Exam 3 Biochem 351 Norcio

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Some Common Protein Functions

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Enzymatic catalysis – enhances reaction rates by at least a million fold. All known enzymes are proteins. (Chap. 6) Transport and storage – many small molecules and ions are transported by specific proteins. For example, hemoglobin transport oxygen in erythrocytes, while myoglobin, transports oxygen in muscles. (Chap. 5) Coordinated motion – proteins are the major component of muscle. Muscle contraction is accomplished by the sliding motion of 2 kinds of protein filaments. (Chap. 5) Mechanical support – the high tensile strength of skin and bone is due to the presence of collagen, a fibrous protein. (Chap. 4) Immune protection – antibodies are highly specific proteins that recognize and combine with foreign substances as viruses, bacteria, and cells from other organisms. (Chap. 5) Generation and transmission of nerve impulses – the response of nerve cells to specific stimuli is mediated by receptor proteins. (Ch. 12) Control of growth and differentiation – proteins are important control elements that signal or silence specific segments of the DNA of a cell.(Ch. 8)

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Reversible, transient process of chemical equilibrium

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A + B <--> AB

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A molecule that binds to a protein. typically a small molecule

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ligand

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A region in the protein where the ligand binds

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binding site

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Ligand binds via same ______ that dictate protein structure. Allows the interactions to be transient

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noncovalent forces

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Noncovalent forces allow the interactions to be what?

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transient

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Consider a process in which a ligand (L) binds reversibly to a site in a protein (P)

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binding: quantitative example

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Equilibrium association constant

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Ka

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When ligand is a gas, binding is expressed in terms of?

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partial pressures--->

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The fraction of bound sites depends on?

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free ligand concentration [L] and Kd

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what can be done experimentally for binding?

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Ligand concentration is known, Kd can be determined graphically or via least-squares regression

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Globins are?

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oxygen-binding proteins

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Protein side chains

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lack affinity for O2

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Some transition metals bind O2 well but would generate free radicals if

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free in solution

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Organometallic compounds such as ___ are more suitable, but Fe2+ in free ____ (with two open coordination bonds) could be oxidized to Fe3+

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heme, heme

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solution to free radicals:

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Capture the oxygen molecule with the heme that is bound deep into the protein structure where access to the two open coordination bonds is restricted.

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The protein ____ (Mr of 16,700) is a single polypeptide of 153 AA residues with one molecule of a heme.____ is the oxygen-binding protein found in almost all mammals, primarily in muscle tissue.It is a storage protein and facilitates oxygen diffusion in the muscle.

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myoglobin

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present in myoglobin, hemoglobin, and many other proteins

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heme groups

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Heme consists of a complex organic ring called _____ to which an iron atom in its ferrous (Fe2+) state is bound

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protoporphyrin IX

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The iron atom has

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six coordination bonds, four to nitrogen atoms that are part of the flat porphyrin ring system and two perpendicular to the porphyrin.

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The coordinated nitrogen atoms prevent the...

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conversion of Fe2+ to Fe3+. Oxygen does not bind to iron in the Fe3+ state.

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When oxygen binds,

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the color changes form dark purple to bright red.

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The proximal histidine (F8) is pulled along with the Fe2+ and becomes

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less titled.

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CO and NO

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bind to the heme site with greater affinity than oxygen ---> toxic.

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_______ binds 25,000 times more tightly than O2 to free heme, but only 200 times more tightly to myo(hemo)globin. This occurs because the ______ forces CO and O2 to bind at a 120° angle, preferentially weakening CO binding.

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Carbon monoxide , "distal" histidine (His E7)

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Oxygen is carried by ____ in red blood cells_____ is a tetrameric protein.Each subunit of _____ has a heme.

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hemoglobin

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_____ in the bone marrow give rise to all the different types of blood cells.

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Hemocytoblasts (stem cells)

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Hemoglobin is composed of

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four globular domains arranged in a tetrahedron. There are 2 a chains and 2 b chains. Although over half of the amino acids in the a and b chain polypeptide sequences are different, the three dimensional structures are very similar.Both a and b are structurally similar to myoglobin although their sequences are only ~17% identical.

