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METABOLISM
all the chemical reactions that occur within a cell
ANABOLIC
Increase in molecular order; decrease in local entropy
ANABOLIC
Pathways that produce cellular components
ANABOLIC
Synthesize polymers in order to store energy
Endergonic
energy requiring reaction
Exergonic
energy liberating reaction
CATABOLIC
Pathways that breakdown cellular components
CATABOLIC
Decrease in molecular order; increase in local entropy
CATABOLIC
Release free energy; produce small molecule building blocks
exergonic
ATP Hydrolysis is Highly _____
Respiration
The flow of electrons, either through or within a membrane, from reduced coenzymes to an external acceptor, usually accompanied by the generation of energy in the form of ATP
36 atp
total net ATP yield from complete oxidation of substrate (glycolysis and respiration)
Mitochondria
perform most of the cellular oxidation reactions and produce the bulk of the ATP produced in an animal cell.
IMM
surrounds the innermost space, the matrix and forms the cristae of the mitochondria
Cristae and Matrix
the major working parts of the mitochondria
electrochemical gradient
drives H+ back into the matrix where the force is harnessed to produce ATP and for selective transport of metabolites across the IMM.
Fusion
rescues stress by allowing functional mitochondria to complement dysfunctional mitochondria by diffusion and sharing of components between organelles.
Hyperfusion
Stress-induced ___________ yields maximal potential, whereas under relaxed conditions cells are able to segregate the damaged ones.
Fusion/Fission
Allows redistribution of mitochondria throughoutthe cell.
Fusion/Fission
Maintains healthy mitochondria.
Fusion/Fission
Plays prominent roles in many disease related processes (apoptosis, mitophagy, etc.)
Mitochondrial Matrix
Almost void of non-coding DNA, variation in genetic code, relaxed codon usage
Mitochondrial Matrix
has a high protein concentration
Mitochondria
Generates reducing power and carbon building blocks for cellular growth, Performs two critical steps in the urea cycle, Adapting metabolic pathways to different nutrient conditions, Membrane biosynthesis, Calcium buffer system.
Proton Motive Force (PMF)
form of potential energyconsisting of charge (Δψm) and chemical (ΔpH)components, that together drive ATPproduction
TCA Cycle
Oxaloacetate → x3 NADH, x1 FADH2 → Oxaloacetate
3, 1
TCA produces __ NADH and __ FADH2 from one pyruvate
2, 2, 2
Glycolysis produces __ pyruvate, __ NADH, and __ ATP from one glucose
8, 2, 4
Glycolysis + TCA produces __ NADH, __ FADH2, and __ ATP
Redox Potential
a Measure of Electron Affiliates
7
NADH produces enough energy to make __ molecules of ATP by donating electrons to diatomic oxygen
1 Electron
Cytochromes and Iron-Sulphur Clusters carry _________
Quinones
These electron carrying cofactors can carry up to two electrons at a time
Quinones
Coenzyme Q and Ubiquinone are examples of these E- Carrying Cofactors
phobic
Coenzyme Q is hydro____
NADH Dehydrogenase (Complex 1)
Largest of the respiratory enzyme complexes. Accepts electrons fromNADH and passes them to ubiquinone.
NADH Dehydrogenase (Complex 1)
Reduces Ubiquinone to Ubiquinol to oxidize NADH to NAD+
NADH Dehydrogenase (Complex 1)
takes in 6H+ and pumps 4H+ out
Succinate Dehydrogenase Complex (Complex 2)
Oxidizes a molecule of succinate to fumarate to generate reduced ubiquinone
Cytochrome c Reductase Complex (Complex 3)
Completely REDUCES Cytochrome C – picks up electrons
Q Cycle
2 Ubiquinol + 2 Cytochrome C³+ + 2 H+ (in) → 2 Ubiquinone + 2 Cytochrome C²+ + 4 H+ (out) (+ 1 ubiquinol??)
Cytochrome c Oxidase Complex (Complex 4)
Completely OXIDIZES Cytochrome C – gives away electrons
Cytochrome c Oxidase Complex (Complex 4)
4 Cyt C²+ + 8H+ (in) + O2 → 4 Cyt C3+ + 2 H2O + 4H+ (out)
Proton Pumps
conformational change transporting H+ from the matrix to the IMS
Asp, Glu, Ser, Thr
These 4 amino acids serve as proton wires
Reactive Oxygen Species (ROS)
chemically reactive chemical species containing oxygen
Superoxide (O2-)
product of the one-electron reduction of dioxygen O2
Superoxide (O2-)
Reduction in the NADH pool, Reverse Electron Transport, and Normal mitochondria activity all lead to production of:
8000, 400
ATP synthase works at ____ RPM, and produces ___ molecules of ATP per second
ATP Synthase
The c Subunits of ___ _______ determines proton usage per molecule produced
dimerization
__________ of ATP synthase is required for proper cellular respiration
ETC
contains three respiratory enzyme complexes through which electrons pass on their way from NADH to O2.
NADH, Succinate, Ubiquinone, Cytochrome C, Oxidase
NADH → ______ Dehydrogenase Complex → _______ Dehydrogenase → _________ (Coenzyme Q) → __________ Reductase → Cytochrome c → Cytochrome c ______ → ATP + H20 + O2
H+
flows back into the matrix through ATP Synthase, providing the basis of ATP production in the cell.
