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79 Cards in this Set
- Front
- Back
What is the term that describes the mechanism by which one cell (the sender) sends a message to change the function of another cell (the target)?
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Intercellular signaling
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What is the term that describes the decoding of the signal by the target which ultimately results in altered function?
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Intracellular signaling
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What are the two mode of intercellular signaling?
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Juxtacrine and secreted molecules
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What term describes the type of signaling that occurs between two cells when in direct contact with eachother?
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juxtacrine
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What term describes the intercellular signaling that occurs when signal molecules travel through extracellular space to reach the target?
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secreted molecules
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What term describes when cells communicate through gap junction channels that allow direct transfer of small ions or metabolities between neighboring cells?
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juxtacrine signaling
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What term described when a protein expressed on the surface of a sender interacts with the receptor expressed on the surface of the neighboring target?
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juxtacrine signaling
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What are the four types of secreted molecule signaling?
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endocrine signaling, paracrine signaling, synaptic signaling, autocrine signaling
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What type of signaling occurs when glandular tissue synthesize and secretes hormones into the bloodstream to act on targets anywhere in the body?
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Endocrine signaling
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Do all cells respond to endocrine signaling?
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No, all cells will be exposed to the hormone, but only specific target cells will respond
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What levels are the hormones at in the blood in endocrine signaling?
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Very low levels (picomolar-nanomolar); so receptors must have a high affinity yielding slow onset and long duration
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What type of signaling does the sender cell secrete signaling molecules into the immediate local environment via passive diffusion to reach their destination?
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paracrine signaling
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What is the concentration and affinity of the signal molecules in paracrine signaling?
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nanomolar-micromolar / lower affinity so the signal lasts a shorter duration
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What term describes when the same cell is the sender and the target of signaling?
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autocrine signaling
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Where is autocrine signaling found?
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immune and inflammatory responses
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What is the affinity and concentration of the signal molecules in autocrine signaling?
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same as paracrine - high concentration (nanomolar - micromolar) / lower affinity so the signal lasts a shorter duration
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What molecules can be the secreted signaling molecules?
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Proteins, glycoproteins, small peptides, amino acids, amines, lipids, fatty acids, steroids, nucleotides, nucleosides, gases
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What are the four major superfamilies of cell surface receptors?
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Ligand-gated ion channel, enzyme-linked, cytokine, and g-protein coupled receptors
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What is the mechanism of operation for the nicotinic acetylcholine receptor?
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The Nicotinic acetylcholine receptor is an example of a ligand-gated ion channel receptor. When the neurotransmitter acetylcholine binds, the receptor is ligand bound allowing a channel to form. After one millisecond, the receptor becomes desensitized and changes to an inactive conformation even if the ligand remains bound. The channel will not reset to the basal state until the ligand is removed by either dissociation or acetylcholinesterase cleaves it into acetate and choline
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What is the mechanism of operation for the insulin receptor?
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Insulin binding to the extracellular alpha subunit causes autophosphorylation of a Tyr on the intracellular beta subunit. This stimulates phosphorylation of some proteins and dephosphorylation of other proteins
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What type of activity do enzyme linked receptors have?
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intrinsic catalytic activity. Regulate long term cell functions through gene expression (insulin receptor)
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Do cytokine receptors contain intrinsic enzymatic activity?
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NO, bu do trigger enzymatic activity intracellularly
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What does cytokine binding cause in cytokine receptors?
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Can cause a conformational change in the receptor which recruits soluble Janus tyrosine kinase (JAK). JAKs recruit and activate signal transducers and activators of transcription (STATs)
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What is the mechanism of operation for the G-protein coupled receptor?
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Agonist binding causes GDP to be released from the alpha subunit. GTP which is abundant in the cytosol binds to the alpha subunit, thereby triggering dissociation. The alpha subunit is soluble and travels to its appropriate effector. The beta and gamma subunit remain membrane associated and bind to their effectors
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How many subunits does a g-protein coupled receptor have and how many transmembrane spanning domains?
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one subunit and 7 alpha helical transmembrane spanning domains
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What does each GPCR have on the extracellular side?
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N-terminus and 3 loops
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What does each GPCR have on the intracellular side?
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C-terminus and 3 intracellular loops
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What is the inactivate state like for GPCRs?