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The quaternary structure of hemoglobin features

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strong interactions between unlike subunits.

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Experimental evidence: _____ dimers are strong enough to survive mild treatment of urea denaturation.

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a1b1 and a2b2

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There is a ____ between a and b subunits (a are light and b are dark).

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strong interaction

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The T-state is stabilized by a greater number of ____ , many of which reside at the a1b2 and a2b1 interface

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salt bridges

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More interactions, more stable Lower affinity for O2

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T = Tense state,

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Fewer interactions, more flexibleHigher affinity for O2

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R = Relaxed state,

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In the _____, the porphyrin is slightly puckered causing the heme Fe2+ to protrude on the His F8.

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T state

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Conformational change from the T state to the R state involves _____ between the α1-b2 interface

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breaking ion pairs

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States of hemoglobin

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tense and relaxed

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Conformational change is triggered by

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oxygen binding

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The binding of O2 causes the heme to assume a more _____configuration shifting the position of His F8 and the attached F helix. These shifts result in changes throughout hemoglobin.

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planar

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pO2 in lungs is about 13 kPa:

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it sure binds oxygen well

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pO2 in tissues is about 4 kPa:

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it will not release it!

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Protein must have

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multiple binding sites

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Binding sites must be able to

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interact with each other

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first binding event increases affinity at remaining sitesrecognized by sigmoidal binding curves

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positive cooperativity

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first binding event reduces affinity at remaining sites

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negative cooperativity

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Oxygen binding to individual subunits of hemoglobin will alter the affinity of oxygen in adjacent units.1st O2 binding is difficult since hemoglobin is in stable T state.

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Cooperative

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Oxygen binding to myglobin is independent and cannot affect the binding of other oxygen molecules.

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noncooperative

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Cooperativity is a special case of

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allosteric regulation

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Allosteric regulation is....

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Binding of a ligand to one site affects the binding properties of a different site, on the same proteinCan be positive or negative regulation

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When the normal ligand of the protein and the allosteric regulator are identical

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Homotropic

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When the regulator protein is a molecule other than the normal ligand

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Heterotropic

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Cooperativity is a

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positive homotropic regulation.

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The Bohr Effect is

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the shift of reaction due to changes in [H+]and [CO2]. Effectors: H+ and CO2

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↑ pH or ↓[H+]:

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favors oxygenated form; curve becomes less sigmoidal

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↓ pH or ↑[H+]:

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favors deoxygenated form; curve becomes more sigmoidal

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In aerobic metabolism, ____ are generated per mole of O2 consumed.

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~ 0.8 moles of CO2

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Although CO2 is ultimately expired from the ____, it cannot be transported in the blood as a dissolved gas due to limited solubility.

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lungs

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Hemoglobin acts directly in CO2 transfer to the lungs via reversible binding to the α-amino groups of the protein to form _____.

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carbamates

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In tissues, ↑[CO2]:

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favors deoxygenated form and release of O2

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In the lungs ↑[O2]=98% saturation:

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favors oxygenated form

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Oxygen binding to hemoglobin is regulated by?

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2,3-bisphosphoglycerate (BPG).

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BPG is _________

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highly negatively-charged molecule

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In the ______, the hole becomes larger. BPG sneaks in the hole, binds and stabilizes the deoxygenated form.

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deoxygenated form of hemoglobin

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At _____, BPG is squeezed out. Hemoglobin can bind with O2 once again.

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high pO2

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BPG binds to the _______ of hemoglobin

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central cavity

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Fetus has ______ (α2γ2) while the adult has _____ (α2β2).

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hemoglobin F, hemoglobin A

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Hemoglobin F has _____ than hemoglobin A.

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higher oxygen affinity

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Hemoglobin F is ______on the other side of the placental circulation.

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oxygenated at the expense of hemoglobin A

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Hemoglobin F has _____ to BPG than does hemoglobin A.

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less affinity

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What are the functional differences of hemoglobin compared to myoglobin?

