulfhydryl group of cysteine can spontaneously _____ to form a _______two cysteine residues within a protein. When linked cysteine residues are called cystine |
thiol oxidize disulfide bond, linking |
|
Disulfide bonds are important in stabilizing the circulating peptide hormone ____________ |
insulin |
|
Two features of a peptide bond limit the number of conformational states possible for a polypeptide:
|
The strong electronegativity of the carbonyl oxygen relative to the amide nitrogen within the peptide bond and create resonance by delocalizing electrons. & For each peptide bond, the R groups of the two adjacent amino acids could exist in either a cisor transconfiguration |
|
one of the amino acid resonance structures make a double bond character between the C-N- making amino acids _______ about _____ of the time |
planar, with little rotation 40% |
|
the two bonds flanking the alpha-carbon of each amino acid are _________, limited only by possible _________. Their orientations are referred to as __________. |
relatively free to swivel steric hindrance between atoms of the polypeptide chain and R groups phi (; N-C) and psi (; C-C) angles. |
|
he sequence of amino acids in a protein contains all of the information necessary for _______________________ |
it to fold into its final, native 3D shape |
|
What influences protein folding - major one |
1- Hydrophobic forces have a large role in driving folding(i.e., apolar side chains of amino acids associate with each other because their exposure to water is energetically very unfavorable).
|
|
The right-handed alpha helix is a secondary structure. It contains ____residues per turn and is stabilized by hydrogen bonds between the carbonyl and the amide proton of amino acid i+4. The H-bonds are parallel to the helix axis and the amino acid side chains (R groups) project __________ Significant R group steric hindrance destablizes alpha helices having a left-handed screw sense. Alpha helices on the surface of a protein are ______. |
3.6 (5.4 A in height) radially outward, minimizing steric repulsion amphipathic |
|
The beta pleated sheet is distinguished from the α-helix by being stabilized by H-bonds running between _____ parts of the polypeptide chain. Hydrogen bonds are ________ with the beta sheet. _________ alternately project above and below the plane of the sheet. Beta sheets often form ___________ |
carbonyl oxygen atoms and amide protons of non-contiguous co-planar Side chain R groups the hydrophobic core of proteins |
|
The ring structure of ___________ prevents it from forming the H-bonds required for α-helices or β-pleated sheets. So it's found ____________ |
proline where secondary structures end. |
|
Ramachandran was the first to notice the limitation of ________ and plots of favored combinations bear his name. |
psi and phi bonds |
|
secondary structures to make stable associations with one another (e.g., folding over on top of each other). These are called __________ |
super-secondary structures |
|
Domains are the smallest ____________ of protein structure and they often account for a particular part of an ______________ or they may even catalyze one part of a complex reaction sequence. |
thermodynamically stable units enzyme’s active site |
|
Tertiary structure is the term that describes the final thermodynamically stable structure of a single polypeptide chain (___________, then that is the tertiary structure)
|
if there is only one domain |
|
an example of a metamorphic protein is ______ an immunological signaling protein that induces _____________ |
human chemokine lymphotactin, leukocyte migration |
|
Fibrous proteins are characterized by sequences rich in ________ and by regular, repeating secondary structural elements. examples: |
specific amino acids alpha keratin, elastin, collagen |
|
α-Keratin: α-Keratin, the primary component of _________, consists of two ___________ α-helices that are intertwined in a ___________ called an α-coiled coil |
hair an nails right handed left handed super coil |
|
the most abundant protein in the body |
collagen |
|
A typical collagen molecule is a long, rigid structure in which ______________ |
three polypeptides are wound around each other in a rope-like triple helix. |
|
The individual collagen chains (called α-chains) are _______________helices They are wound into a _____________helix |
left handed helices (not alpha helices!!!!) right handed triple |
|
Collagen is rich in _________and each plays an important role in triple helix formation. The ____ stack along the outside of the helix giving it rigidity. __________ having ______ is found at every ________ position of the polypeptide chain so that it can fit into the restricted central space where the three strands come together. |
proline and glycine proline rings glycine Smallest R group 3rd |
|
In X-Y-Gly- the X is often _______ and the Y is often _______________or _____________ |
proline hydroxyproline or hydroxylysine |
|
the two Y molecules are formed after their incorporation into the polypeptide chain and serve to stabilize the triple-helical structure. The enzymes that catalyze the hydroxylation reactions require _______________, a deficiency of which results in __________. |
ascorbate(vitamin C), scurvy |
|
The symptoms of scurvy () are due in part to the decreased _________________. |
bleeding gums tensil strength of their collagen |
|
vitamin c deficiency can have physical ramifications as seen in scurvy (2 examples) |
poor gums easy bruising due to inability to make hydroxyproline and hydroxylysine for collagen. |
|
alcoholics and food fadists in the US sometimes get _________ |
scurvy |
|
after synthesis, post translational modification and triple helix assembly, the almost ready collagen molecule is called ______ before leaving the cell.. Once secreted out, the N and C proterminal peptides are cleaved and its called ________ |
procollagen tropocollagen |
|
___________ is a connective tissue protein with rubber-like properties that is found in ________. |
Elastin the lungs, large arterial walls, and elastic ligaments |
|
Elastin is comprised predominantly of ____________. It's also rich in ________________ NOT___________________ |
small, nonpolar amino acids(e.g., glycine, alanine, and valine) proline and lysine but not hydroxyproline or hydroxylysine. |
|
Elastin precurser |
tropoelastin |
|
In elastin _____________________residues crosslink with ________________ In collagen __________________ residues cross link as well but not as much- it mostly links due to R group interactions |
allysine and lysine allysine and lysine |
|
example of a crosslinked elastin |
desmosine |
|
_____________is a small protein that inhibits a number of proteolytic enzymes in bodily fluids.It inhibits _______________.
