Term
Animal Cell vs. Bacterial Cell
(size, components) |
|
Definition
Animal:
Approx. 10 - 50 micrometers long
Membrane-bound organelles
Nuclear membrane/nucleus
CATABOLIC and METABOLIC reactions can be selectively partitioned
Bacteria:
About 1 micrometer long (mycoplasma are even smaller - 3 micron)
No organelles
Nucleoid
ALL METABOLISM occurs in the cytosol
Both contain RNA (smaller in bacteria/archae)
-enzymes that perform protein synthesis |
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Term
|
Definition
Diffusion rate - must be SMALL enough for rapid diffusion
Components - must be LARGE enough for full set of components |
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Term
|
Definition
Overcrowded, very little bulk water
-Leads to weak MACROMOLECULAR interactions |
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Term
|
Definition
Most have DOUBLE membrane
-Outer membrane allows passage
-Inner membrane selectively soluble
Nucleoid: one ore several circular DNA molecules, not well demarcated, no nucleus but in separate zone
Pili (provide points of adhesion to other cells) and flagella (propel cell) made of proteins in helical arrays
Cell envelope/wall for rigidity |
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Term
|
Definition
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Term
|
Definition
| Degrades intracellular debris |
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Term
| Nucleolus (animal and plant) |
|
Definition
| Site of ribosomal RNA synthesis |
|
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Term
|
Definition
Oxidize fuel to produce ATP
Thought to be from endosymbiosis
Found in plants and animals |
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Term
|
Definition
Chloroplast: harvest sunlight, produce ATP and carbs
-CO2 fixed from air
-Thought to be from cyanobacterium (endosymbiosis)
Starch Granule: temporary storage of carbs from photosynthesis
Plasmodesma: path between two cells
Glyoxysome: contain enzymes of glyoxylate cycle |
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Term
|
Definition
| Site of lipid synthesis and drug metabolism |
|
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Term
|
Definition
| Site of much protein synthesis |
|
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Term
|
Definition
Microtubules, actin filaments, and intermediate filaments
Intracellular transport paths, movement, organization, shape |
|
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Term
|
Definition
| Inefficient - fuel not completely oxidized |
|
|
Term
| Cell Component Size Scale |
|
Definition
C-C bond 1.5 A
Alanine 5 A
DNA double helix width 20A
Bacterial cell 1-3 micron (10000 A)
EUK nucleus 1-3 micron (10000 A)
Ribosome 30 nm (300A)
Hemoglobin 5.5 nm
Membrane thickness 6 nm |
|
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Term
|
Definition
1/10th of a nm
nm x 10 = A
micron x 10000 = A
micron x 1000 = nm |
|
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Term
|
Definition
70% water
1% DNA
6% RNA
15% protein
1% ions
3% polysaccharides
2% intermediates
2% lipids |
|
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Term
|
Definition
Metabolic cofactor in all cells
Carries metabolites covalently in enzyme pathways
Contains the following functional groups:
Thioester, amido, hydroxyl, phosphoanhydride, phosphoryl, imidaxole-like, amino |
|
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Term
|
Definition
LUCA 3.5 billion yrs ago
Woese domains (eukarya, archaea, bacteria) |
|
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Term
|
Definition
Light: photoprophs
Chemical: chemotrophs |
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Term
|
Definition
Obtain energy (carbons) from inorganic source (CO2)
Oxidize the following: Hydrogen, Sulfer, iron, nitrogen, CO) |
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Term
|
Definition
Obtain energy from organic compounds (carbon source)
Final electron accepter...
O2: animals, most fungi, protists, bacteria
Not O2, but organic compounds: fermentative bacteria
Not O2, but inorganic compounds: some bacteria |
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Term
|
Definition
Use organic compounds as C source
Some bacteria (green and purple nonsulfer bacteria) |
|
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Term
|
Definition
Use CO2 as carbon source
Some use H2O to reduce CO2
-Oxygenic photosynthesis (plants, algae, cyanobacteria)
Some do not
-Anoxygenic photosynthetic bacteria |
|
|
Term
| Early Organism Energy source |
|
Definition
-May have used reduced minerals like FeS
-Later photosynthesis to fix carbon from solar energy
-Generated O2 as byproduct ---> first used to oxidize Fe
Oxidation of glucose with O2 is highly favorable --> aerobic advantage |
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Term
|
Definition
Internal cohesion
104.5 degree bond angles
4 hydrogen bonds
High BP - due to "flicker"
High mP due to max H-bonds in crystal structure |
|
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Term
|
Definition
H bond is 0.177 nm
Covalent 0.0965 nm
H bonds strongest if all 3 atoms are lined up
-H shared between two electronegative atoms
-4-6 kJ/mol if both uncharged
-6-10 kj/mol if one is charged
Covalent bond 300-500 kJ/mol
H bonds are worth a certain amount of energy that must be INPUT (positive deltaH) to break them...which is thermodynamically unfavorable...offset by huge increase in entropy
Water binds noncovalently to enzymes and plays role in binding |
|
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Term
|
Definition
| A molecule that has a hydrophobic portion and a hydrophilic portion. |
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Term
|
Definition
Physical property of a solvent, reflecting how many dipoles it has
Water has high E
-Results in low interaction (F) between charged particles like Na+Cl-
F = qQ/Er2 |
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Term
|
Definition
| Electrostatic interaction between permanently charged species or an ion + dipole |
|
|
Term
|
Definition
Uncharged, polar molecules
E.g. H bonds |
|
|
Term
|
Definition
Ordering of water molecules around nonpolar substances
Can force hydrophobic groups to hydrophobic ligand binding sites on enzymes |
|
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Term
|
Definition
London dispersion - attractive force
Steric reuplsion - repulsive force, depends on size of atoms
Attraction dominates at longer distances (3-5 A) |
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|
Term
| Solubility of Hydrophobic molecules |
|
Definition
| Low solubility due to unfavorable change in entropy for surrounding water. |
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Term
|
Definition
| Forms when all hydrophobic groups are sequestered from water |
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Term
|
Definition
Physical properties that depend on the AMOUNT of solute, NOT on the nature of the solute
E.g. bp, mp, vp, osmolarity |
|
|
Term
| Noncolligative Properties |
|
Definition
Viscosity, surface tension, taste, color
Depend on chemical nature (as opposed to the number - colligative properties) |
|
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Term
|
Definition
Measure of the force required to oppose the flow of water down concentration gradient
i = extent dissocation
c = concentration
ic = osmolarity
Strong cell walls resist osmotic pressure |
|
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Term
|
Definition
DNA -> RNA -> Protein
Unidirectional
Transcription -> translation |
|
|
Term
|
Definition
|
|
Term
|
Definition
Adenosine 2',3'-cyclic monophosphate
