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34 Cards in this Set

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