Test 3 Flashcards
Complex I can leak what ____ toward the matrix?
O2
Complex III generates O2 where?
toward both matrix and inter-membrane space
When the cell is stressed it has what moved into the mitochondria.
apoptotic pathways, P66^she
P66 ^she is part of apoptosis generating _____ molecules.
ROS
How does P66^she accomplish apoptosis.
it accomplishes this by subtracting electrons from cytochrome c to produce O2
____ is highly regulated event in a cell. preventing apotosis.
ROS production
In a cell that has not signaled apoptosis O2 is dismutated to ____
H2O2
what dismutated H2O2
Cu, Zn, SOD (Super-oxide dismutatse)
What happens in the mitochondria after O2 is reduced to H2O2.
it is reduced to H2O by glutathione peroxidase (GPX) using GSH (glutathione), and the resultant oxidized glutathione (GSSG) is reduced back to GSH by glutathione reductase
A typical mammalian liver mitochondria has roughly ______ copies of the ATP synthase
15,000
Homologous versions of the ATP synthase are found?
plasma membrane of aerobic, bacteria, the thylakoid membrane of plant chloroplasts, and the inner mt membrane
Recent high-resolution EM work suggests that the two portions of the ATP synthase are connected by___
central peripheral stalk
ATP synthesizing enzyme has what two parts
F1 head, F0 (Fnot) basal section
F1
a spherical head
F0 (Fnot)
a basal section embedded in the inner membrane
The generated proton gradient is then used to make ATP via a protein complex known by several names
Fnot/F1 complex, ATP synthase, complex V (out of date)
Endergonic process is driven by ______ in energy level of the electron as it passes through.
reduction
what two enzymes are not part of the four complexes?
cytochrome c, ubiquinone (CoQ)
enzymes that transfer pairs of electrons from substrates to molecules such as the conenzymes NAD+ and FADH are called
dehydrogenases
Pathway by which monosaccharides are broken down
glycolysis
name an example of a monosaccharide in glycolysis
glucose
where does glycolysis occur
cytosol of eukaryotic cells and in prokaryotes
what three important molecules are generated during glycolysis
2ATP, 2pyruvate, 2NADH
The cyclic pathway that occurs in the matrix of mitochondrion
tricarboxilic acid cycle(TCA), citric acid cycle, krebs cycle,
What is a sybstrate for TCA
acetyl CoA
How is acetyl CoA formed?
via B-oxidation pathway in the mitochondrial matrix and in the peroxisome
by the transition reaction as pyruvate crosses the mitochondrial membranes generates?
1 NADH and releases 1 CO2
3 important molecules formed during TCA
2 ATP, 6 NADH, 2 FADH2, (2 CO2 are formed)
The high-energy electrons associated with NADH and FADH2 are transferred (dumped) to a series of specific electron carriers that constitute the ______ located in the inner mitochondrial membrane
ETC(Electron Transport Chain)
Lowest energy electrons are ultimately passed to molecular oxygen from ____
Complex IV
These protein complexes will use energy from the elections to establish a _____
H+ gradient withing the inter membrane space
The stored H+ gradient will power the endergonic process of synthesizing ATP via secondary or indirect active transport by the _____
F0/F1 complex
The ___ ETC complexes are composed of _____ types of membrane-bound electron carrier proteins
4,5
a polypeptide bound tightly to one of two related prosthetic groups
flavoproteins
proteins that contain heme prosthetic groups
cytochromes
both groups are derived from riboflavin (vitamin B2)
Flavin Adenine Dinucleotide (FAD) or Flavin Mononucleotide (FMN)
copper attoms are all located within ___
complex IV
Copper atoms alternate between
Cu^2+, Cu+1
lipid-soluble molecule containing a long hydrophobic chain composed of 5-carbon isoprenoid units
ubiquinone
ubiquinone is able to accept ____ electrons and protons
2
Where does ubiquinone reside
lipid bi-layer and moves about freely
contain iron not in a heme group, but that is instead linked to inorganic sulfur atoms
iron sulfur
iron- sulfur donates ___ electrons
single
Glycolisis makes
net gain 2 ATP, 2 pyruvate, 2 NADH
TCA cycle, citric acid cycle, and Krebs cycle
2 ATP 6 NADH, 2CO2
What is the pathway by which monosaccharides (such as glucose) are broken down
glycolysis
Where does glycolysis occur
cytosol of eukaryotic cells and in prokaryotes
enzymes that transfer pairs of electrons from substrates to molecules such as the coenzymes NAD+ and FADH (empty wheelbarrows)
dehydrogenases
The pathways of glycolyisis and TCA are rich in _____ some termed dehydrogenases
proteins
Solution withing inner membrane of the mitochondria is termed
matrix
what is the sight of the TCA pathway
matrix
Where does the mitochondrial gene expression and genome replication occur
matrix
the infoldings of membrane in the mitochondria are termed_____
cristae