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the heterotrimeric G protein is bound intracellularly to the receptor and also to GDP
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What do the extracellular loops of the GPCR determine?
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what ligand binds
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What do the intracellular loops of GPCR determine?
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what g proteins can bind
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How can a signal be terminated in signal transduction pathways?
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metabolism of the agonist or receptor desensitization
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What is the state described as an unoccupied GPCR with low second messenger level?
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basal state
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What is the state described as a ligand occupied GPCR with high second messenger level?
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Activated state
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What is the state described as GPCR phosphorylates uncoupling from second messenger production?
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Desensitized state
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What are two other names for the citric acid cycle?
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tricarboxylic acid cycle or krebs cycle
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What is the pathway for glycogen to be changed into Acetyl Coa?
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Glycogen --> Glycogenolysis -> Glucose -> Glycolysis -> Pyruvate -> Oxidation -> Acetyl CoA
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What is the pathway for triglycerides to be changed into Acetyl Coa?
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Triglyceride -> Lipolysis -> Free fatty acid -> Beta oxidation -> Acetyl Coa
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What is the pathway for protein to be changed into Acetyl Coa?
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Protein -> Proteolysis -> Amino Acids -> Deamination and oxidation
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What are the possible products of acetyl coa?
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Tricarboxylic acid cycle, ketone bodies, sterols and fatty acids
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Where do the enzymes of oxidative metabolism operate?
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The enzymes of the TCA cycle are located in the mt matrix except succinate dehydrogenase which is bound to the inner mt membrane
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What are the products of one complete TCA cycle and what is the over yield of ATP?
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3 NADH (7.5 ATP), one FADH2 (1.5 ATP), and one GTP (1 ATP). These can yield 10 ATP
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What is the mnemonic for the citric acid cycle?
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Citric Acid Is Obviously Krebs Starting Substrate For Mitochondrial Oxidation
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What does the mnemonic "Citric Acid Is Obviously Krebs Starting Substrate For Mitochondrial Oxidation" mean?
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Citrate -> Cis-Aconitate -> Isocitrate -> Oxalosuccinate -> alpha-Ketoglutarate -> Succinyl-Coa -> Succinate -> Fumurate -> L-Malate -> Oxaloacetate
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What are the five products from the TCA cycle that can act as precursors and what can they form?
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1. Citrate -> Fatty acid and sterols 2. alpha-ketoglutarate -> amino acid synthesis -> neurotransmitters 3. Succinyl Coa -> Heme Synthesis 4. Malate -> Gluconeogenesis 5. Oxaloacetate -> Amino acid synthesis
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What molecules can replenish the TCA cycle?
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fatty acids, alpha keto acids, pyruvate, amino acids
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What odd-chain fatty acids can be formed to Succinyl CoA?
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Propionyl Coa which can be changed to Methylmalonyl CoA which can be changed to Succinyl Coa
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What is a possible fate of Succinyl CoA other than being formed into Succinate?
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Delta-Aminolevulinate
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What ketone body can be utilized to form Succinate from Succinyl Coa?
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Acetoacetate
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Amino acids can be converted to what that can be formed into Acetyl Coa or Oxaloacetate?
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Pyruvate
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Amino acids can be converted to what that can be formed into alpha-Ketoglutarate?
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Glutamate
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What can be used to form Fumarate?
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Various amino acids
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What can be used to form Succinyl Coa? And where does this molecule come from?
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Propionyl Coa can be used to form Succinyl CoA and Propionyl CoA can be derived from Valine and isoleucine
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What amino acid can be used to form oxaloacetate directly?
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Aspartate
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What converts Pyruvate to Oxaloacetate?
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Pyruvate Carboxylase
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What affect does NADH or Acetyl Coa have on the change of pyruvate to Acetyl Coa?
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Negative feedback (on pyruvate dehydrogenase)
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What feedback does Succinyl Coa have upon the conversion of acetyl coa to citrate?
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Negative feedback (on citrate synthase)
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What affect does ATP have on the conversion of Isocitrate to alpha Ketoglutarate? And ADP's affects on the conversion to alpha-ketoglutarate? What enzyme produces this conversion?