Important in cell signaling processes
Can form from RNA being cleaved
-Instability caused by the 2' hydroxyl group on RNA
-Reason DNA favored over RNA for passing genetic material |
|
|
Term
| Syn and Anti Conformers (Nucleotides) |
|
Definition
Rotation about the glycosidic bond
Syn is unfavored for purines due to sterics |
|
|
Term
|
Definition
At pH 7, adenine n1 and cytosine N3 are deprotonated (pH must be <4 for H to be added)
At ph 7, guanine n1, thymine/uracil n3 are protanated (and stay protonated up to about pH 10 (pH must be VERY high for them to lose H)
This has implications for BASE pairing... |
|
|
Term
|
Definition
Planar ring systems
All atoms participate in resonance (delocalization of electrons) |
|
|
Term
| Examples of Modified Bases |
|
Definition
DNA methylation
RNA modification enzymes |
|
|
Term
|
Definition
Flexibility high due to many single bonds along phosphodiester linkage
-Compared to proteins
Tertiary structure due to HYDROPHOBIC BASES wanting to stack on each other in aqueous solution
Absorb UV light with 260 nm max
Similar size and shape of AT (AU) and GC base pairs -regular shape
Asymmetrical positions of C1 atoms of sugars |
|
|
Term
|
Definition
Occur in bases
-Change H- bonds
Also, keto - enol, amino - imino |
|
|
Term
| Watson-Crick Base Pairing |
|
Definition
GC - 3 H bonds
AT(AU) - 2 H bonds
Chargaff's Rules: A=T, G=C |
|
|
Term
|
Definition
36A repeat
3.4A between each base pair
10.5 base pairs per repeat
20A wide
Large major groove for protein a-helice docking
Right-handed helix
C'2 endo sugar pucker (long P-P distance) |
|
|
Term
|
Definition
Forms from dehydrated B-DNA
Little biological significance
Short and fat -> proteins can't bind major groove
26 A diameter, 11 pairs per turn
DUPLEX RNAs due to extra 2'OH
C'3 endo sugar pucker (short P - P distance) |
|
|
Term
|
Definition
Left-handed helix
12 base pairs per turn
Important in transcrpition of DNA to RNA |
|
|
Term
| Amino Acid Stereochemistry |
|
Definition
L and D forms possible
Mostly L form found - MATCH asymmetric Enzyme active sites
(some D incorporated POST TRANSLATIONALLY)
Glycine not chiral due to two H
L form - H on the right? |
|
|
Term
| Enantiomer vs. Diastereomers |
|
Definition
Enantiomer: Stereoisomers with NONSUPERIMPOSSABLE mirror images
Diastereomer: not mirror images |
|
|
Term
|
Definition
A neutral molecule containing charges
E.g. amino acids at neutral pH 7
Predominates at pH between pKA of amino and carboxyl group
-Isoelectric point |
|
|
Term
|
Definition
Branching of the Beta carbon in some amino acids
Influences secondary polypeptide structure |
|
|
Term
| Nonpolar, aliphatic R groups |
|
Definition
Glycine
Alanine
Proline
Valine
Leucine
Isoleucine
Methionine*
Generally occupy interior of water-soluble proteins |
|
|
Term
|
Definition
Phenylalanine
Tryptophan
Tyrosine
Participate in hydrophobic/VDW intractions
Tyr and Trp are slightly polar
-Absorb UV light at 270 - 280 nm |
|
|
Term
|
Definition
Serine
Threonine
Cysteine
Asparagine (amide version of aspartate)
Glutamine (amide version of glutamate)
Can H - bond |
|
|
Term
|
Definition
Slightly Polar, uncharged amino acid
Can form disulfide bonds (OXIDIZED)
-pKA to thiolate (S-) is about 8
-At higher pH than cell, disulfide bonds occur? |
|
|
Term
| Positively Charged R groups |
|
Definition
|
|
Term
|
Definition
A (+) charge amino acid
Contains a GUANIDIUM group at the end
pKA 12 - stays protonated at physiological pH (does NOT titrate in biologically significant range) |
|
|
Term
|
Definition
(+) charged amino acid
pKA = 10, remains charged at physiological pH |
|
|
Term
|
Definition
(+) charged amino acid
pKa = 6.2...important since could either be protonated or not at physiological pH
-Efficient BUFFER at neutral pH
Contains an IMIDAZOLE group
Titrates from 2+ --> -1
(PI is between the imidazole and amino pka at 7.59) |
|
|
Term
| Negatively Charged R Groups |
|
Definition
Aspartate
Glutamate
pKA = 4.5
Carboxylate versions of asparagine and glutamine |
|
|
Term
|
Definition
Mediate ligand and protein interactions
Form salt bridges?
Interact with water on surface of protein? |
|
|
Term
|
Definition
Most are synthesized post-translationally (except selenocysteine)
Addition/removal of PHOSPHATES to Ser, Thr, Tyr
ADDED OH groups have regulatory role
Some are found in organisms but not part of protein |
|
|
Term
|
Definition
Ampholytes
Ability to be both an acid and a base
AMINO ACIDS |
|
|
Term
|
Definition
pKa of Carboxylate and amino groups affect each other
-both are LOWER than they would be independently
-NH3+ because COO- WITHDRAWS electrons
-COO- because DEPARTING H+ stabilized by NH3+
This holds for NON-IONIZING amino acid R groups
Stabilized zwitterion! |
|
|
Term
|
Definition
pKa of COO- is lowered if it is near a (+) group such as NH3+
-REPULSION between departing H and NH3+ are less stable than formation of STABLE ZWITTERION
NH3+ more likely to give up proton and LOWER pKa if near (-) group that has electron-withdrawing capability |
|
|
Term
|
Definition
When amino acid charge is 0 due to zwitterion formation
pH between pK of amino and carboxyl group
pI = (pK1 + pK2)/2 for non-ionizable R groups (glycine, etc)
AA's least soluble in water at this point |
|
|
Term
| Histidine Titration Curve |
|
Definition
|
|
Term
|
Definition
Condensation rxn -> water given off
Amino group: Nucleophile
Carboxyl: Electophile
Catalyzed by ribosome
Carboxyl C bonded to N |
|
|
Term
|
Definition
Water cutting
E.g. peptide cleavage
-Energetically favorable...but HIGH activation energy |
|
|
Term
| When is a polypeptide considered a protein? |
|
Definition
At about Mr > 10*4
1 AA = 110 Mr on average (after water leaves due to bond)
Free AA = 128 |
|
|
Term
|
Definition
Small AA more abundant
Not every protein contains all 20 |
|
|
Term
|
Definition
Groups attached to proteins
E.g. lipid, sugar, cofactors |
|
|
Term
|
Definition
Relatively low (most water is unionized)
-Low electrical conductivity
Equilibrium strongly to left (H2O <-> H+ + OH-)
Dissociation depends on TEMP
Protons transfered through chains easily due to PROTON HOPPING
-Interchangeable covalent OH and H bonds |
|
|
Term
|
Definition
Describes the extent of dissociation in equilibrium
Ka = product/reactant
Can use Ka to solve for pH
pKa = -log(Ka) |
|
|
Term
|
Definition
Absorb H+ or OH-
Rely on two equilibriums occuring (acid and water)
Within 1 pH unit of pKa value - most effective |
|
|
Term
|
Definition
| Kw = 10'14 M = [H+][-OH] = (10'7)'2 |
|
|
Term
| Carbonate/Carbonic Acid Buffer System |
|
Definition
| CO2 gas/dissolved HCO3- depends on pH |
|
|
Term
| Protein Folding Thermodynamics |
|
Definition
Decrease in entropy offset by enthalpy change
-Mostly from weak/noncovalent interactions
-H bonds, Van der Waals, electrostatic (salt bridges), HYDROPHOBIC EFFECT |
|
|
Term
|
Definition
Partial double bond character between carboxyl and N, no free rotation, planar molecules joined to C and N
Common point of rotation at alpha C
Less reactive, more stable
Certain R groups constrain conformation
-Beta branched side chains are more constrained, GLY is less constrained |
|
|
Term
| Protein Secondary Structure |
|
Definition
alpha helix: hydrogen bonds with nearby residues
beta sheet: hydrogen bonds between adjacent segments (nearby or not)
Random Coil: Irregular arrangements of polypeptide chain |
|
|
Term
|
Definition
Large macroscopic dipole
+ near N terminus (negative R groups accumulate here)
- near C terminus (positive R groups accumulate here)
Local H bonds
Right handed
E.g a-keratin |
|
|
Term
|
Definition
|
|
Term
|
Definition
Proline - no H on N due to ring
Glycine - many conformations possible other than helix