The space between membranes in the mitochondria is termed the ________
intermembrane space
mitochondria is _____ part of the endomembrane system
not
mitochondria are ______, meaning they grow and divide within the cell and generate some of the proteins that function there, and take up others from the cytoplasm
semiautonomous
Mitochondria have there own
DNA and ribosomes
mitochondria are about ____ in diameter
1-10um
Glucose moves across the apical plasma membrane against a concentration gradient by
Na+ contransport (symport)
The needed Na+ gradient is maintained by _____ by the Na+/K+ -ATPase pump in the basal and lateral membranes of the cells
active transport
Finally the glucose molecules move into the blood stream by ____ _____ through a glucose transporter (glucose permease)
facilitated diffusion
Tums and Rolaids work by neutralizing
acid (H+) in the stomach
Zantac, Pepcid, and Tagamet work instead by
blocking receptors on the surface
Over secretion of acid can lead to _______
heartburn
The epithelial lining of the stomach contains a _____ which secreetes a solution of concentrated acid (up to 0.16 NHCL) into the stomach chamber
H+/K+ -ATP
In the resting state of transport proteins are situated in the membranes of
cytosolic vesicles
When food enters the stomach a hormonal message is transmitted to the parietal cell causing the ______ vesicles to move to the ______ cell surface and begin secreting acid.
pump-containing, apical
an example binds at a cell surface receptor triggering cellular signal transduction
histamine
Driving exergonic reaction here is the use of the Na+ is present to bind simultaneously
sodium-glucose symport
Cells lining our intestine are able to take up molecules like glucose or amino acids from the lumen into the cells even when the cellular concentration is higher than the lumen concentration
sodium-glucose symport
The subsequent facilitated diffusion of Na+ back across the membrane drives the intake of glucose, and other molecules this is termed
indirect active transport or secondary active transport
what pump is found only in animals, although other species accomplish the same tasks with analogous mechanisms and proteins
sodium-potassium pump
the sodium -potassium pump has a ____ ____ for Na+ with binding sites oriented towards the cytoplasm
high affinity
The sodium-potassium pump has a high affinity for ____ with binding sites oriented towards the cell’s exterior.
K+
termed ____ ___ in nonexciteable cells (those other than neurons and muscle)
membrane potential
termed a _____ _____ in neurons and muscle cells
resting potential
Such _____ movement ofions requires being coupled to an _____ reaction such as
endergonic, exergonic
____ depends on integral membrane proteins that selectvely bind a particular solute and move it across the membrane against its concentration gradient in a process driven by energy requiring changes in the protein’s conformation.
active transport
proteins that carry out active transport are often referred to as ____
pumps
very similar to facilitated diffusion but it moves molecules against a concentration gradient and therefore, requires an energy input
active transport
Typically the K+ concentration inside a mammalian is ___
higher
typically, the Na+ concentration is ____ on the outside
higher
Ca+ concentration gradient is very large _____ cell
outside of the cell
Today there are a considerable number of inherited ion channel diseases named collectively _____ caused by mutations in K+, Na+, Ca2, and Cl- channels that are known to exist in human and animal models.
channelopathies
once a pore is oen, a few thousand ions pass through the channel per millesecond
example of gating
most ion channels exist in one of three possible configurations, which is regulated by various stimuli.
open, closed, inactivated
The ease whith which an ion can go through a single channel
ionic permeability
voltage gated channels fall in what two categories
multimeric, and monomeric
what is a multimeric voltage gated channels
potassium channel
voltage gated monomeric channel
sodium channel
what is the technique of ______ in studying ion channels.
patch clamping
gated channels
regulated, chemically or ligand gated, voltage-gated, mechanically gated,
usually open and allow ions to move back and forth across the membrane without regulation
open channels.
the most biological membranes are impermeable to charged substances, including small ions such as
Na+, K+, Ca2+, and Cl-
A variety of proteins termed
_____ have been identified
ion channels
Most ion channels are highly selective and allow only ___ type of ions to pass through
one
the diffusion of ions through a channel is ____ ____
always down hill, from a high to low concentration
ion channels are ___
bidirectional
how many different ioni channels have been discovered?