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ATP = neg feedback, ADP = positive feedback, enzyme = isocitrate dehydrogenase
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What affect does Ca2, NAHD, GTP, and Succinyl CoA have upon the conversion of alpha-ketoglutarate to succinyl CoA? What enzymes do these factors work upon the produces the conversion?
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Ca2 = positive feedback, NADH = negative feedback, GTP = negative feedback, Succinyl CoA = negative feedback. All work by affecting the alpha KG dehydrogenase
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What is the affect of fluoroacetate on the TCA cycle ?
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It inhibits Aconitase (converts Citrate to cis Aconitate) and is one of the most toxic small molecules known (used in rat poison). Lethal abnormality and therefore not ever seen
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How is ATP formed by the TCA cycle?
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A protonmotive force is developed across the inner mitochonrial membrane. These electrochemical changes and change in pH power the synthesis of ATP
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What are the seven blocks of the electron transport chain?
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Complex I, Complex II, UQ/UQH2 pool, Complex III, Cytochrome C, Complex IV, and complex V
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What is Complex I of the electron transport chain and what does it do?
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Complex I aka NADH-Ubiquinone Oxidoreductase aka NADH dehydrogenase transfers two electrons to flavin mononnucleotide (FMN). The electrons are then transfered one at a time to the Fe S centers and then on to the ubiquinone aka UQ aka coenzyme Q aka CoQ. Transferring these two electrons moves four protons from the matrix side (negative) to the cytosolic side (positive) of the inner mitochondrial membrane
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What is Complex II of the electron transport chain and what does it do?
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Complex II aka Succinate-Ubiquinone Oxidoreductase aka Succinate Dehydrogenase contains flavin adenine dinucleotide (FAD) which gains two protons and two electrons when succinate is oxidized to fumarate in the TCA cycle.
The two protons and two electrons are transferred to UQ; however, there is not enough energy gained to move protons across the membrane. Once ubiquinone is reduced and protonated, it is called ubiquinol |
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What is Complex III of the electron transport chain and what does it do?
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Complex III aka Ubiquinol-Cytochrome c oxidase transfers two electrons to cytochrome c and also transfers two protons to the positive side of the inner mt membrane.
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What is Complex IV of the electron transport chain and what does it do?
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Complex IV aka Cytochrome c Oxidase accepts 4 electrons from cytochrome c and transfers them to oxygen and 4 protons to form 2 waters.
During this process 4 protons are pumped across the mt membrane adding to the protonmotive force available. |
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What is Complex V of the electron transport chain and what does it do?
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Complex V aka ATP Synthase is a molecular motor that is driven by the proton gradient of the inner mt membrane.
Protons flow through the F0 domain and turn the F1 domain. As the g subunit rotates, it changes the conformation of the b subunits. |
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What are the three conformations of the Beta subunits of ATP synthase and what do each of these conformations signify?
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Loose = binds ADP and Pi, tight = forms ATP, Open = Releases ATP
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What is FAD used for?
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Oxidize alkanes to alkenes
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What is NAD+ used for?
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oxidize alcohols to aldehydes or ketones
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What converts acetyl coa to citrate? Is this reaction a pos or neg delta G?
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Negative delta G; citrate synthase
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What converts citrate to cis-aconitate? Is this reaction a pos or neg delta G?
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Aconitase converts Citrate to cis-Aconitate and then to Isocitrate. This reaction is are 0 delta G and thus freely reversible
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What converts Isocitrate to Oxalosuccinate? What is the delta G?
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Isocitrate dehydrogenase; neg delta G
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What converts Oxalosuccinate to alpha-ketoglutarate?
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Isocitrate dehydrogenase
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What converts alpha-ketoglutarate to succinyl coa? Delta G?
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A-ketoglutarate dehydrogenase; negative delta G
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What converts Succinyl Coa to Succinate? Delta G?
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Succinyl Coa synthetase aka succinate thiokinase. Delta g ~ 0
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What converts succinate to fumarate? Delta G?
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Succinate dehydrogenase; delta g ~ 0
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What is the only membrane bound TCA enzyme?
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Succinate dehydrogenase
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What converts Fumarate to L-malate? Delta G?
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Fumarase; delta G ~0
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What converts L-malate to oxaloacetate? Delta G?
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malate dehydrogenase, delta g ~0
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