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In hemoglobin:1) binding one O2 molecule enhances the binding of additional O2 (cooperative binding);2) O2 binding is dependent on CO2, H+ (Bohr Effect);3) O2 binding is regulated by BPG.

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Two Types of Immune Systems

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Cellular immune system, Humoral “fluid” immune system

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targets own cells that have been infectedalso clears up virus particles and infecting bacteriakey players:, cytotoxic (or killer) T cells (Tc), and helper T cells (TH), Class I MHC proteins

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Cellular immune system

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targets extracellular pathogenscan also recognize foreign proteinsB-cells make soluble antibodies keeps “memory” of past infectionskey players: Macrophages, B-lymphocytes (B-cells) and helper T-cells (TH), Class II MHC proteins

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Humoral “fluid” immune system

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macrophages

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ingest large particles and cells by phagocytosis

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B lymphocytes (B cells) and T lymphocytes (T cells)

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produce and secrete antibodies

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Cytoxic (killer) T cells (Tc)

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interact with infected host cells through receptors on T cell surface

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Helper T cells (Th)

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interact with macrophages and secrete cytokines (interleukins) that stimulate Tc, Th, and B cells to proliferate.

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– are proteins involved in the recognition of infected cells or parasites. They are located on the surface of the T cells.

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T cell receptors

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– is any molecule or pathogen (MW > 5000) capable of eliciting an immune response. It can be a virus, bacterial cell wall, a protein, or other macromolecules.

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Antigen

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– a particular molecular structure within the antigen where an antibody or T-cell receptor binds.

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Epitope or antigenic determinant

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– small molecules (MW<5000) that can be covalently attached to large proteins in the laboratory. In this form, they may elicit an immune response.

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Haptens

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Detection of protein antigens in a host is mediated by______ .

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Major Histocompatibility Complex proteins or MHC's

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MHC proteins bind ______ of proteins digested in the cell and present them on the outside surface of the cell.

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peptide fragments

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Peptide fragments from foreign proteins that are displayed by MHC proteins are the antigens the immune system recognizes as _____.

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nonself

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______bind and display peptides derived from the degradation of proteins that occurs within the cell.

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Class I MHC proteins

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These complexes of peptides derived from the degradation of proteins are the recognition targets of the T cell receptors of the Tc cells in the ______.

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cellular immune system

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Class 1 MHC proteins Stimulate Tc cells to _____ .

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destroy infected cells

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Class I MHC proteins are found in virtually all _____.

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vertebrate cells

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______ are found on surfaces of a few types of specialized cells, including macrophages and B cells that take up foreign antigens.Activates Tc and B cells via helper T cells to generate antibodies.

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Class II MHC proteins

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Class II MHC proteins bind and display peptides derived not from cellular proteins but from _____.

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external proteins

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– found principally in secretions such as saliva, tears, and milk. It can be a monomer, dimer or trimer.

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IgA

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– function is not clear. (structure same as IgG)

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IgD

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– plays an important role in the allergic response. (structure same as IgG)

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IgE

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– the major antibody in secondary immune responses, initiated by B cells. Most abundant immunoglobulin in the blood.

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IgG

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– the major antibody in the early stages of a primary immune response.

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IgM

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Immunoglobulin G

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Composed of two heavy chains and two light chainsComposed of constant domains and variable domains

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one constant and one variable domain

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Light chains:

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three constant and one variable domain

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Heavy chains:

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________ of each chain make up antigen- binding site (two/antibody).contain regions that are hypervariable (specifically the antigen-binding site)Confers high antigen specificity

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Variable Domains

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To generate an optimal fit for the antigen, the binding sites of IgG often undergo _____

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slight conformational changes (induced fit model).

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Once the IgG antibody has bound to the antigen it then binds to the IgG Fc receptor on a macrophage which then ______.