|
alpha1-antitrypsin (alpha1-AT) elastase |
|
alpha1-AT (inhibits what inhibits elastin) contains a methionine residue that is essential for binding to target proteins (________). Elements in cigarette smoke cause the oxidation of this Met residue, which renders it unable to bind and inactivate elastase. So cigarette smokers can develop |
elastase emphysema even if they have no mutant α1-AT alleles |
|
|
Oxidants in cigarette smoke convert a methionine residue (left) of α1-AT to methionine sulfoxide (right). With that change α1-AT is no longer an effective inhibitor of elastase. |
|
O2 binding to Hb is cooperative such that binding of each O2 molecule to the tetramer increases the affinity with which tO2binding to Hb is cooperative such that binding of each O2molecule to the tetramer increases the affinity with which the next O2binds__________binds. This is also true for dissociation (the release of one decreases affinity and leads to the release of more) |
the next O2 molecule |
|
The cooperative binding curve greatly supports the release of ___________ into __________ |
O2 into tissues |
|
The affinity of Hb for O2 is decreased by _______ |
H+ (lower pH), CO2, 2,3-diphosphoglycerate (DPG) and increasing temperature (fever) |
|
Sickle cell disease is an inherited mutation of the __________ gene causing a change from _______ to _________________. |
β-globin gene Glu Val at position 6. |
|
Hemoglobin (Hb) is a tetramer comprised of |
2 alpha subunits (from 2 alpha genes) (chromosome 16) and 2 beta subunits from one beta globin gene (chromosome 11 ) |
|
O2 has very ____________ in plasma (the non-cellular part of blood). As a consequence,________of the O2 that reaches tissues is carried in ___________ bound to _____________. |
low solubility >98% reb blood cells hemoglobin |
|
_______________ contain ________________which catalyzes the rapid reversible hydration of _______ to ________ (H2CO3). H2CO3 then rapidly and spontaneously dissociates to __________(HCO3-) and a H+. |
RBCs carbonic anhydrase CO2 carbonic acid bicarbonate |
|
CO2 and, especially, HCO3- are ________ in ________and most of the CO2 made in tissues returns to the ___________ as those species. |
soluble plasma and RBC cytosol lungs |
|
Hb carries more than 98% of O2 where it needs to go but only about ______ percent of CO2 back to the lungs |
14% |
|
The alpha and βsubunits of hemoglobin have similar ___________. Both subunits are evolutionarily related to ________, a monomeric protein abundant in muscle that is designed to store O2 |
sequences and tertiary structures myoglobin |
|
Note that ________is the ________ form of iron that is capable of binding O2; Fe3+ is the _________ form of iron that cannot bind O2and is present in an inactive form of hemoglobin called _______________. |
Fe2+, ferrous ferric methemoglobin FERRICK makes ya sick! ferrous works best |
|
what is significant about this chart |
This chart shows that at pO2 pressures where myoglobin has a high affinity for O2, hemoglobin has a much lower. This is why hemoglobin can release O2 to resting and working tissues. |
|
whats significant |
fetal hemoglobin has a higher affinity for O2 at =PO2 increase PCO2, increase in temp and deccrease in pH lowers Hb affinity for O2 *shifting the curve to right. |
|
Carbon monoxide (CO) has a much higher affinity for Hb than does O2. When bound to the heme group of one subunit, it causes all four subunits to “lock”in the R conformation. What effect would this have on O2delivery? |
This would cause the R locked heme groups to hold on tight to their O2 and not release it in the tissues. |
|
Metabolically active tissues need more _______; they generate more __________ which causes hemoglobin to release its O2 |
O2 CO2 and H+ |
|
2,3-Bisphosphoglycerate is a negative effector. • A single 2,3-BPG binds to a _____________ and stabilizes it by interacting with __________. |
a central pocket of deoxyhemoglobin three positively charged aa of each β-chain |
|
Fetal hemoglobin has 2 α and 2 chains |
γ |
|
The binding affinity of fetal hemoglobin for _________ is significantly lower than that of adult hemoglobin |
2,3-BPG |
|
Without O2 bound, the heme Fe2+ is __________ the plane of the ___________ by a _______ residue of the Hb polypeptide chain (a His ring N is bound to the Fe2+). When O2 binds, it ________ the plane of the ring and that moves ___________ and its whole section of the polypeptide chain. |
pulled away from, porphyrin ring, His pulls the Fe2+ back into the His residue |
|
DPG--HHb--CO2 +O2 <--->?