75
movement of water readily from hypotonic solution to a hypertonic solution. Many cells are much more water permeable than explained by simple ____ through the bi-layer.
osmosis
proteins that allow the passive movement of water from one side to the other
aquaporins
The hormone _____ stimulates water retention by the collecting ducts of the kidney, by way of these channels
vasopressin
a mutation in this aquaporin channel, in which persons excrete large amounts of urine because their kidneys don’t respond to vasopressin
congenital nephrogenic diabetes insipidus
carries a only one kind of solute across the membrane
uniport
cooperative channel which moves two substances simultaneously in the same directions, e.g. Na+ and glucose. Due to concentration gradient, Na+ moves downhill and releases enough free energy to move glucose uphill.
symport
exchanges one solute for another by transporting them in opposite directions-e.g. Cl- for HCO3
antiport`
In a _______ the transport proteins for cyteine and other amino acids is missing from the membrane
kidney disease, cystinuria
a common form of _____ involves mutations that alter the sequences of transmembrane segments of the transporter preventing transport across the plasma membrane
diabetes
glucose transporters are actually a family of enzymes that transport the _____
6-C sugars
D-mannose Km
20mM
D-glactose Km
30mM
if glucose ratios are high all the ____ are occupied
transporters
D-glucose
1.5mM
l-glucose
> 3000mM
Transport proteins can be ____ by moleules that resemble the solute normally carried (similar to competitve inhibition in enzymes)
ingibited
Transport proteins can be _____ with solute, so a maximum transport rate occurs when all binding sites are occupied with solute
saturated
Transport proteins are ____ for the solutes they transport. There is probably a specific binding site analogous to an enzyme’s active site.
specific
transport protein remains in place in the membrane and translocates solute by alternating between _ confomations
2
term applied to some transport proteins that move uncharged molecules like glucose
permease
proteins that operate in facilitated diffusion are termed _____
transport proteins
transport proteins were formerly nown as
carrier proteins
_____ is the movement of a molecule across a membrane by the aid of a protein that does not just form a channel but instead binds the ligand and undergoes a conformational change delivering the molecules across the membrane.
facilitated diffusion
larger polar molecules such as sugars, amino acids, and phosphorylated intermediates have____ membrane penetrability
poor
factors that affect the simple diffusion of a molecule
partition coefficient, size,
a measure of the polarity (or nonpolarity) of a substance
partiton coefficient
rate of movement through a membrane depends on the compounds
size
very small uncharged molecules penetrate a membrane very quickly like
O2, CO2, NO, H2O
GLUT1
glucose permease
transport protein remains in place in the membrane and _____ solute by alternating between 2 conformations
translocates
transport protein might bind to solute in one ____ and deposit it on the other side of the membrane in another conformation
conformation
diffusion is the principle used in what lab technique
dialysis
two categories for diffusion
passive and active
____ tells if a reaction can thermodynamically happen, but doesn’t say that it will happen! Rate of a reaction is a function of specialized enzymes.
delta G
Molecules that ____ react with one another often ___ ____ because they lack sufficient energy.
should, do not
What does a reaction need to react.
delta G, and enough energy to reach Ea
The rate of an enzymatic reaction is _____ to the fraction of molecules that have and energy content >= Ea
proportional
Therefore, the rates of uncatalyzed reactions in cells are very ____.
slow
life depends on the high Ea to ______ cellular reactions from happening at appreciable rates _____ in the presence of a suitable catalyst
prevent, except
protein catalysts are called
enzymes
RNA catalysts are called
ribozymes
three basic properties of catalysts
- increase rate of reaction by lowering Ea requirements
- Catalysts act by forming transient intermediate complexes with substrate molecules and thus position them in a manner that facilitates their interaction.
- catalysts chg only the rate at which equilibrium is reached; no effect on the position of the equilibium
Every enzyme contains, somewhere within its 3 prime structure, a characteristic cluster of amino acids forming an ______
active site.
the location or domain on which the enzymes structure where the actual catalytic action occurs.
active site
Amino acids most commonly found at active sites
cysteine, histidine, serine, aspartate, glutamate, lysine
ion groups that are integral parts of enzyme structure
prosthetic groups
if a _____ is present the reaction occurs about 1x10^9 X faster that if uncatalyzed
catalase
enzymatic catalysis equation
E+S –> E+P
maintain a narrow range of cellular temps
homeotherms
organisms that live in an environment with a higher than average temperature for biotic life such as bacteria that thrive in environments that average 70 degrees C
thermophiles
most enzymes are ____ sensitive
pH
enzyme environmental requirements
sensitivity to temperatures, sensitivity to pH , sensitivity to ion concentration,
the number of substrate molecules converted to product per unit time
turnover rate
the presence of an enzyme in a cell ______ tgat a given reaction will occur ata rapid rate unless cellular conditions are favorable for enzyme to function
may not ensure
what is much of our understanding of the hyperbolic relationship between [S] and v is owed to two German enzymologists;
Lenor Michaelis and Maud Mentan.
michaelis-mentan equation
v=vmax[S]/(Km+[S])
very low substrate concentration Mand M equation
v=Vmax[S]/Km
High substrate concentration
V=Vmax
at a very high [s] the velocity of an enzyme-catalyzed reaction is _____ of changes in [S] and is therefore approximately constant
independent
the maximum velocity, or upper limiting value, to which v tends as [S] approaches infinity.