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destroys the antigen

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Use of ______ can cause conformational changes in proteins, generally required for their function.Especially in motor proteins:(4 things)

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chemical energy (ATP), contraction of muscles,migration of organelles,rotation of bacterial flagella,movement of proteins along the DNA

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large, single, elongated, multinuclear cell Each fiber contains about 1,000 myofibrils

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Muscle fiber:

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– a bipolar structure formed from myosin aggregates

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Thick filament

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Myosin has two ______ and four ______.

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heavy chains (two shades of pink), light chains (two shades of blue)

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Each heavy chain has a large globular domain containing a ______.

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hydrolysis site for ATP

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The heavy chains are wrapped around each other in a _____.

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left-handed coiled coil

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Monomers of G-actin associate to form a long polymer called ______.The thin filament consists of _______.

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F-actin , F-actin (troponin and tropomyosin)

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Myosin thick filaments ____ actin thin filaments

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slide along

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Muscle contraction is regulated by ____

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troponin and tropomyosin

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_____ binds to thin filament and blocks attachment of myosin head groups.

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Tropomyosin

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When a nerve impulse is received, it causes the release of Ca2+ from the ______ .

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sacroplasmic reticulum

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______is a Ca2+-binding protein. Once bound to Ca2+, it causes conformational changes, exposing myosin-binding sites on thin filaments and contraction follows.

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Troponin

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Enzymes are _____ for biological reactions. _____ increase reaction rates without being used up

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catalysts

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Most enzymes are_______However, some RNA (ribozymes and ribosomal RNA) also catalyze reactions

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globular proteins

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– a pocket in an enzyme with the specific shape and chemical makeup necessary to bind a substrate.

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Active site

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– a reactant in an enzyme-catalyzed reaction.

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Substrate

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Some enzymes require additional chemical groups for activityAdditional components:

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Cofactor, coenzyme

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– inorganic ion such as Fe2+, Mg2+, Zn2+.

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Cofactor

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– a complex organic or metallo-organic molecule that acts as transient carriers of specific functional groups

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Coenzyme

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– a complete, catalytically active enzyme together with its bound coenzyme or cofactor.

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Holoenzyme

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– the protein part of a holoenzyme.

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Apoenzyme or apoprotein

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Enzymes are classified by?

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the reactions they catalyze.

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Enzymes have the family-name ending in ____.

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-ase

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Exceptions occur for enzymes such as ____ and _______, which are still referred to by older common names rather than ending in ase.

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papain, trypsin

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Modern systematic names always have two parts: ?????Example: Pyruvate carboxylase is a ligase that acts on the substrate pyruvate to add a carboxyl group.

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substrate on which the enzyme operates, enzyme subclass

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– catalyze redox reactions of substrates, most commonly addition or removal of oxygen or hydrogen. These enzymes require coenzymes that are reduced or oxidized as the substrate is oxidized or reduced

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Oxidoreductases

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Enzyme classification: (6 things)

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Oxidoreductases, Transferases, Hydrolases, Ligases, Isomerases, Lyases

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- catalyze transfer of a group from one molecule to another. Kinases transfer a phosphate group from ATP to give ADP and a phosphorylated product.

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Transferases

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- catalyze the breaking of bonds with addition of water. The digestion of carbohydrates and proteins by hydrolysis requires these enzymes

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Hydrolases

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- catalyze the bonding together of two substrates. Such reactions are generally not favorable and require energy from ATP hydrolysis.

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Ligases

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-catalyze the isomerization (rearrangement of atoms) of a substrate in reactions that have but one substrate and one product.

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Isomerases

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-catalyze the addition of a molecule to a double bond or the reverse reaction in which a molecule is eliminated from a double bond.

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Lyases

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Two models are invoked to represent the interaction between substrates and enzymes. Historically, the_______ model came first. The substrate is described as fitting into the active site as a key fits into a lock (specificity). Enzyme molecules are not totally rigid like locks. The _______ accounts for changes in the shape of the enzyme active site that accommodate the substrate and facilitate the reaction.

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lock-and-key, induced-fit model

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As an ___ ____ come together, their interaction induces exactly the right fit for catalysis of the reaction.