Poly Glu, Poly Arg don't form helix |
|
|
Term
|
Definition
Side chains protrude above and below
Stronger H bonds in anti-parallel
Parallel sheets require crossover connections
Anti-Parallel have BETA TURNS
GLY or PRO (cis)
-4 amino acids long
-Key H bond between first and last residue
Soft, flexible |
|
|
Term
|
Definition
Found in Type 1 Beta turns
About 6% of prolines in this conformation (opposed to 0.05% for other AAs)
Cis bonds to the peptide bond |
|
|
Term
|
Definition
Used to determine SECONDARY STRUCTURE (relative amounts of alpha vs beta structure)
Ability to absorb right/left circularly polarized light |
|
|
Term
|
Definition
Left alpha CHAINS --> Right Triple helix
-Coiled coil is 3000 A long, 15 wide
-Cross-links occur between the strands --> strenght
Gly-X-Pro repeat
-Gly most crucial --> tight packing
Some Pro --> 4-hydroxyproline
Found in tendons, cartilage |
|
|
Term
|
Definition
Right handed helix --> left coiled coil
-Hydrophobic residues pack
-Example of QUATERNARY structure |
|
|
Term
|
Definition
Changes PUCKER of proline ring --> exo at Cy
-OH allows H bonds
Added by prolyl hydroxylase (requires Vit. C)
Necessary in COLLAGEN --> prevents SCURVY |
|
|
Term
|
Definition
Enzyme that addes -OH group to proline post-translationally
Addition results in exo pucker at Cy and allows H bonds --> Collagen
Requires Vitamin C |
|
|
Term
|
Definition
Contains ANTIPARALLEL B-sheets
GLY and ALA common --> pack tightly
-VDW attraction between sheets
Silk/spider webs
Stronger than steel, but very stretchy |
|
|
Term
|
Definition
A smaller portion of polypeptide with a recognizable secondary structure
About 1000 motifs
E.g. a/b barrel
Different motifs come together --> bury hydrophobic regions |
|
|
Term
|
Definition
Usually RIGHT handed
Type 1: cis proline
Type 2: glycine |
|
|
Term
|
Definition
| Calcium binding protein with 2 DOMAINS |
|
|
Term
|
Definition
| A portion of a protein that is considered an INDEPENDENT folding unit |
|
|
Term
|
Definition
A signaling protein with INTRINSIC DISORDER at both the N-terminus and C terminus
-Unfolded portions lack hydrophobic residues
-BECOME FOLDED when interacting with different proteins |
|
|
Term
|
Definition
Heat
pH
Detergent
Solute
Break H bonds, interact with HYDROPHOBICS in core
-Leads to insolubility --> PRECIPITATION
Can be reversed |
|
|
Term
|
Definition
Rapid protein folding (milliseconds or microsecond) BUT conformation sampling would require TIME
-Heierarchical, directional folding occurs --> free energy minimum
-Local motifs |
|
|
Term
|
Definition
Prevent aggregation
No active role in folding
Require ATP
E.g. Hsp40/70 (DNAJ/DNAK)
-If doesn't fully folded --> passed to GrOE |
|
|
Term
|
Definition
Contain an aldehyde at the end of the chain
All other Carbons have an OH group |
|
|
Term
|
Definition
Contain a ketone somewhere along the chain
All other Carbons have an OH group |
|
|
Term
|
Definition
Formula CH2O
Cell-cell signaling, energy storage, structure
May contain heteroatoms |
|
|
Term
|
Definition
Most are D isomers
-At stereocenter FARTHEST from carbonyl
-H on the right
Many EPIMERS of glucose |
|
|
Term
|
Definition
A sugar with the same structure but different chirality at a given C
E.g. D-mannose vs. D-glucose |
|
|
Term
|
Definition
| The ketose form of glucose |
|
|
Term
|
Definition
| Refers to loss of water via condensation reaction of peptide bond formation |
|
|
Term
| pKa of Amino Acid (General) |
|
Definition
pK1 = -COOH (around 2.3)
pK2 = NH3+ (around 9.6) |
|
|
Term
|
Definition
Tyrosine 10
Cysteine 8.2
Lysine 10.5
Histidine 6.0
Arginine 12.5
Aspartate 3.6
Glutamate 4.3 |
|
|
Term
|
Definition
Found in proline
Reduces flexibility of polypeptide chains containing it
C=N |
|
|
Term
|
Definition
| A common amino acid modification |
|
|
Term
| Acetic Acid and Methylamine (pKA) |
|
Definition
Both contain an ionizable group with unshifted pKa
-COOH 4.8
-NH3+ 10.6
Compare to amino acids that have downshifted pKa |
|
|
Term
|
Definition
|
|
Term
|
Definition
| About 2000 amino acid residues |
|
|
Term
|
Definition
| When two protein subunits are identical --> called PROTOMERS |
|
|
Term
|
Definition
A protein that contains associated chemical components
PROSTHETIC group
E.g lipoproteins, glycoproteins, metalloproteins |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Reflects the number and kinds of bonds in a system |
|
|
Term
|
Definition
|
|
Term
| How is life possible if decrease in entropy? |
|
Definition
Endergonic reactions are coupled with exergonic reactions
OVERALL EXERGONIC
-deltaG
Eg. amino acid -> protein (endergonic)
ATP -> ADP + Pi (exergonic) |
|
|
Term
|
Definition
Provide comfortable fit for substrates -> lower Ea
Exergonic process |
|
|
Term
|
Definition
| Synthetic pathways requiring ENERGY INPUT |
|
|
Term
|
Definition
| Synthetic pathways that RELEASE ENERGY |
|
|
Term
|
Definition
Genes/proteins that contain detectable SIMILARITIES
PARALOG (same species)
ORTHOLOG (different species) |
|
|
Term
|
Definition
Amylose + amylopectin
Branched |
|
|
Term
|
Definition
| Reducing agent + unfolding agent (through hydrogen bonding, etc.) |
|
|
Term
|
Definition
| A polar solute that can denature |
|
|
Term
|
Definition
| Hydrophobic molecules that bind to hydropobic interior and denature proteins |
|
|
Term
|
Definition
R'6 dependence on attractive vs. R'12 dependence
At 2.9 Angstrom |
|
|
Term
| Nucleoside vs. Nucleotide |
|
Definition
Sugar + base
Sugar + base + phosphate |
|
|
Term
|
Definition
Anti- most biologically important
-Base not directly over sugar |
|
|
Term
|
Definition
A molecule with both HYDROPHOBIC and HYDROPHILIC components
E.g. lipids |
|
|
Term
| Lipid Organization (general) |
|
Definition
Ampipathic
Micelles
Vesicles
-Sections of bilayer can fold into vesicles
-Fuse with each other or other bilayers |
|
|
Term
|
Definition
30-100 Angstrom thick
Two monolayers (one facing cytoplasm, one facing intermembrane space or organelle interior)
Each layer may differ in composition --> functional specialization |
|
|
Term
|
Definition
Different RATIOS of the following:
Cholesterol, sphingolipids, cardiolipin, phosphatidylcholine, phosphatidylethanolamine
Functions include:
Cell boundary definition and internal compartmentalization, ion/metabolite retention, sense extracellular signals, ATP synth (mitochondria), photosynth (chloroplasts)
E.g. plasma membrane --> most abundant is cholesterol |
|
|
Term
| Transport vesicle composition (asymmetrical) |
|
Definition
Layer 1: sphingolipid + cholesterol
Layer 2: phosphatidylethanolamine + phosphatidylserine |
|
|
Term
| Trans-Golgi network composition (asymmetrical) |
|
Definition
Layer 1: Phosphatidylcholine + sphingolipid + cholesterol
Layer 2: phosphatidylethanolamine + phosphatidylserine |
|
|
Term
| Golgi composition (asymmetrical) |
|
Definition
Layer 1: phosphatidylethanolamine + phosphatidylserine
Layer 2: Phosphatidylcholine |
|
|
Term
| Fluid-Mosaic Model (bilayer) |
|
Definition
Lipids form VISCOUS, 2D solvent
-Free LATERAL movement
Protein molecules as solutes
-Peripheral, integral, or amphitropic
Carbohydrates on the OUTER LAYER
Interactions between lipids and proteins and among lipids are hydrophobic, NONCOVALENT |
|
|
Term
| Peripheral Membrane Proteins |
|
Definition
WEAKLY ATTACHED to outside or inside of bilayer
-electrostatic/H bond contact with lipid head groups
Released with mild treatement |
|
|
Term
| Integral Membrane Proteins |
|
Definition
Firmly embedded in bilayer
Removable only by DETERGENTS (coat the hydrophobic domain of the protein and remove contact with lipid hydrophobic tails)
About 20-25 a-helical AA span bilayer
6 types of alpha helical integral proteins
