PDHC regulation by its PRODUCTS Flashcards
Regulation of PDHC is important why?
will have trouble connecting metabolism of sugar to the TCA, this is the only way to get carbohydrade derived pyruvate into the TCA.
NADH and acetyl- CoA compete with what?
Compete with NAD+ and CoA for Active sites on respective enzymes. Essentially, the products are competing with reactants for the respective active sites.
Means products (NADH and acetyl-coA) can drive the reactions backwards. (Can drive E2 and E3 backwards respectively)
Ratios
Have a ratio of [NADH] to [NAD+]
and a ratio of [acetyl-coA] to [coA]. These ratios, if high, have more products than reactants.
Means the lipoyl arm COULD end up with two acetyl-coA’s, if hasn’t been able to offload one of them but can add a second one.
If arm is aceylated at both spots, cannot take hydroxyethyl group from E1-TPP and add it if there is someting in the way.
If cant accept hydroxyethyl group on E2 arm, which becomes acetyl-coA , then cant decarboxylate anymore. If cant decarboxylate anymore, then stop this rxn.
This will cause a backup of things if cant add hydroxyethyl group to arm.
This is substrate lvl inhibition (product)
PDH kinase
PDK, will inactivate by adding phosphate groups.
PDK is directly activated when it interacts with acetylated E2.
E2 stayed acetylated by products inhibiting… products inhibiting means E2 arm cannot become deacetylated by transferring it to a CoA because you have acetyl-coA there instead.
When this arm is acetylated, PDK becomes ACTIVE, will phosphorylate the 3 serines and covalently modify these spots by turning down the activity by making a population of E1 inactive.
If E1 inactive pop is high, overall activity is low which means not taking pyruvate to make Acetyl-coA anymore…..
So, PDHC products INDIRECTLY activate PDK because need to keep arm acetylated, which affects PDK.
PDH phosphatase
PDP, will activate by removing phosphate groups.
Where are these phosphates being added/removed by PDK and PDP
E1 ALPHA subunit which contains up to 3 serines.
PDK and PDP will bind to E1…
If E1 is phosphorylated, the effect of which inhibition types are active?
- BOTH
- substrate level control
- covalent modification
COMBINED inhibitory effect…
Fatty Acid B-oxidation
produced acetyl-coA and NADH.
If these two products inhibit PDHC, will end up saving carb stores when we can use lipid.
Important bc: we have a lot of glucose used for brain during resting conditions, heart normally using FA at rest, when we quickly need to do something, we may use glucose for a bit, but dont really want the heart to do this!
(protect energy store when using another one)
What does insulin do for PDP?
Will ACTIVATE PDP
Means glucose including the glucose in liver can be used to make acetyl-coA
So, we are using up our glucose supplies under these conditions. Whether it is glucose form blodo after meal or needing to use glucose that was stored as glycogen because BS lvls are low.
effectors of PDK
Regulating PDK.
If effectors are not a PDHC product, they are acting on PDK differently.
AcetylCoA and NADH are products, so they will be acting INDIRECTLY on PDK.
Other products will act on PDK directly.
How does pyruvate, ATP and ADP regulate and why (IM CONFUSED HERE, MAKE SURE THESE ARE RIGHT?)
ATP = activating PDK, enough of me, dont want kinase to be active, bc dont want to phos my E1 to make E1 inactive, because then I cant use the PDHC complex
ADP = inactivating PDK becaue we dont want to use this process, want to get energy another way
If PDK is active, will inactivate E1, so need ADP to inactive kinase so wont add phosphate on there????
Pyruvate: same rsn as ADP, wants to inhibit kinase so that you wont phosphorylate the E1
PDP effectors
Ca2+ will activate PDP (enhance its activity) because Ca2+ signals energy need. (muscles are moving, ca release… in liver connected to glycogenolysis)
Mg2+ binds tigher to ATP than ADP, which allows Mg2+ to act as an ATP sensor. Low concentration ATP, excess Mg2+ to activate PDP