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enzyme and substrate

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Enzymes affect reaction rate (k), but not ____ or _____

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equilibria (Keq), delta G

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a catalyst can only affect ____proportionally, therefore a catalyst cannot affect K'eq

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kf and kr

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A large negative ΔG does not mean that the reaction will proceed at a rapid rate.Slow reactions face significant barrier called _____ that must be surmounted during the reaction.

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activation energy (ΔG‡)

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Enzymes increase reaction rates (k) by____ ?

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decreasing ΔG‡

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k and ΔG‡ have an _____ relationship

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inverse and exponential

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The rate of any reaction is also affected by ____?

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concentration of reactant (substrate), temperature, and pressure.

Front 142

Thermodynamic and Physical Factors contributing to ΔG‡ (the barrier to reaction):

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Entropy reduction (-ΔS), Solvation shell of H-bonded water which surrounds and stabilizes biomolecules in aqueous solution (-ΔS), Distortion of substrates that must occur in many reactions, The need for proper alignment of catalytic functional groups on the enzyme

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Enzymes ____ ΔG‡

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Lower

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How Do Enzymes Lower ΔG‡?

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Catalytic enzymes are not consumed during a biochemical reaction.Formation of weak interactions in the E-S complex is accompanied by release of free energy called binding energy, GB.This binding energy is a major source of free energy used by enzymes to lower the activation energies of reactions.

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Once a substrate is bound to an enzyme, a variety of mechanisms aid in the cleavage and formation of bonds.These catalytic mechanisms are distinct from binding energy because they generally involve the formation of transient covalent interactions.What are these mechanisms?

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I. Acid-base catalysis II. Covalent catalysis III. Metal ion catalysis

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The formation of unstable charged intermediates tends to break down rapidly to their reactant species.Charged species are often stabilized by the transfer of protons to form products more readily.

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Acid-Base Catalysis

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– uses only the H+ or OH- ions present in water.In some cases, water is not enough to stabilize the intermediate.

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Specific acid-base catalysis

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– uses proton transfers mediated by weak acids and bases other than water.

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General acid-base catalysis

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A transient covalent bond between the enzyme and the substrate.Changes the reaction Pathway.Requires a nucleophile on the enzyme. Can be a reactive serine, thiolate, amine, or carboxylate

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Covalent Catalysis

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Involves a metal ion bound to the enzyme or metals taken up from solution along with the substrate

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Metal Ion Catalysis

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(1) Interacts with substrate to facilitate binding Stabilizes negative charges (2)Participates in oxidation-reduction reactions by reversible changes in the metal ion’s oxidation state

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Modes of Action for metal ion catalysis:

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______ uses most of the enzymatic mechanisms

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Chymotrypsin

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Chymotrypsin Mechanism

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Step 1: Substrate Binding

Step 2: Nucleophilic Attack
Step 3: Substrate Cleavage
Step 4: Water Comes In
Step 5: Water Attacks
Step 6: Break-off from the Enzyme
Step 7: Product Dissociates

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-affects the rate of enzyme-catalyzed reactions. (It is 5 to 6 times greater than [E] in a typical reaction)

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Substrate concentration, [S]

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The problem is that [S] diminishes as the reaction proceeds
The solution is to monitor first _____ or less of reaction. Changes in [S] is negligible or [S] is held constant.

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60 seconds

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Kinetic Measurements experiment:

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1) Mix enzyme + substrate
2) Record rate of substrate disappearance/product formation as a function of time (the velocity of reaction)
3) Plot initial velocity versus substrate concentration.
4) Change substrate concentration and repeat

Front 157

Effect of substrate concentration

ideal rate: Vo= (Vmax [S])/(Km + [S])

deviations due to:

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limitation of measurements,
inhibitors

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Enzyme Kinetics with One Substrate:

Simplest model:

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one reactant,
one product,
no inhibitors

Front 159

Enzyme saturation

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– enzymes are saturated with substrate

Front 160

Enzyme Kinetics with One Substrate Assumptions:

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1) Enzyme saturation

2) Total enzyme concentration is constant.