|
HbO2 + CO2 + DPG + H+
That is, protons (H+), CO2, and 2,3-diphosphoglycerate (DPG) ALL can bind to Hb and reduce its affinity for O2(i.e., if CO2, H+and DPG are high, the equilibrium shown is driven to the left and O2comes off Hb). Correspondingly, if O2is high, then the equilibrium is driven to the right and H+and CO2and DPG will dissociate from Hb as O2binds |
|
H+and CO2are ________________effectors that decrease the affinity of ______ for O2. They are heterotropic because they __________; negative because they decrease affinity for O2; and allosteric because they bind to a site other than the O2site(s) affected. |
heterotropic negative allosteric Hb are not O2 |
|
The reciprocal relationship between O2 and H+ binding is termed the Bohr effect or ________ |
isohydric shift. |
|
Changes in H+ binding result from a shift in the ______________ due to microenvironment effectstriggered by ________________. |
pKa of specific residues (mostly histidines) conformational changes in the hemoglobin molecule |
|
2,3-DPG binds to a specific site in a central cavity between the_________. |
βsubunits. |
|
lots of _______________ charges on 2,3-DPG allow it to bind to __________________________. |
negative positively charged groups of Hbβ-chains |
|
There are 2 important things to notice about the effect of 2,3-DPG on the O2 binding curves shown in the figure. First, ______________, Hb would be much more like myoglobin and nearly useless for delivering O2 from lungs to tissues. 2,3-DPG stabilizes _________-state, making it easier for Hb to release O2. Second, 2,3-DPG levels increase at high altitudes. |
without any 2,3-DPG, the T |
|
Hemoglobin Milwaukee (Hb M) is a rare dominant mutation of the β-subunit (Glu replaces Val at amino acid _________). The change allows the Fe to be more easily oxidized and affected patients have high levels of MetHb (15-30%). Few consequences in everyday life. |
67 |
|
Hemoglobin is caused by a point mutation in the adult β-globin gene that causes substitution of valine (Val) for glutamic acid (Glu) at amino acid ____. So patients RBCs containing mainly________, which is comprised of two normal adult alpha-globin subunits and two ______ subunits. The amino acid at position 6 is on the surface of the β-chain and it should be a ____. Valine is _____ and its presence creates a sticky patch on deoxyHbthat leads to polymerization of Hb tetramers into long chains. |
6 hemoglobin S (HbS) sickle adult β-globin hydrophilic amino acid (Glu is) hydrophobic |
|
what structural changes lead to a shorter erythrocyte half-life and chronic hemolytic anemia?
|
The replacement of val by Glutamine (nonpolar) makes the surface of beta globin chain sticky and cause a fibers and the erythrocyte to sickle- this leads to.... |
|
A critical contact is made by the β6 VAL of one molecule and a hydrophobic acceptor pocket of the βsubunit of another molecule formed by Leu88 and Phe85 surrounded by hydrophilic residues. The presence of a __________________in HbA prevents this interaction.
|
charged amino acid (Glu) |
|
___________________ HbS forms insoluble polymers]
|
Deoxygenated |
|
__________ inhibits polymerization owing to a GLU residue at position 87 of the __________, which prevents a critical lateral contact in the sickle cell fiber. HbF decreases with post-partum age but varies from ______ of total Hb in sickle cell individuals. |
HbF gamma chain 1-30% |
|
Sickling leads to Membrane Distortion leads to Ca2+-leakage The Gardos Effect: increased intracellular Ca2+activates the Gardos channel leads to export of K+ Loss of _____________ leads to dehydration leads to [HbS] |
K+, Cl-and H2O |
|
_________________, an antitumor drug, is currently the only drug in widespread use for the treatment of sickle cell anemia. It stimulates _______production.