3 types of beta barrel proteins |
|
|
Term
| Amphitropic Membrane Proteins |
|
Definition
Sometimes associated with bilayer, depending on bioogical state
-Based on POST-TRANSLATIONAL MODIFICATION |
|
|
Term
| Types of Integral Membrane Proteins |
|
Definition
6 alpha helical (25 AA spanning membrane)
-One is covalently linked to membrane
3 B-barrel (maximize intramolecular H-bonds) |
|
|
Term
Lipid-linked Membrane Proteins
GPI (glycosylphosphatidylinositol) |
|
Definition
Firmly bound lipoproteins
Inside or outside membrane
GPI (glycosylphosphatidylinositol) as an ANCHOR on the CARBOXYL terminus of protein |
|
|
Term
|
Definition
An integral membrane protein
7 alpha-helices spanning membrane |
|
|
Term
|
Definition
Reflects ease in OIL -> WATER transfer (free energy)
High values: hydrophobic regions
PREDICTIVE POWER: 20 low values in a row --> membrane alpha helix |
|
|
Term
|
Definition
-Energy storage (highly reduced)
-Insulation (low thermal conductivity - high heat capacity)
-Mechanical protection (shock absorbent)
-Water repellent (prevents evaporation and keeps organism
dry)
-Buoyancy
-Membrane structure
-Pigment
-Enzyme cofactors, signaling molecules |
|
|
Term
|
Definition
Long, conjugated hydrophobic chains
-e.g. carotenoid pigments |
|
|
Term
|
Definition
Carboxylic acid + long hydrocarbon tail
-Usually EVEN number of carbons
-If unsaturated, double bonds usually CIS
-Number from Carboxyl end
-For polyunsaturated - use Omega system
Polyunsaturated fatty acid: double bonds NOT CONJUGATED |
|
|
Term
|
Definition
| A fatty acid chain with C16 unsaturated |
|
|
Term
|
Definition
| Fatty acid with trans double bonds due to partial dehydrogenation |
|
|
Term
| Eicosapentanoic acid (EPA) |
|
Definition
Example of a fatty acid that CANNOT BE SYNTHESIZED by humans
An Omega-3 fatty acid |
|
|
Term
| Effects of fatty acid unsaturation |
|
Definition
Cis double bonds --> kinks in the chain
-Less tight packing, less favorable interactions
Lower mp |
|
|
Term
| Effects of fatty acid chain length |
|
Definition
| Longer chain --> less solubility, higher mp |
|
|
Term
|
Definition
Form in which FATTY ACIDS are usually found
-Less soluble than fatty acids (no free, charged carboxyl group)
Less dense than water
Body fat |
|
|
Term
|
Definition
Fats more reduced --> more energy
Fats have less water due to nonpolar
Short-term storage: glucose/glycogen
Long-term storage: fats |
|
|
Term
|
Definition
Esters of long chain alcohols + fatty acid
Insoluble, high mp
Function: waterproofing, protection of hair, prevent evaporation in leaves, metabolic fuel in plankton |
|
|
Term
| Lipids not containing fatty acids |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
Phospholipids
Glycerophospholipids
Sphingolipids
Glycolipids
Sphingolipids
Archaebacterial ether lipids |
|
|
Term
|
Definition
Primary constituent of CELL MEMBRANE
Glycerol
2 fatty acid chains
PO4-X
X = ALCOHOL, choline, ethanolamine, serine, glycerol, etc
Charged PO4 at physiological pH
Usually UNSATURATED fatty acid at C2 of glyecerol-3-phosphate |
|
|
Term
|
Definition
A membrane lipid
Sphingosine - Long chain amino alcohol (No glycerol)
Only 1 fatty acid
X polar head group (often phosphocholine, glucose)
-Attached by glycosidic or phosphodiester linkage
X = often sugar if facing outside of membrane |
|
|
Term
|
Definition
| A sphingolipid often found in the myelin sheath of nerve cells |
|
|
Term
|
Definition
4 fused rings
-1 polar head group + various nonpolar side chains
-Nearly planar
MODULATE MEMBRANE thickness, fluidity, permeability
Pre-cursor for steroid hormones
Cholesterol found mostly in OUTER membrane |
|
|
Term
|
Definition
Enzyme that cleaves glycerophospholipids
-Cleaves at various locations
ETHER LIPIDS are resistant |
|
|
Term
|
Definition
May help membrane RIGIDITY, may function in SIGNALING
Lipase-resistant
Contain an ther linked alkene |
|
|
Term
|
Definition
Dramatic conformation change of a protein due to ligand binding
Example: hexokinase (enzyme) + glucose (substrate) |
|
|
Term
|
Definition
Natural, dynamic movement of protein in solution
Regardless of ligand binding |
|
|
Term
| Protein Dissociation Constants |
|
Definition
Measure of ligand binding affinity
-Ligand concentration needed for HALF SATURATION
Low Kd = good binding of protein - ligand
E.g. avidin-biotin Kd = 10'-15 |
|
|
Term
|
Definition
Heme group that binds to myoglobin and Hb
Binds a Fe2+ in center
-2 open coordination sites
-1 for Histadine, 1 for O2
CO has higher affinity for heme group than O2 |
|
|
Term
|
Definition
Low solubility in blood
-Must be carried by proteins
NO PROTEIN side chain suitable for binding O2
-Need heme group
Must be picked up in lungs, released in tissues |
|
|
Term
|
Definition
All a-helical
Single polypeptide
Heme has lower affinity for CO when in myoglobin
-Flexible HisE7 stabilized O2 (axis at angle to Fe)
HYPERBOLIC curve
Good for STORAGE
-Cant' release enough O2 in tissues unless very low concentrations
-If O2 too low, Hb can't pick up in lungs |
|
|
Term
|
Definition
a2B2 tetramer
-a and B structurally similar
O2 binds in a heme in each
T-state: less affinity for O2
-Predominates deoxyhemoglobin
-Binding triggers change to R-state
R-state: more affinity for O2
ALLOSTERIC
Successive binding of O2 improves affinity of other subunits |
|
|
Term
| Transition from T-state to R-State (hemoglobin) |
|
Definition
-Triggered by O2 binding
-Involves breakage of ion pairs between a/B subunits
-Cross-subunit salt bridges broken
Changes PROPAGATE to O2 binding site
-R state heme group is more planar |
|
|
Term
| Sigmoidal binding of Hemoglobin |
|
Definition
Cooperative
Allows rapid pick up of O2 in lungs and rapid release in tissues
Allosteric, Homotropic interaction - ligand and modulator are the same |
|
|
Term
| Example of Lock and Key Enzyme |
|
Definition
dihydrofolate reductase
Two substrates bind tightly to surface |
|
|
Term
| Classification of Enzymes |
|
Definition
Oxidoreductases (electron transfer)
Trasnferases (group transfer)
Hydrolases (hydrolysis rxn)
Isomerases, Lyases, ligases |
|
|
Term
|
Definition
| Step in enzyme reaction with the highest energy barrier |
|
|
Term
| Relationship between Keq and Standard G |
|
Definition
K-eq = 1, deltaG = 0
Increase of 5.7 kJ/mol for every 10-fold decrease of Keq |
|
|
Term
| How could an enzyme SLOW a reaction? |
|
Definition
If it is too complementary to SUBSTRATE
-Thermodynamic pit
-instead of transition state |
|
|
Term
|
Definition
Often needed to accept protons after two reactants combine
-Keeps the UNSTABLE PRODUCT from falling back to reactants |
|
|
Term
|
Definition
At low [E], initial velocity (rate of product formation) is steady
Increased [S] --> increased initial velocity
***Linear velocity increase at low [S]***
***ES = constant*** |
|
|
Term
| Multiple Substrate Enzymes |
|
Definition
Involving a TERNARY COMPLEX
Random Order: S1 and S2 can bind in ANY ORDER
Ordered: S2 can't bind until after S1
Form TWO PRODUCTS |
|
|
Term
|
Definition
Enzyme reaction with 2 substrates but no ternary complex
Enzyme forms product 1 with substrate 1 and THEN after S1 leaves, binds S2 to form product 2 |
|
|
Term
|
Definition
| Example: chymotripsin Serine nucleophile forms stable covalent adduct --> no more substrate binding |
|
|
Term
|
Definition
Competitive Inhibition
-increases Km but Vmax unaffected
-High [S] can compete back
Uncompetitive Inhibition
-Inhibitor binds a different location to S
-Binds to ES
-Decreases Km and Vmax
-Only for enzymes with 2 substrates |
|
|
Term
|
Definition
1 way to ENHANCE RATE of enzyme
Charged/Polar amino acids acting as acids/bases
His, Arg, Lys, Glu, Cys, Ser, Asp
Help stabilize transition states?
