Biochem Weight Loss Carbohydrate metabolism continued
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refresher
Describe all of glycolysis, start with glucose - Glucose->G6P->F6P (note: facilitates GKRP-glucokinase) -> F16P (takes ATP) -> GAP3 and DHAP -> 1,3bisphosphoglycerate (makes NADH)-> 3phosphoglycerate (makes ATP) ->2phosphoglycerate ->phosphoenolpyruvate -> pyruvate (makes ATP) -> lactate (regenerates NAD)
- how many ATP/NADH do you get out per glucose in glycolysis
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2 ATP total (2 used four made)
2 NADH
regenerate NAD through lactate dehydrogenase, also through TCA cycle(really through malate aspartate shuttle system so get NAD right away) -
describe the malate aspartate shuttle
FIRST HALF, getting malate in -
NADH transfers electrons to oxaloacetate forming malate
malate crosses into mito via malate/alpha-ketoglutarate antiport
malate gives up electrons to NAD forming oxaloacetate -
malate aspartate shuttle
SECOND HALF, getting oxaloacetate out -
oxaloacetate is transaminated to aspartate
(this is done through glutamate turning into alpha-ketoglutarate)
aspartate is transported out of the mito via a glutamate/aspartate antiport
aspartate is then change into oxaloacetate (from alphaketoglutarate going to glutamate)
SEE PAGE 27, look i SAY - build up of what inside the mito drives malate inside?
- alpha-ketoglutamate
- build up of what outside the mito drives aspartate out?
- glutamate
- how else can you get NADH inside?
- glycerol 3-phosphate shuttle
- glycerol 3-phosphate shuttle
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nadh gives electrons to dihydroxyacetone phosphate (DHAP) making glycerol-3-phosphate
glycerol-3-phosphate hands off electrons to membrane mito deH changing FAD to FADH2 (g3p goes back to DHAP)
FADH2 hands off to Q which can then enter the respiratory chain - how do yeast deal with anaerobic respiration
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pyruvate-> acetaldehyde
->ethanol (makes NAD) - what is the commitment step for glycolysis
- PFK1
- how is PFK 1 negatively regulated
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allosteric regulation:
Negative: ATP (binds catalytic site), 3-phosphoglycerate, phosphoenolpyruvate, citrate(muscle), phosphocreatine(muscle), H+, lactate - how is PFK1 positively regulated
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AMP
ADP
F6P (binds catalytic)
F2,6P - see page 30 for the effects of substrate concentration (of ATP and F6P each) on the velocity of the PFK reaction
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ATP - for ATP: first it rises then it declines, this is because ATP is a subtrate for the reaction, but is also a negative inhibitor
F6P is sigmoidal showing positive cooperativity; the more F6P, the faster the rxn goes - PFK and ATP
- atp is a substrate, but it also affects F^P binding and therefore is a neg heterotropic effector
- what type of regulation is ATP on PFK reaction (hint: not looking for "negative regulation")
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a K-type regulation: substrate binding is affected, not Vmax
has no allosteric effect as a binder of the catalytic site, but is a negative allosteric effector in interfering with F6P - the relaxed state of PFK1 has a high affinity for what?
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F6P
F2,6P
AMP - the taut state has a high affinity for what
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ATP
Citrate - Describe PFK2, in liver, heart and skeletal muscle, specifically what is phosphorylated
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F2,6P is syn'd and degraded by an enz which has both a kinase and phosphatase activity
the kinase activity is PFK2?
Phosphorylation of PFK2 is inhibitory and controlled by PKA (which as we know is regulated by cAMP)
epi in heart stimulates glycolysis
glucagon in liver supresses glycolysis - what does f2,6bP do?
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makes PFK1 sensitive to regulation by glucagon
and inhibits F1,6Pase
is the key allosteric regulator of PFK1 - PFK2 in liver and heart, what does phosphorylation of this enzyme do in each
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hormones->increase cAMP->increases PKA, which phosphorylates PFK2,
P-PFK2 in heart inhibits phosphatase, so kinase is active and F6P goes to F26P which stimulates PFK1 and therefore glycolysis
P-PFK2 in liver has the kinase inhibited so the phosphatase works. this decreases F2,6P so it cant stimulate PFK1 so - liver and heart PFK 1 are mainly effected by F2,6P, what are the rest of tissues positively effected by?
- AMP
- will high blood sugar increase or decrease F2,6P in the liver? in the heart?
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it will increase F2,6P thereby increasing glycolysis in times of plentiful sugar
glucagon->increase cAMP->PKA->p-PFK2(phosphatase active)->low F2,6P and low PFK1 activity
in the heart it is stress that activates PKA, not blood sugar, high stress = increase glycolysis = increase F26P - will stress increase or decrease F2,6P
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increase
epi increases cAMP->PKA-> P-PFK2(kinase active)->F26P active
glucagon ->increase cAMP-> - MOVING ON
- oiuft
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PYRUVATE KINASE
positive and negative effectors -
in liver it is an allosteric enzyme
positive: F1,6bP
PEP
negative: ATP - See biochem carbs 1 slides 31-38
- DO IT
- List the four tissue specific isozymes of pyruvate kinase
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L- in liver and kidneys
R - in RBC
M1 - heart brain muscle
M2 - all remaining tissues
note: M2 muscarinic receptors in heart
M1/3 muscarinic receptors in all other tissue
muscarinic receptors are found as end organ receptors of parasymp, inhib by atropine -
L and R pyruvate kinase isoforms, explain the gene
transcriptional
post transcriptional
tranlational
post translational -
TRANSCRIPTIONAL
same gene, different promoters, = different amino termini
L has a tata box - contains serine residue at 11
R has a CAAT box - no serine residue at 11 - M1 and M2 explain gene processing
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post transcriptional
ALTERNATE SPLICING
RNA editing