|
Hydoxyurea fetal hemoglobin |
|
an imbalance in the concentration of alpha -globin or β-globin chains
|
Thalassemias |
|
alpha thalassemia is normally asymptomatic. beta thalesemias can affect _________ |
chain termination, transcription activation, and RNA processing. |
|
substituting Lys for glutamine at position 6 on the b globin gene creates the ______ allele which is found with the __________allele causing _____________ in patients |
HbC HbS HB Sc disease ( a milder form of sickle cell) |
|
only difference betwen thymine and uracil is only difference between cytosine and uracil is |
Thymine has a methyl group at on C5 cytosine has nh2 coming from c 4 position instead of a double bonded O like thymine and uracil |
|
deoxyribose and ribose differ at _______ |
C2 |
|
The antibiotic ______________ (produced by Streptomyces antibioticus) binds to DNA duplexes, thereby interfering with the action of enzymes engaged in replication and transcription. It is an anti-cancer drug commonly used in the treatment of pediatric malignancies such as_______________________ |
actinomycin D Wilms' tumour, Ewing's sarcoma and rhabdomyosarcoma |
|
Two helical polynucleotide chains coiled around a common axis that run in __________ directions, resembles a twisted ladder structure |
antiparallel |
|
The planes of the DNA bases are“stacked” _____________ to the helix axis. ______________ helps stabilize double helix. |
perpendicular Stacking resonance |
|
DNA Helical structure repeats after ______ residues at intervals of ______ angstroms. |
10.5 36 |
|
N------O bond length between nitrogenous bases is ALWAYS _______ |
Spacing constant: 2.9 A |
|
DNA melting can be monitored spectrophotometrically at 260 nm due to a ___________ that occurs upon base stacking annealed DNA
|
hyperchromic shift |
|
DNA molecules can be______________.Linear and circular DNA have very different topological properties. |
linear, relaxed circular, or supercoiled circular |
|
Positive supercoiling of DNA occurs when the right-handed, double-helical conformation of DNA is twisted even tighter (twisted in a right-handed fashion). Negative supercoiling, on the other hand, involves twisting against the helical conformation (twisting in a left-handed fashion), which preferentially underwinds the helix at low twisting stress, and knots the DNA into negative supercoils at high twisting stress. Negative supercoils favor ____________________
|
local unwinding of the DNA, allowing processes such as transcription, replication and recombination-DNA in cells is typically somewhat negatively supercoiled.
|
|
topoisomerases type 1s : ATP independent |
1) cleaving one strand of DNA
2) passing a segment of DNA through the break 3) resealing the break. 4) DO NOT need energy donors (ie, ATP-independent) |
|
type 2 topoisomerases (ATP needed): |
1) two strands are cleaved2) the DNA is passed through the break3) the break is resealed.
|
|
chromatin condensation is associated with |
phosphorylation |
|
Actinomycin D is |
An anticancer drug that intercelates with the minor groove of DNA to interfere with its transcription and translation |
|
Uracil and cytosine differ at the ____ position. There, cytosine has a substituted amid group instead of a _________ |
4' position Double bonded oxygen |
|
Uracil and thymine differ at the ____position. There, thymine gas ________ instead of just a hydrogen like uracil has. |
5' position Methyl group |
|
Adenine and Gaunine differ in two places, at 2'(bottom left) and _______(top of the six membered ring). At the 2' guanine has an amid branch, Adenine has a hydrogen. At the top of the six mbrd ring, Adenine has _________ and Gaunine has a _____. |
6' position An amid Double bond O |
|
The major groove of the RH B form of DNA is _______ angstrums. The minor is _______ |
12 Half @ 6 angstrums |
|
Streptomyces antibioticus makes ______ |
Actinomycin. An anti cancer drug that binds minor DNA groove and interferes with replcation and transcription enzyme action |
|
Used in treatment if wilms tumor, Ewing sarcoma and rhabdomyosarcoma |
Actinomycin D |
|
The nucleotide rings are aligned ________ the phosphate backbone |
Perpendicular ....this is why there is "stacking resonance" in intact dna |
|
Assembly of preinitation complex (closed process) is the _________ of transcriptional initiation and transcription. |
Rate determination step |