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24 Cards in this Set
- Front
- Back
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What is the PPP?
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AKA: "Hexose monophosphate shunt"
Used to: 1) make NADPH for reductive biosynthesis as an anti-oxidant 2) produce RIBOSE-5-PHOSPHATE to make nucleotides! |
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What pathways require NADPH?
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(produced by PPP)
NADPH used to make: 1) FAs 2) Cholestrol 3) Neurotransmitters 4) Nucleotides Also, REALLY important in detox-- 1) Reduction of glutathione 2) Cytochrome p450 monooxygenase |
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What tissues use the PPP?
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ADRENAL GLAND, LIVER (big ones)
testes, adipose, ovary, mammary gland, RBC's |
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What are the steps in the PPP?
(well, the ones we need to know) |
G-6-P--(G-6-PDH-makes NADPH)-->6-PHOSPHOGLUCONO-LACTONE--(lactonase)--6-PHOSPHOGLUCONATE--(6-phosphogluconateDH--makes NADPH)-->RIBULOSE-5-P
-->after this step, there are TONS of reactions using carbon intermediates-->end up generating F-6-P and G-3-P-->GLYCOLYSIS -->So, overall, w/PPP, you generate RIBOSE-5-P (nucleotide synthesis) and GLYCOLYTIC INTERMEDIATES--nothing is wasted! |
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How are the PPP enzymes regulated?
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G-6-PDH
-->catalyzes rate limiting step -->ACTIVATED by..insulin Both of these reactions produce NADPH-->makes sense-->when insulin is HIGH, you want to make sure you have enough reducing power to catalyze FA (and sterol) synthesis! |
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What is G-6-PDH deficiency?
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-->Oxidations in your body generate tons of peroxide compounds (H202, RO-OH)-->generate OH radicals-->damage tissue.
-->catalase and GLUTATHIONE PEROXIDASE neutralize these compounds... GSH + ROOH-->GSSG + H2O +ROH (glutathione peroxidase rxn) **So, glutathione is OXIDIZED in the reaction and needs to be regenerated to continue neutralizing compounds. -->GLUTATHIONE REDUCTASE uses NADPH to reduce/regenerate glutathione for another neutralizing rxn... GSSG + NADPH + H-->2GSH + NADP (glutathione reductase rxn) -->G-6-PDH generates NADPH during the PPP. -->No G-6-PDH=NO NADPH=No glutathione reductase rxn=NO regenerated glutathione! -->leads to: increased OH free radicals and tissue damage. -->Also, damages RBC's-->causes hemolytic anemia! |
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Why is G-6-PDH sometimes not so bad?
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-->G-6-PDH leads to increased presence of toxic OH compounds in the cell.
-->damage tissue but also CONFER RESISTANCE to malaria (odd..) |
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What is beri beri?
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-->THIAMINE deficiency
-->Transketolase (used in PPP) uses TPP as a cofactor. -->TPP can't work w/no thiamine-->no PPP! |
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What is gluconeogenesis?
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-->synthesis of glucose from non-carb precursors
-->produces glucose that can be released into blood during times of low glucose (overnight fast, high protein/fat diets, exercise). -->glucose used by: -Brain (only glucose can cross BBB)** -RBC (entirely dependent)** -muscle (during exercise a little) **=tissues that can't use FA's generated by b-oxidation during fasting. |
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In gluconeogenesis increased or decreased in diabetics?
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WAY increased-->why they have such ridiculous hyperglycemia!
--Don't have any insulin--never gets turned off! |
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What are the steps in gluconeogenesis?
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PYRUVATE--(**pyruvate carboxylase)-->OAA--(**PEPCK)-->PEP--(**enolase)-->2-PHOSPHOGLYCERATE--(phosphoglycerate mutase)-->3-PHOSPHOGLYCERATE--(phosphoglycerate kinase)-->1,3 BISPHOSPHOGLYCERATE--(G-3-PDH)-->G-3-P
G-3-P--(triose phosphate isomerase)-->DHAP G-3-P+DHAP--(aldolase)-->F-1,6-bisP--(**F-1,6-bisPase)-->F-6-P--(phosphoglucose isomerase)-->G-6-P--(**G-6-Pase)-->GLUCOSE **--different than glycolysis enzymes |
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What are the precursors to gluconeo?
Where do they enter the pathyway? |
Precursors:
1) Lactate 2) Glycerol 3) A.Acids (Alanine) Lactate-->Pyruvate Glycerol (from TAG hydrolysis)-->DHAP A.Acids-->Pyruvate, OAA |
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If the pyruvate kinase step (glycolysis) is irreversible, how the heck does Pyruvate-->PEP in gluconeogenesis?