3) Steady state

4) k-2 is ignored

Front 161

Km

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(Michaelis constant): can be an approximate measure of substrate’s affinity for enzyme

Front 162

______- (maximum velocity that an enzyme can achieve) is dependent on [Et]

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Vmax

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Michaelis-Menten Equation

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Vo= (Vmax[S])/(Km + [S])

Front 164

= initial rate

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Vo

Front 165

At ______, the reaction rate is directly proportional to the substrate concentration.

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low substrate concentration

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With increasing substrate concentration, the rate drops off as ______?

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more of the active sites are occupied.

Front 167

With all active sites occupied, the rate_____?

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reaches a maximum.

Front 168

kcat (turnover number):

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how many substrate molecules can one enzyme molecule convert to products per second

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Km cannot be a ______?

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simple measure of substrate affinity. Km becomes a function of many rate constants.

Front 170

Diffusion limit

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– rate at which E and S can diffuse together in an aqueous solution

Front 171

Compare catalase vs. acetylcholinesterase

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Compare catalase vs. acetylcholinesterase is in the notes

Front 172

How closely kcat/Km approaches the diffusion limit is a measure of ____?

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the kinetic perfection of an enzyme.

Front 173

When two or more reactants are involved, enzyme kinetics will allow us to distinguish between different kinetic mechanisms like:

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Sequential mechanism
Ping-Pong mechanism

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Sequential Kinetic Mechanism:

Intersecting lines indicate that a _____?

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ternary complex is formed

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Parallel lines indicate a_____?

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Ping-Pong pathway

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-molecular agents that interfere with catalysis, slowing or halting enzymatic reactions.

They are among the most important pharmaceutical agents known.
Ex. Aspirin inhibits the enzyme that catalyzes the first step in the synthesis of prostaglandins (also involve in producing pain).

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Enzyme inhibitors

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Competitive Inhibition

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Competes with substrate for binding
Inhibitor binds to the active site
Enzyme efficiency is reduced

No change in Vmax; apparent increase in KM

Lineweaver-Burk: lines intersect at the y-axis

Not an efficient enzyme since inhibitor is interfering

Slope increases with [I] --> Km also increases by a factor of α.

Addition of the inhibitor decreases the velocity but not the Vmax. The apparent Km is higher in the presence of inhibitor.
Sufficiently high [S] will saturate the active site so that Vmax is not affected.

Front 178

I. Reversible inhibition
(1) competitive inhibition
(2) uncompetitive inhibition
(3) mixed inhibition
II. Irreversible inhibition

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2 types of inhibition with their subtypes?

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Uncompetitive Inhibition

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Inhibitor only binds to ES complex
Does not affect substrate binding

Lineweaver-Burk: lines are parallel and

constant slope(Km/Vmax), but varying y-intercept
increasing [I] decreases Vmax and Km

Increasing [S] will not increase Vmax as long as inhibitor is present.

Front 180

Mixed Inhibition

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Binds enzyme with or without substrate
Inhibitor binds to a regulatory site
Lineweaver-Burk: lines intersect left from the y-axis

Vmax decreases as [I] increases. Km increases as [I] increases.

Front 181

Noncompetitive inhibitors are mixed inhibitors such that there is ____?

Back 181

no change in Km when α=α’

Front 182

Noncompetitive inhibitors (α = α’)

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Vmax decreases as [I] increases. Km is usually not affected.

Front 183

effects of reversible inhibitors on apparent Vmax and apparent Km: None:

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Apparent Vmax: Vmax

Apparent Km: Km

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effects of reversible inhibitors on apparent Vmax and apparent Km: Competitive:

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Apparent Vmax: Vmax

Apparent Km: αKm

Front 185

effects of reversible inhibitors on apparent Vmax and apparent Km: Uncompetitive:

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Apparent Vmax: Vmax/α'

Apparent Km: Km/α'

Front 186

effects of reversible inhibitors on apparent Vmax and apparent Km: Mixed:

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Apparent Vmax: Vmax/α'

Apparent Km: αKm/α'

Front 187

Irreversible inhibition

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– the inhibitor remains permanently bound and the enzyme is permanently inhibited. Many irreversible inhibitors are poisons.

