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34 Cards in this Set
- Front
- Back
Define gluconeogenesis?
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biosynthesis of new glucose, (i.e. not glucose from glycogen).
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Potential substrates for gluconeogenesis?
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pyruvate, lactate, glycerol, and the AA alanine & glutamine
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Describe 1st step of gluconeogenesis, incl enz?
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Pyruvate --> oxaloacetate
Pyruvate Carboxylase |
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Gluconeo. Regulation?
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when ATP or acetyl-CoA [ ] high, pyruvate enters gluconeogenesis
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Can FA be used as gluconeo substrates?
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No
Exceptions: odd-numbered fatty acids |
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Cofactor required in 1st step of gluconeogenesis?
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Biotin, covalently linked to an active site lysine --> cofactor required in carboxylation rx: pyruvate carboxylase
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Gluconeo 2nd step?
ENZ |
Conversion of oxaloacetate --> PEP, PEP carboxylase
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Gluconeo 2nd step: E requirement?
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Lots needed !
•E provided 2 ways: –Decarboxylation is a favorable reaction –GTP is hydrolyzed (equivalent to an ATP) |
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Step 6: Hydrolysis of F-1,6-P to F-6-P
a. Enz b. E c. 2 Inhibitors/1 stimulant |
a. Fructose-1,6-bisphosphatase
b. favorable E [ ] in liver: produces 8.6 kJ/mol c. Allosteric regulation: –citrate stimulates –F2,6-bisphosphate inhibits –AMP inhibits |
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last gluconeo step:
substrate, enz |
Conversion of Glucose-6-P to Glucose
Glucose-6-Phosphatase |
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What make gluconeo possible?
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Presence of G-6-Pase in ER of liver and kidney
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Can muscle & brain do gluconeo.? Why?
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No, do not have G6Pase
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How is glucose release into bloodstream?
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gluc-filled ER vesicles diffuse to the , fuse with plasma membrane & open, releasing glu into blood.
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What happens during rigourus exercise
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buildup of lactate and NADH, d/t O2 shortage & need for more glycolysis
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How is lactate recycled?
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Lactate is returned to liver, & reoxidized to pyruvate by liver lactate dehydrogenase (LDH)
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How is NADH recycled?
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reoxidized to NAD+ during the reduction of pyruvate to lactate
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2 ways gluconeogenesis is regulated?
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Substrate-Level Control: Glucose-6-phosphatase
Allosteric: Fructose-2,6-bisP powerfull neg allosteric effector of 1,6 biphosphatase F-1,6-bisPase is inhibited by AMP, activated by citrate |
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Fate of pyruvate depends on what?
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acetyl-CoA
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What is Glycogen?
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"granules" of high MW
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which enzyme cleaves gluc from non-reducing ends of glycogen?
Whis type of reaction is this? |
glycogen phosphorylase
phosphorolysis (not hydrolysis) |
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Metabolic advantage of glycogen phosphorolysis?
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gluc removed glycogen is in activated state, i.e. phosphorylated and this occurs without ATP hydrolysis
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Describe glycogen:
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Glycogen is a polymer of glucose residues linked by α-(1,4)- and α-(1,6)-glycosidic bonds
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Is muscle glycogen available to other tissues (why or not)
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No, muscled lack gluc-6-phosphatase enzyme
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What other enz is needed to remove gluc residues from the branch points (α-1,6 linkages) in glycogen
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glycogen debranching enzyme
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discuss glycogenolysis regulation by glycogen phosphorylase via confromation change
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Glycogen phosphorylase ( homodimeric enz) R (binds glycogen) or T states
Enz conform.: stim by AMP bind, inhibited ATP or G6P |
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discuss glycogenolysis regulation by glycogen phosphorylase via covalent modification
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ENz modif by +P if gluca binds liver cells, activ. adenylate cyclase --> inc cAMP --> binds cAMP-dep kinase(PKA) --> activ PKA --> glycogenolysis
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Which prot forms the core of glycogen particle
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GLYCOGENin
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In glycogen, what 1st glucose linked to?
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-OH
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WHich enz transfers glycosyl units from UDP-glucose to C-4 hydroxyl at non-reducing end of stand
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glycogen synthase
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On which 2 tissue does glucagon act on? Where is it produced?
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liver and adipose
pancreatic cells |
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Name various type of regulator of glycogen metabolism via glycogen synthase/phosphorylase
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-Allosteric (GP: + by AMP, - by ATP, G6P and caffeine) & (GS: + G6P)
-covalent: GP/GS phosphoralysation Ser residu -horm:glucagon/epi -->adenyl cyclase (via GTP-bind prot) -> cAMP -> activate Kase/Pase control phos GP/GS Pase cascade implfies signal |
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On which 2 organ does epi act on? Where is it produced?
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Muscle and liver
Adrenal glands |
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Effect of insulin on lipid/prot/cho metabolisms? via which process?
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lipid: +lipid synthesis/-lipid breakdown
prot: +prot synthesis and transport/-gluconeogenesis CHO: +glycogen synthesis/glycolysis Via prot phosp/2nd messager |
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Contrast glycogen synthesis factors in liver vs muscle in fed state
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Liver: stim by inhibition of GP by gluc, ATP & G6P, stim of GS by G6P
Muscle: identical except GP not inhibited by G6P, instead by AMP & Ca 2+ |