Vmax
substrate concentration equals Km=[S]
v=(1/2)Vmax
__ is the specific substrate concentration at which the reaction proceeds at 1/2 its upper limit (Vmax)
Km
the value of Km is termed the ________ ___
michaelis constant
Enzymes that have a low Km for a specific substrate are said to have a ____ for that substrate.
high affinity
example of a double reciprocal plot
lineweaver-Burk equation
lineweaver-burk y intercept=
1/Vmax
lineweaver-burk x-intercept=
-1/Km
lineweaver-burk slope=
Km/Vmax
Enzymes are influenced by the presence of many groups of molecules.
poducts, alternative substrates, substrate analogues, toxins, drugs, allosteric effectors
usually bind to the enzyme covalently, causing irrevocable loss of catalytic activity
irreversible inhibitors
irreversible inhibitors is represented as
E+I ->->EI
inhibitor binds to an enzyme in a dissociable manner, such that the bound and free forms of the inhibitor exist in equilibrium with each other
reversible inhibitors
Reversible inhibitors can be represented as
E+I EI
competes with substrate for binding at the active site but cannot be catalyzed
competitive inhibitors
term applied to chemicals designed to closely resemble a substrate so they bind at an enzyme’s active site while being uncatalyzable. Recall GTP-analogues used to study Dynamin and other GTPases
substrate analogues
do not bind at the enzyme’s active site, bind at another location on the enzyme, not usually at an allosteric site, binding location maybe an unpredictable location on the enzyme surface
Noncompetitve Inhibitors
binds to ES complex prevents catalysis, substrate is still taken up from the environment but is locked in an ES form
uncompetitive inhibitors
those mechanisms that depend directly on substrate-enzyme interactions are termed
substrate-level regulation
substrate regulation
pH, [S], inhibitors, temp
enzymes regulated exist in 2 different shapes, in one form the enzyme has a high affinity for substrate…. high reaction rate
allosteric regulation
In addition to an ___ ___ many enzymes have an _____ ____ located on the _____ ___, at which effectors can bind and alter the shape of the enzyme.
active site, allosteric site, allosteric domain,
catalyzes this reaction and is inhibited by its own product G-6-P . If G-6-P accumulates hexokinase is inhibited slowing down the further entry of glucose into the pathway.
hexokinase
almost invariably, enzymes at first or early steps of a multi-step pathways are regulated allosterically.
feedback inhibition
5 common enzyme regulation methods
substrate regulation, allosteric regulation, property of cooperativity, covalent modification, proteolitic cleavage
binding at one site increases the affinity for substrate at other sites
positive cooperativity
binding at one site reduces the affinity for the substrate at other sites
negative cooperativity
in this form of regulation, the activity of an enzyme is affected by the addition or removal of specific functional groups
covalent modification
enzymes that catalyze the phosphorylation of other molecules
kinases aka phosphorylases
most often involves the transfer of the phosphate group from ATP to the hydroxyl group of a
serine, threonine, or tyrosine
enzymes that catalyze the process of removing a phosphate, i.e. catalyze dephosphorylation
phosphoprotein phosphatses
The breakdown of glycogen in skeletal muscle cells is catalyzed by ______ ____.
Glycogen Phosphorylase
How is glycogen phosphorylase kinased?
phosphorylase kinase
memorize the cyclic AMP
chp 6
this type of activation involves the one-time, irreversible removal of the polypeptide chain by an appropriate proeolytic enzyme
proteolytic cleavage
each of these is produced in an inactive form termed a ____ ____
zymogen or proenzyme
inactive zymogens have modified names….. ____ whatever or whatever-_____
pro-, ogen
An indicator of the first molecular event during Experimental Pancreatitis
TAP
TAP stands for
trypsin activation protein
oxidation-reduction reaction
oxidoreductases
transfer of functional groups from one molecule to another
transferases
hydrolytic cleavage of one molecule into two molecules
hydrolases
removal of a group from, or additionof a group to, a molecule with rearrangement of electrons
lyases
movement of a functional group within a molecule
isomerases
joining of two molecules to form a single molecules
ligases