Endocrine Signals
Long range signal produced at distances from their target and carried by the circulatory system to the site of activation (e.g. Hormones)
Paracrine Signals
Short range signal produced locally andreach their target by diffusion to nearby tissues (e.g. Growth Factor)
Juxtacrine Signals
signals that require physical contact between sending and receiving cell
Autocrine Signals
signaling in which sending and receiving mediators are located on the same cell
Ligands
signaling molecules that trigger a signal cascade by bindingto receptor proteins
Receptors
proteins responsible for detecting stimuli
Signal Transduction
The ability of a cell to translate receptor-ligand interactions to change cellular behavior or gene expression.
Primary Messenger
ligand that initiates the signal cascade by binding to the initial receptor protein
Second Messenger
additional molecules in the cell that receive and relay the signal from one location to the next
Ligand Binding
Receptor conformation changes, clustering, or BOTH, cause this
Pre-Programmed Response
a predetermined sequence of events that occur within a cell depending on specific ligand binding to a receptor.
Dissociation Constant (Kd)
amount of ligand needed to produce a state where exactly half of the receptors are occupied (107 – 1010nM)
agonists
ligands that bind to their receptors and activate a signaling cascade.
Antagonists
ligands that bind to receptors and prevent naturally occurring messengers from binding and activating the receptor.
Signal Amplification (Upregulation)
The strong response of a target cell to the signaling cascade initiated by ligand binding to its receptor.
Downregulation
one method of this is to reduce the concentration of free ligand available to the receptor (neurons/neurotransmitters)
Neurotransmitter Reduction
Preventing reuptake of neurotransmitter at neuronal synapses
Downregulation
one method of this is to reduce the amount of receptor or the sensitivity of the receptor for the ligand (Receptor desensitization)
Receptor Desensitization
cells in general are geared to sense CHANGES in ligand concentrations rather than fixed ligand concentrations
G proteins
guanine nucleotide binding proteins
Amino terminus
located in extracellular space and location of unique ligand binding sites in G-protein coupled receptors
Carboxy Terminus
located in cytosol and location of unique specific G-protein binding sites in G-protein coupled receptors
G Protein Coupled Receptor Kinases (GCRKs)
enzymes that phosphorylate GPCRs affecting their ability to interact with G-proteins
Large Heterotrimeric G proteins
These proteins are activated by G protein-coupled receptors and are made up of alpha (α), beta (β) and gamma (γ) subunits, the latter two referred to as the beta-gamma complex.
small monomeric G proteins
These proteins are homologous to the alpha (α) subunit found inheterotrimers, but exist as monomers. (e.g. Ras)
Regulators of G Protein Signaling Proteins (RGSs)
proteins that stimulate the catalysis of GTP hydrolysis by G-alpha protein subunits.
Acetylcholine (Ach)
In the absence of _________, aG proteins associated with the _________ receptor is bound to GDP and inactive. (same term)
acetylcholine (Ach)
Upon binding of ______, the G protein is activated by dissociation of G-alpha and the G-beta-gamma complex. The G-beta-gamma complex subunit interacts with a K+ ion channel causing it to open.
signaling cascades
Depending on situation, BOTH G and G/ can result in the initiation of ______ ________
Primary
________ messengers are often hydrophilic or charged in nature
Second Messengers
molecules that relay signals received at receptors on the cell surface — such as the arrival of protein hormones, growth factors, etc. — to target molecules in the cytosol and/or nucleus. (e.g. cAMPand Ca+2)
This second messenger propagates signal from extracellular messengers which cannot pass through the plasma membrane
cAMP
This second messenger regulates ion channel function and is involved in the activation of downstream protein kinases
Gs
Adenylate Cyclase Stimulatory Protein Coupled Receptor
Phosphodiesterases
cAMP molecules in the cytosolare hydrolyzed to AMP by ___________
cAMP, phosphodiesterase
PKA activity can be increased by increasing ____ production or blocking _________
extracellular signals
All cells communicate through ___________ _________ that initiate signal transduction pathways
calcium ions
The concentration of ______ inside a cell can act as an “on v. off switch” for many different cellular processes
Ligand-Receptor
______—_______ interactions are very similar to enzyme-substrate interactions.
G-Protein Coupled Receptors (GPCRs)
coupled to trimeric G proteins. Interaction causes conformational changes that switch the G protein complexes “on” or “off” depending on their interactions with GDP/GTP
G-Protein Coupled Receptors (GPCRs)
can regulate ion channels and control the in flow of ions into the cytosol of the cell.
adenylyl cyclase, cAMP
Ligand binding of GPCRs can activate Gs-alpha and result in the activation of ______ ______ which converts ATP to _____.
cAMP
binds to the regulatory subunit of protein kinase A (PKA) releasing the catalytic subunits which mediate diverse effect in most cells.
Tyrosine Kinases
phosphorylate Tyrosine (Y) residues
Serine/Threonine Kinases
phosphorylate Serine (S) and/or Threonine (T) residues
Dual Specificity Kinases
phosphorylate Serine (S) or Threonine (T) residues AND Tyrosine (Y)