Different enzymes work best at different pH range depending on interactions |
|
|
Term
|
Definition
Rate enhancement
Forms between enzyme and substrate
Nucleophile must be on enzyme
-E.g. Serine on chymotrypsin (or amine, carboxylate, thiolate) |
|
|
Term
|
Definition
Acid/base catalysis
Covalent catalysis
Additional binding interactions (e.g. improved efficiency for distal interactions of chymotrypsin |
|
|
Term
| Nucleophiles/Electrophiles |
|
Definition
Nucleophiles: Serine, histidine, thiol, carbanion, lone pair
Electrophile, C=O, P, proton
Example:
Aldol condensation, Claisen ester condensation |
|
|
Term
| Glucose-6-phosphate ---> fructuse-6-phosphate |
|
Definition
No net change in oxidation state
C1 reduced, C2 oxidized |
|
|
Term
|
Definition
Enzyme that cleaves AA's
STEP 1
AA comes into position, Phe goes into hydrophobic pocket
O: of Ser-195 is nucleophile
Stabilized by His-57 base (takes Ser H)
Asp - His H bond increases His affinity for protons (better base)
Tetrahedral acyl enzyme (TRANSITION STATE) is formed (short-lived negative charge on O --> stabilized by H bonding in Oxy hole)
-Stabilized by Gly-193 and Ser-195
Unstable O- collapes back to double bond
Electrons go back onto N and the AA is cleaved
Amino group is protanted by His-57
STABLE COVALENT acyl enzyme INTERMEDIATE (can be isolated)
STEP 2
H2O enters
His acts again as base and DEPROTES H2O
-OH attacks carbonyl
-2nd tetrahedral transition state is formed (O- in hole)
Electrons collapse again as His donates H to O attached to Ser (REGENERATES ENZYME)
Phe at C-terminus of product 2 |
|
|
Term
|
Definition
| Enzymes that use Ser as nucleophile similar to CHYMOTRYPSIN |
|
|
Term
| Catalytic Triad of Chymotrypsin |
|
Definition
|
|
Term
| Determination of RATE LIMITING step for Chymotrypsin |
|
Definition
Early burst ---> proves fast step at beginning
Use p-Nitrophenol as a stand in substrate since it covalently attaches the same was a peptide |
|
|
Term
| pH Profile of Chymotrypsin |
|
Definition
pKa: at low pH, enzyme killed because His is unlikely to give up protons (needed for slow step - enzyme reformation)
Efficiency: kcat/km best between ph = 6-9
-kcat maxes at high pH
Km: Km increases at higher pH due to Ile (after zymogen cleavage)
-High pH = deprotonation of N-terminus
-NH3+ of Ile needs to be charged in order to bury into structure |
|
|
Term
|
Definition
Chymotrypsin activated in gut by TRYPSIN
-Cleaves at Ile-16
-Charged NH3+ buries in structure and activates enzyme
-Salt bridge with Asp-194
Irreversible cleavage |
|
|
Term
|
Definition
H2O as Nucleophile -aided by (Asp base catalysis)
Attacks carbonyl of amino acid
Tetrahedral transition state
Collapse followed by Lg protonation (Asp acid catalysis)
HIV drugs mimic the O- of the tetrahedral transition state
(OH mimics)
-Benzyl group positions drug (mimics Phe of amino acid substrate) |
|
|
Term
| Enolase Reaction Mechanism |
|
Definition
An enzyme stabilized by 2 Mg++
-makes proton on substrate more acidic
Lys: base
Phosphoenolpyruvate |
|
|
Term
| Heterotrophic Allosteric Inhibition |
|
Definition
Different modulator and substrate
Reversible noncovalent bonds formed at a regulatory location
-E.g. Ile down the chain binds at regulatory site |
|
|
Term
|
Definition
Usually a separate CATALYTIC and REGULATORY subunit
Positive Effector: binds and changes enzyme from T --> R state
Homotropic effector: same as substrate
Heterotropic effector: different modulator and substrate
Ex. Aspartate transcarbamoylase binding ATP or CTP
ATP positive modulator, CTP negative modulator
-K.0.5 changed, but Vmax is not |
|
|
Term
| Covalent Enzyme modification |
|
Definition
For regulatory control
Phosphorylation
Adenylation
Acetylation
Myristoylation
Ubiquitination
ADP-ribosylation
Methylation
Zymogen activation of serine proteases (chymotrypsin |
|
|
Term
|
Definition
Two serine sidechains become PHOSPHORYLATED
-More active version of the enzyme
Example of covalent enzyme modification |
|
|
Term
|
Definition
An enzyme that is part of the carbohydrate metabolism
Multiple phosphorylation sites to finely modulate |
|
|
Term
|
Definition
| Couple an unfavorable rxn with a favorable one |
|
|
Term
| Why ATP hydrolysis is favorable? |
|
Definition
Relieve charge repulsion
Pi is stabilized resonance hybrid
ADP and Pi better solvated overall than ATP
ATP is thermodynamically UNSTABLE but kinetically stable |
|
|
Term
|
Definition
Hydrolized to pyruvate + Pi
More favorable than ATP hydrolysis (-43.0 kj/mol)
A GLYCOLYTIC RXN |
|
|
Term
| 1,3 - bisphosphoglycerate |
|
Definition
A GLYCOLYTIC RXN that is highly favorable (-49.3 kJ/mol)
Releases Pi2- and 3-phosphoglycerate |
|
|
Term
| Order of energy for GLYCOLYTIC RXNS |
|
Definition
Phosphoenol pyruvate -> 1,3 bisphosphoglycerate -> phosphocreatine --> ATP
Low energy: G6P, glycerol-P |
|
|
Term
| Acetyl-CoA thioester hydrolysis |
|
Definition
Releases as much energy as ATP hydrolysis
The Oxygen ester is more resonance stabilized --> smaller change in free energy |
|
|
Term
|
Definition
2 steps with "activated" intermediate with a Pi added from ATP, then the Pi leaves as another group is added
E.g. Glutamate --> Glutamine
Usual way of getting free energy from ATP, except in molecular motion rxns |
|
|
Term
|
Definition
When the gamma P group is removed from ATP
Produces ADP + RO:PO3 |
|
|
Term
|
Definition
When the B P group is attacked on ATP
Produces AMP + RO:P2O6 |
|
|
Term
|
Definition
Attack at the a P of ATP
Produces PPi and RO:PO3
VERY FAVORABLE (fatty acid oxidation)
ATP -> AMP + pyrophosphate |
|
|
Term
|
Definition
Enzyme that cleaves pyrophosphate (PPi) and drives DNA/RNA synthesis
Occurs after the OH of RNA attacks ATP and removes the PPi |
|
|
Term
|
Definition
|
|
Term
| Compartmentalization in Biosynthesis |
|
Definition
| Fuel oxidation and reduction in separate compartments |
|
|
Term
|
Definition
| Variable reducing agent (can transfer 1 or 2 e-)? |
|
|
Term
|
Definition
Glycerol + 3 fatty acid side chains
Adiposite = fat cell |
|
|
Term
|
Definition
| Allow buildup of LDL (cholesterol) |
|
|
Term
|
Definition
Process of moving things in bilayer
1 micron/second
Flippase, floppase, scramblase are enzymes |
|
|
Term
|
Definition
| Found mostly in the inner membrane of mitochondria |
|
|
Term
| Membrane proteins are orgaized by... |
|
Definition
How easily they can be removed from the membrane
Peripheral: weak
Integral: firm
Amphitropic: sometimes associated (anchored with lipids, etc. --membrane protein wannabe |
|
|
Term
| Amphitropic membrane Protein |
|
Definition
Wannabe membrane protein
Anchored by lipids, sugars, etc.