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-->It uses TWO enzymes
Pyruvate Carboxylase Pyruvate-->OAA PEPCK OAA-->PEP Pyruvate carboxylase-->needs ATP PEPCK-->needs GTP -->Both rxns require energy (generated from b-oxidation) -->In addition, pyruvate carboxylase is a BIOTIN requiring enzyme. PC binds biotin-->Biotin binds lysine-->lysine+biotin bind CO2 **CO2 will NOT bind biotin unless Acetyl CoA is present (generated from B-oxidation)--IMPORTANT |
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Why is liver the only tissue that can really do gluconesis?
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-->It has G-6-Pase!
-->Muscle and other non-gluconeogenic tissues lack this enzyme-->cannot release free glucose. |
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Describe compartmentalization of gluconeogenic generation of OAA
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PYRUVATE CARBOXYLASE reaction (Pyruvate-->OAA) occurs in the mitochondria.
-->After being made, OAA needs to get into the cytosol where the other gluconeo enzymes are located--> can not cross the mitochondrial membrane to undergo the rest of gluconeogenesis. -->Must be converted to malate-->shuttled out of mitochondria-->converted into OAA+NADH-->ready for PEPCK reaction! **OAA can also be converted to aspartate and pushed across membrane. However, not ALWAYS the case.. -->In humans, there is sometimes a mitochondrial PEPCK, which generates OAA-->PEP in one step, circumventing the need for the OAA shuttling. |
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Describe compartmentalization of G-6-Pase.
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-->G-6-Pase is located in the ER.
-->several possible reasons: 1) isolate it--prevent competing reactions 2) release glucose in "packets" |
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Describe hormonal regulation of gluconeogenesis
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G-6-Pase and PEPCK
ACTIVATED by..glucagon, epinephrine, cortisol INHIBITED by..insulin |
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Describe PEPCK promotor
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-->PEPCK is an INDUCIBLE enzyme.
-->contains cis-acting elements that bind CREB and GRE-->ACTIVATE transcription of more PEPCK -->bind IRE-->inhibit PEPCK transcription. -->IRE is insulin-regulated transcription factor-->will INHIBIT PEPCK transcription when high -->So, when insulin is low, PEPCK can be made! From BRS--"Transcription of gene encoding PEPCK is stimulated by binding of proteins phosphorylated by cAMP and glucocoritcoid-protein complexes" (CREB?) |
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Describe allosteric regulation of gluconeogenesis (compared to glycolysis)
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GLUCONEOGENESIS
PYRUVATE CARBOXYLASE (pyruvate-->OAA) ACTIVATED by..Acetyl CoA INHIBITED by..ADP PEPCK (OAA-->PEP) INHIBITED by..ADP F-1,6-BisPase (F-1,6-BisP-->F-6-P) ACTIVATED BY..citrate INHIBITED by..AMP, F-2,6-BisP (hormonal control) |
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Describe the Cori Cycle
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RBC-->release lactate
Muscle-->releases lactate and pyruvate -->pyruvate/lactate can go to liver for gluconeogenesis -->Where does resulting glucose go? mainly, to RBC-->Low insulin means low glut-4 transporters in muscle, so less glucose can get in. |
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Why is the muscle releasing pyruvate/lactate during fasting/exercise?
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-->There is too much pyruvate present. Supply of pyruvate from glycolysis OUTSTRIPS the muscle's ability to use it! (in TCA; etc)
--Also, PDH (pyruvate-->acetyl coa) may be inhibited due to INCREASED acetyl coa from b-oxidation. --As exercise is prolonged, we burn more fat and less glucose-->b/c elevated citrate inhibits PFK-1-->increased G-6-P-->inhibited hexokinase |
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Describe the Alanine cycle.
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-->Alanine released (derived from proteolysis and pyruvate) from muscle-->travels to liver for gluconeogenesis
-->Liver makes glucose that really isn't used by muscles--used by "needier" tissues--RBC's, brain--muscle uses B-oxidation and ketones. |
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What are some deficiencies/diseases in gluconeogenesis?
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1) G-6-Pase deficiency
-->get lactic acidosis, fatal hypoglycemia. 2) F-1,6-BisPase deficiency -->get lactic acidosis, fatal hypoglycemia1 |
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Describe effects of ethanol (booze) ingestion on gluconeogenesis
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-->Catalyzes following rxn:
Ethanol + NAD-->Acetaldehyde+NADH -->acetaldehyde damages the liver. -->Increased NADH inhibits TCA cycle, b-oxidation and activates lipogenesis -->increased NADH favors lactate production-->lactate is shunted into alternative rxn pathway-->not available as gluconeo precursor-->less gluconeogenesis. -->decreased b-oxidation=decreased acetyl coa-->can't activate pyruvate carboxylase-->less gluconeogenesis from pyruvate -->get lactic acidosis and hypoglycemia Shows links b/w b-oxidation and gluconeo: b-oxidation makes NADH-->stimulates pyruvate carboxylase->stimulates gluconeo NAD-->stimulates b-oxidation and TCA cycle-->makes energy |