Ex. Parathion, malathion (organophosphorus insecticides) and nerve gases are irreversible inhibitors of acetylcholinesterase.

Front 188

Enzyme catalytic activity is highly dependent on _____.

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pH and temperature

Front 189

Effect of Temperature and pH on Enzyme Activity:

Optimum conditions vary slightly for each enzyme but are generally near ____?

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normal body temperature and the pH of the body fluid in which the enzyme functions.

Front 190

Effect of Temperature and pH on Enzyme Activity:

Pepsin, which initiates _____, has its optimum activity at pH __.

Back 190

protein digestion in the highly acidic environment of the stomach,

2

Front 191

Effect of Temperature and pH on Enzyme Activity:

Trypsin, which acts in the _____, has optimum activity at pH ___.

Back 191

alkaline environment of the small intestine,

8

Front 192

The rate increases with increasing temperature until the protein begins to _____; then the rate decreases rapidly. The optimum activity for an enzyme occurs at the_____.

Back 192

denature

pH where it acts

Front 193

Regulatory enzymes

Back 193

-exhibit increased or decreased catalytic activity in response to certain signals.

Front 194

Regulation is important because it _____?

Back 194

saves energy to produce unneeded products and diverts to the production of other needed metabolites.

Front 195

The activities of regulatory enzymes are modulated:

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(a) reversible and non-covalent modification: allosteric modulators (effectors)
(b) reversible, covalent modification
(c) irreversible proteolytic cleavage

Front 196

Allosteric control:

Back 196

An interaction in which the binding of a modulator at one site on a protein affects the protein’s ability to bind another molecule at a different site.

Front 197

The modulator maybe _____?

Back 197

inhibitory (negative) or stimulatory (positive).

Front 198

Allosteric modulators are different from uncompetitive and mixed inhibitors. The latter do not _____?

Back 198

mediate conformational changes between active and inactive forms.

Front 199

Binding a ______ changes the active sites so that the enzyme becomes a better catalyst and the rate accelerates.

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positive regulator

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Binding a ______ changes the active sites so that the enzyme is a less effective catalyst and the rate slows down.

Back 200

negative regulator

Front 201

Feedback inhibition

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-the regulatory enzyme (an allosteric enzyme) is inhibited by the end product of the pathway.

Front 202

Allosteric enzyme kinetics differ from ____?

Back 202

Michaelis-Menten kinetics.

Front 203

Allosteric enzyme plots of vo vs [S] usually produce ___?

Back 203

sigmoidal saturation curves

Front 204

Sigmoidal curves generally reflects ____?

Back 204

cooperative interactions between multiple subunits

Front 205

Effects of positive and negative modulation on an allosteric enzyme show changes in K0.5.
Positive effect:

Back 205

more hyperbolic

Front 206

Effects of positive and negative modulation on an allosteric enzyme show changes in K0.5.
Negative effect:

Back 206

more sigmoid

Front 207

The least common type of modulation:

Back 207

K0.5 is constant and Vmax is altered.

Front 208

Irreversible Proteolytic Cleavage:

Back 208

Some enzymes are synthesized in inactive forms known as zymogens or proenzymes, activation requires a chemical reaction that splits off part of the molecule.
Example: chymotrypsin and trypsin (digestive enzymes in the small intestine) are initially synthesized as chymotrypsinogen and trypsinogen in the pancreas. They are inactive when synthesized so that they do not immediately digest the pancreas.

Front 209

Enzymes that cause blood clotting or digest proteins are examples of enzymes that ____?

Back 209

must not be active at the time and place of their synthesis

Front 210

Fibrinogen is a ____?

Back 210

dimer of heterotrimers (α2β2γ2).
It is converted to fibrin (activated for blood clotting) by the removal of 16 amino acid residues from the amino terminal of each α subunit and 14 amino acid residues from the amino terminal of each β subunit.

Front 211

A blood clot consists of _____, tied together with strands of cross-linked fibrin.

Back 211

aggregated platelets (light-colored cells)