Only sometimes associated |
|
|
Term
| Why no beta sheets in membrane proteins? |
|
Definition
Beta sheets have exposed residues at end of sheet (polar hydrogen bonding groups pointing into the lipid NH3+, COO-)
Instead find beta barrel |
|
|
Term
|
Definition
NO catalytic activity
Lock and key: no change occurs after binding
Induced fit: conformational change when ligand binds |
|
|
Term
|
Definition
The amount of myoglobin bound
Usually on Y axis |
|
|
Term
|
Definition
The substrate in the active site
Non: the other stuff down the chain that interacts with enzyme |
|
|
Term
|
Definition
| Binding of a ligand affects binding at another site |
|
|
Term
|
Definition
|
|
Term
|
Definition
Example of induced fit
Binds glucose
-O of glucose attacks electrophilic P
Induced fit SEQUESTERS ATP away from water (high concentrations of H20 may compete) |
|
|
Term
|
Definition
pH = 7
1 M concentration
mM of Mg
1 atm
298 K |
|
|
Term
| Mechanism for Stabilizing Transition states |
|
Definition
Induced fit
Desolvation
Chemical catalysis (proximity, acid/base, metal ion) |
|
|
Term
|
Definition
kcat/Km
Efficiency of an enzyme |
|
|
Term
| 8 Ways to regulate Enzymes |
|
Definition
1. Zymogen activation (irreversible)
2. Product Inhibition
-Product rebinds the active site if too much of it
3. Substrate/Cofactor concentration
4. Modulator Proteins
-Binding of one protein (as substrate) to regulatory subunit of another protein
5. Genetic Control (long time)
E.g. glycogen phosphorylase ( in response to glycogen phosphorylase)
6. Isozymes
Closely related enzymes doing the "same" rxn
7. Covalent modification
8. Allostery: conformation change occurs from molecules acting at a distance |
|
|
Term
|
Definition
Tetramer with 2 a and 2 B chains.
Interconverts lactate and pyruvate
NAD to NADH, H+
10 different ISOZYMES
-THe K is effected by the amount of a/B
-More a favores pyruvate |
|
|
Term
| Covalent Enzyme modification |
|
Definition
Very fast
Often reversible (different enzymes for adding and removing)
E.g. phosphorylation |
|
|
Term
|
Definition
A type of covalent modification of enzymes
Coenzyme A |
|
|
Term
|
Definition
A type of covalent modification of enzymes
Coenzyme A
Tagging things for membrane association |
|
|
Term
|
Definition
| Adding a suger to a protein |
|
|
Term
|
Definition
|
|
Term
| Why is ATP kinetically stable? |
|
Definition
| OH must get in past negative charge to attack P and cleave |
|
|
Term
|
Definition
Substrate-level phosphorylation
-Thermodynamically downhill driving ATP formation
Oxidative Phosphorylation (ATP synthase) |
|
|
Term
|
Definition
1. Pyruvate via glycolyisis
2. Glycogen starch (storage)
3. Cellulose (structural)
4. Ribose-5-phosphate (nucleic acid synthesis) |
|
|
Term
| 5 general types of reactions |
|
Definition
1. C-C, C-H bond breaking/making
2. Internal rearrangement, isomerization, elimination ,etc.
3. Group transfer
4. Redox (with other molecules)
5. Free radical reactions
1-4 occur in glycolysis pathway |
|
|
Term
|
Definition
Group transfer rxn, occurs in step 1 and 3 of glycolysis
Add 1 a phosphoryl group to glucose using HEXOKINASE
Phosphoryl comes from ATP
Generally IRREVERSIBLE and THERMODYNAMICALLY FAVORABLE |
|
|
Term
|
Definition
Rearrangement rxns
E.g. glucose-6-phosphate to fructose-6-phosphate in step 2 of glycolysis |
|
|
Term
|
Definition
Enzyme that cleaves Fructose 1,6 bisphosphate to G3P + dihydroxyacetone phosphate
CLEAVAGE ENZYME of step 4 of glycolysis |
|
|
Term
|
Definition
Phosphorylation enzymes
E.g. hexokinase and phosphofructokinase
Generally use Mg2+ as a cofactor |
|
|
Term
|
Definition
Enzymes that rearrange molecules
E.g. phosphohexose isomerase (step 2 glycolysis)
E.g. Triose phosphate isomerase (TIM, step 5 glycolysis) |
|
|
Term
| Triose phosphate Isomerase |
|
Definition
Converts all dihydroxyacetone phosphate to glyceraldehyde-3-phosphate in step 5 of glycolysis
delta G prime = 7.5 |
|
|
Term
| Glyceraldehyde 3-phosphate dehydrogenase |
|
Definition
Enzyme responsible for the oxidation/phosphorylation of G3P in step 6 of glycolysis
Reduces NAD+ in the process |
|
|
Term
|
Definition
Enzyme that phosphorylates ADP in step 7 of glycolysis to FORM ATP
1,3 bisphosphogylcerate -> 3-phosphoglycerate |
|
|
Term
|
Definition
| Rearranges the 3-phosphoglycerate molecule to 2-phosphoglycerate in step 8 of glycolysis |
|
|
Term
|
Definition
Enzyme that removes water from 2-phosphoglycerate to form phosphoenolpyruvate (glycolysis step 9)
Dehydration, Condensation, or Elimination (Rearrangement) |
|
|
Term
|
Definition
Enzyme that produces 2 ATP by phosphorylating ADP from phosphophoenolpyruvate (glycolysis 10)
Ultimately forms PYRUVATE
Mg2+, K+ cofactors |
|
|
Term
|
Definition
1. Anabolic reactions to BUILD MOLECULES
2. Ethanol + 2CO2 (yeast fermentation)
3. 2 Lactate (fermentation in vigorously contracting muscle)
4. 2 Acetyl-CoA -> 4CO2 + 4H2O (citric acid cycle)
2 and 3 are ANAEROBIC
4 is AEROBIC |
|
|
Term
|
Definition
Enzyme that phosphorylates many hexoses (e.g. glucose in glycolysis)
Thermodynamically favorable rxn
Induced fit blocks out H2O
IRREVERSIBLE |
|
|
Term
|
Definition
Enzyme that rearranges G6P to F6P (glycolysis step 2)
Thermodynamically unfavorable (just barely)
Works on the LINEAR FORM of the sugar, although cyclic form is predominant in solution |
|
|
Term
| Product of glycolysis that is committed to the pathway once formed |
|
Definition
| Fructose 1,6-bisphosphate |
|
|
Term
| Importance of step 3 of glycolysis |
|
Definition
Irreversible phosphorylation to form fructose 1,6 - bisphosphate
Important step for REGULATION |
|
|
Term
| Pyruvate Dehydrogenase (general) |
|
Definition
Enzyme complex that catalyzes: PYRUVATE --> Acetyl-CoA
5 cofactors
Massive enzyme with 3 SUBUNITS (many of each per particle)
Found in the mitochondrial matrix
Forms 2 NADH (one from each pyruvate)
2 CO2 out
IRREVERSIBLE (delta G prime = -33)
VERY LARGE (Mr = 7.8 x 10'6
Similar to a-ketoglutarate dehydrogenase complex of TCA |
|
|
Term
|
Definition
1. TPP
2. Lipoate (attached to Lysine)
3. CoA-SH
4. FAD
5. NAD+
TPP, Lipoate and FAD stay on enzyme |
|
|
Term
|
Definition
| Channel that allows pyruvate to penetrate the mitochondrial inner membrane |
|
|
Term
|
Definition
1. Decarboxylation (CO2 out) and attachment to TPP
2. Redox to make SH on lipoic acid
3. CoA from CoA-SH displaces lipoic acid --> ACETYL-COA
4. Two -SH on lipoyl pass e- to FAD --> FADH2 and oxidation of lipoic acid back to S-S
5. Pass electrons to NAD+ --> NADH + H+ |
|
|
Term
|
Definition
Group transfer reactions
Require ATP
Phosphorylate the sugar
Energetically very favorable --> reversible
Kinases |
|
|
Term
|
Definition
Isomerization reaction from pyranose to furanose
IMPORTANT BECAUSE...need carbonyl at C2 for C-C splitting in step 4
deltaG prime = 1.7 |
|
|
Term
|
Definition
Cleavage step --> DHAP, G3P by ALDOLASE
deltaG prime = 23.8, deltaG cell = very small due to concentrations....driven forward
Reversed in GLUCONEOGENESIS
G3P derived from C4,5,6 |
|
|
Term
| Step 2 of Glycolysis Mechanism |
|
Definition
| Catalytic base/acid: Glu residue |
|
|
Term
| Glycolysis Step 4 Mechanism |
|
Definition
LEFT: Lysine, base below
RIGHT: Acid, base below
1. Lys attacks carbonyl at C2 while acid on other side donates proton (TETRAHEDRAL INTERMEDIATE)
2. B: below Lys takes an H+ while H+ from solution is attacked by -OH (leaves as H2O) --> double bond N=Carbonyl (SCHIFF BASE)
3. Base below acid on right attacks -OH at C4, carbonyl formed, C-C bond breaks, electrons onto N+ ---> G3P leaves (REVERSE ALDOL CONDENSATION)
4. Electrons off of N --> reform protonated SCHIFF BASE
5. H2O hydrolizes Schiff base --> DHAP formed (reverse of steps 1 & 2) |
|
|
Term
|
Definition
G3P + Pi + NAD+ --> NADH + 1,3-bisphosphoglycerate
The only redox step + a group transfer
G3P dehydrogenase |
|
|
Term
|
Definition
1,3-bisphophoglycerate + ADP --> ATP + 3-phosphoglycerate
Phosphoglycerate KINASE
Substrate-level phosphorylation (1st ATP made) |
|
|
Term
|
Definition
3-Phosphogylcerate --> 2-phosphoglycerate
Phosphoglycerate MUTASE
delta G prime = 4.4 |
|
|
Term
|
Definition
Redox + group transfer
Form ACYL PHOSPHATE (conserves free energy of oxidation) while reducing NAD+
deltaG prime = 6.3
GLYCERALDEHYDE PHOSPHATE DEHYDROGENASE |
|
|
Term
| Glycolysis Step 6 Mechanism |
|
Definition
1. Cys-S- pKA shift down to 5.5 due to nearby NAD+...Cys acts as nucleophile to attack aldehyde of G3P
2. Tetrahedral covalent enzyme-substrate complex (thiolate)
3. Electrons collapse off O- back to carbonyl, NAD+ takes up H+
4.NADH leaves active site, NEW NAD+ enters, Pi enters
5. Pi attacks carbonyl, Cys-S detached....1,3-bisphosphoglycerate
His next to Cys helps to LOWER PKA |
|
|
Term
| Glycolysis Step 8 Mechanism |
|
Definition
2 His residues in active site of phosphoglycerate MUTASE
-One Shuttles
-One acts as acid/base catalyst
1. One His is pre-phosphorylated, C2 attacks it, the other His takes the H+ from C2 (base)
3. Original His N: attacks PO3 on C3, protonated His donates H+ back to C3 |
|
|
Term
|
Definition
Enolase
Dehydration to form phosphoenolpyruvate
delta G Prime = 7.5 |
|
|
Term
| Glycolysis Step 9 Mechanism |
|
Definition
1. H is made more acidic by a 2Mg2+ stabilizing the COO-, Lys (pKa shifted down to neutral form) takes proton...C=C formed
2. Glu (pKa UP) next to Lys donates H+, leaves as H2O |
|
|
Term
| Irreversible steps of Glycolysis |
|
Definition
1, 3 and 10
Hexokinase, PFK-1, pyruvate kinase
Bypassed in GLUCONEOGENESIS (the other 7 are shared)
Step 7, although it involves ATP and uses a Kinase, IS REVERSIBLE |
|
|
Term
|
Definition
An example of ANAEROBIC METABOLISM.
Enzyme that reduces pyruvate --> Lactate
Regenerates NAD+
-Aeoribic organisms regenerate it in ETC |
|
|
Term
| What is the fuel input to the TCA and where does it come from? |
|
Definition
Acetyl-CoA
From amino acid, fat, and sugar pathways (all converge on this metabolite) |
|
|
Term
| Location of Glycolysis, PDC, TCA, Ox phos |
|
Definition
Glycolysis: Cytoplasm
PDC, TCA: Mitochondrial matrix
Ox Phos: Inner Mitochondrial membrane |
|
|
Term
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Definition
Fuel input of PDC (comes from sugar, fat, or AA breakdown)
High energy thioester bond formed from Coenzyme-A + pyruvate
2 carbons
Formation reduces NAD+ to NADH |
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Term
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Definition
Mr = 7.8 x 10'6 Da
Dia = 50 nm |
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Term
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Definition
WHEN CATALYTIC SITES on a multi-enzyme complex are near enough to pass substrate
E.g. PDC - LIPOATE COFACTOR is the key, occurs on SURFACE
Minimizes side reactions
Subject to regulation (by other enzymes attached to PDC) |
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Term
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Definition
Key component for channeling in PDC
Covalently attached to Lys of E2
S-S bond in oxidized form
Two S-H bonds in reduced form
Acetylated form contains 1 S-H and 1 thioester |
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Term
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Definition
Cofactor that works in E1 of PDC
Oxidizes the CO2 that leaves --> forms hydroxyethyl TPP (covalently bonded to the rest of pyruvate)
Stays on enzyme (non-diffusible) |
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Term
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Definition
1. DECARBOXYLATION of pyruvate by TPP --> hydroxyethyl TPP ( SLOW STEP)
2. Reduction of both S's on liopic acid, then one linked to ACETATE
3. TRANSESTERIFICATION (CoA-SH replaces lipoyl in active site of E2 and lipoyl reduced again) --> Acetyl-CoA released, reduced lipoyl to E3
4. Lipoyl reduces FAD --> FADH2
5. FADH2 -> gives e- to NAD --> NADH + FAD reoxidized |
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Term
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Definition
The product of TPP oxidizing the carboxylic acid end of pyruvate (CO2 leaves)
SLOW STEP of PDC |
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Term
TCA TRIVIA:
1. Which steps release CO2?
2. Which products are symmetric?
3. How many substrate-level phosphorylations?
4. Which steps are irreversible |
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Definition
1. 3 & 4 release CO2
2. Succinate and fumarate are symmetric
3. 1 Sub-level phosphorylation
4. 1, 3, and 4 are irreversible |
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Term
| Anaplerotic chemical reactions |
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Definition
| Reactions that reform metabolic precursors |
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Term
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Definition
1. Citrate formation
2. Isomerization (2 parts: dehydration, hydration)
3. Oxidative decarboxylation (give NADH + CO2 leaves)
4. Same as 3 but using CoA-SH
5. Substrate-level phosphorylation
6. Dehydrogenation --> FADH2
7. Hydration
8. Dehydrogenation to Oxaloacetate, NADH formed |
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Term
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Definition
Citrate Synthase enzyme
Oxaloacetate + Acetyl-Coa ===> CITRATE
-Ox-Ac must bind first for INDUCED FIT (ordered)
dG' = -32 (driven by hydrolysis of thioster) --> essentially IRREVERSIBLE
CLAISEN CONDENSATION (H2O in, CoA-SH out) |
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Term
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Definition
Aconitase
Forms CIS-ACONITATE
H2O elimination (facilitated by Fe-S center held in place by Cysteines)
-Proton extraction from C2
RARE: Fe cluster but no redox!
-Lowers H2O pKa --> promotes ionization |
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Term
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Definition
Aconitase
H2O attacks to form ISOCITRATE (could form citrate) |
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Term
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Definition
Molecules with NO CHIRAL center that are able to react asymmetrically in active site of enzyme
E.g. Citrate - 3 attachment points |
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Term
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Definition
Isocitrate dehydrogenase
Isocitrate --> a-KETOGLUTARATE + CO2
NAD+ reduced
Intermediate stabilized by MANGANESE
dG' = -21 |
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Term
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Definition
a-ketoglutarate dehydrogenase
-Similar mech. to PDC (same cofactors, different active site sizes for new substrates)
Form SUCCINYL-CoA and CO2 LEAVES from a-keto + CoA-SH
Reduce NAD+ -> NADH
dG' = -33 |
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Term
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Definition
Succinyl-CoA synthetase
Substrate-level phosphorylation
-GDP + Pi in
-Form GTP, CoA-SH out
Ultimately form SUCCINATE
dG' = -2.9 |
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Term
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Definition
1. Pi attacks Succinyl-CoA forming Succinyl-phosphate intermediate, CoA-SH released
2. His in active site attacks the phosphoryl, e- back onto O
3. GDP + H+ enter and Pi attacks --> GTP (dG = 0)
High energy bonds conserved in ATP, Phospho-His covalent intermediate |
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Term
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Definition
Succinate dehydrogenase (bound tightly to inter. mit. membrane)
Oxidation of succinate --> FUMARATE
-E- to FAD --> Fe-S --> Q --> O2
Dehydrogenation
dG' = 0 |
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Term
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Definition
Fumarase
-Specific for trans isomer of fumarate
-CARBANION transition state
Fumarate hydration to MALATE
Hydration
Reversible
-Reverse is specific for L-malate
dG' = -3.8 |
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Term
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Definition
Malate Dehydrogenase
Highly unfavorable, dG = 30
-Driven by favorable formation of citrate
-Low concentrations of oxaloacetate in cells
Formation of OXALOACETATE
REDUCTION OF NAD |
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Term
| Overall ATP yield and Amount of Energy from Glycolysis, PDC, TCA |
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Definition
30-32 AT per glucose
30.5 kJ/mol per ATP
About 976 kJ/mol |
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Term
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Definition
ATP synthase faces the outside of membrane in thylakoids, with the a + charge on the inside of the matrix and - on the outside
Opposite of Oxidative Phosphorylation
-Proton gradient & redox
Electrons flow to NADP+ (instead of O2)
H2O is e- donor |
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Term
| Mitochondrial Matrix Contains: |
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Definition
PDC
TCA
Fatty acid, amino acid oxidation enzymes |
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Term
| Inner Mitochondrial Matrix Contains: |
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Definition
ETC
ATP Synthase
ADP-ATP translocase
Other membrane transporter
Succinate dehydrogenase? |
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Term
| What is ATP synthase ultimately driven by? |
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Definition
A transmembrane electrochemical potential
-based on both CONCENTRATION and ELECTRICAL POTENTIAL
Chemical gradient (pH, alkaline inside) - concentration
Electrical - negative inside |
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Term
| Secondary Active Transport |
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Definition
An ion moves against its gradient with the aid of a different molecule moving down its gradient
E.g. Pi in and H+ out of mit. matrix |
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Term
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Definition
Lipid-soluble --> freely diffusible in membrane
3 oxidation states
Functions as 1 or 2 e- carrier (as well as proton carrier) |
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Term
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Definition
| Fully reduced form of Q, holds 2 e- and 2 H+ |
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Term
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Definition
Contain covalently or non-covalently attached HEME group
-COVALENT in CYT C
Different reduction potentials
Integral or membrane associated proteins |
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Term
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Definition
Iron surrounded by Cys residues
One e- transfers, receive e- from Q
8+ in ETC (Complex I & II) |
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Term
| Order of E- Transfer in ETC |
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Definition
NADH -> FADH2 -> Q -> Fe-S -> Cyt C -> O2
Downhill flow of electrons
H20 has the highest reduction potential, so it wants the electrons most |
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Term
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Definition
| The detergent used to break up mitochondria |
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Term
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Definition
Carries electrons between Complex 3 and 4
Diffusible in intermembrane space |
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Term
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Definition
Accept e- from NADH
Regenerates NAD+
Contains Fe-S complex
Transfer of 4 H+ to intermembrane space (VECTORIAL TRANSFER)
-NADH + 5e- ---> QH2 + NAD+ + 4H+
-Coupled because proton transfer is disfavored |
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Term
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Definition
Receives e- from succinate
Same as step 6 in TCA
3 Fe-S centers |
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Term
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Definition
Complex 1 (NADH)
Complex 2 (FADH)
Fatty acyl-CoA --> FAD (OUTSIDE)
Glycerol 3-phosphate --> FAD (OUTSIDE) |
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Term
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Definition
Dimeric complex
Interacts with Cyt. C in intermembrane space
Donates e- via Two Q binding sites --> Q cycle
-Each Q donates 1 e- to Fe-S -> Cyt C.
-The other e- goes to a Q --> Q-
Do this twice and take in 2 H+ from matrix --> REGENERATE QH2
VECTORIAL TRANSPORT: 4H+ released to intermembrane space |
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Term
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Definition
Electron flow: From Cyt C --> Fe-Cu center -> Heme -> O2
Binuclear center?
4e-, 4H+ (1 at a time) needed to reduce O2 to 2H2O
-Another 4H+ pumped into intermembrane space
-E- come from 4Cyt-C-Fe2+ ---> oxidized to Fe3+ |
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Term
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Definition
| Blocks reduction of O2 in complex IV |
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Term
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Definition
| An antibiotic that blocks ATP synthase |
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Term
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Definition
Pokes holes in inner mitochondrial membrane --> breaks down proton gradient
O2 consumption not interrupted |
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Term
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Definition
F1 peripheral: ATP synthesis
Fo integral : proton motive force
ADP oxygen attacks Pi, H2O leaves
-Pentacovalent transition state, needs Mg2+
-Active site contains Glu, Lys, Arg
Binds ATP very tightly 10'7 tighter than ADP
-Proton motive force dislodges ATP |
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Term
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Definition
The active sites
One bound to ATP, one to ADP, one is empty
Gamma rotates and interacts |
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Term
| Adenine Nucleotide Translocase |
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Definition
Protein that transports ADP in and ATP out
-Favored by H+ gradient (ATP is 4- so it is favored to go into inter. membrane)
Antiporter |
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Term
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Definition
Protein that brings Pi into matrix (H2PO4)
H+ down gradient (dissipates the H+ gradient a little) into matrix
Symporter |
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Term
| Succinate vs. NADH for H+ in ETC |
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Definition
10 H+ per NADH
6 H+ per Succinate
P/O ratio |
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Term
| Getting 2.5 ATP from NADH of Glycolysis |
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Definition
Malate Aspartate shuttle
NADH moves into matrix
Liver, kidney and heart mitochondria |
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Term
| Glycerol-3-Phosphate Shuttle |
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Definition
Skeletal muscle and brain
NADH from glycolysis --> Glycerol-3-phosphate (from DHAP being reduced) --> FAD --> QH2 |
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Term
| How many ATP from Acetyl-CoA? |
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Definition
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