Week 9 Flashcards
where does glycolysis happen? is it catabolic or anabolic?
cytoplasm, catabolic
what are the products of glycolysis?
2 ATP (4-2), 2 NADH, 2 pyruvate
what is the first step of glycolysis? why is it spontaneous? why is this step important? how is this step regulated?
hexokinase (glucokinase): glucose C6 phosphorylated with ATP forming more stable ADP
glucose transporters can’t transport G6P out of cell… trapped
regulated by: G6P (product) inhibits glucokinase (enzyme)
what is the third step of glycolysis? why is it spontaneous? how is it regulated?
phosphofructokinase 1 (PFK-1): C1hydroxyl phosphorylation with ATP forming more stable ADP
inhibited by: citrate and ATP (substrate but PFK-1 has second allosteric inhibitory ATP binding site)
activated by: AMP/ADP and F-2,6-BP (side reaction with PFK-2 if F6P builds up… feed forward regulation)
what is the last step of glycolysis? why is it spontaneous? how is it regulated?
pyruvate kinase: transferase of phosphate from PEP (very unstable) onto ADP making ATP and pyruvate
2 types of regulation:
allosteric:
activated - AMP, F-1,6-BP (feed forward)
inhibit - ATP, intermediate metabolites (alanine, acetyl-CoA) feedback inhibition
covalently regulated by phosphorylation:
phosphorylated = active
dephosphorylated = inactive
under what conditions is PK phosphorylated and dephosphorylated? what enzymes do this?
phosphorylated - low blood glucose, glucagon signals through GPCR to save energy and slow down glycolysis by phosphorylating PK by Protein Kinase A
dephosphorylated - blood glucose levels restored, insulin signals for glucose uptake and phosphatase action dephosphorylates PK
how does glycogen phosphorylase carry out glycogenolysis? how is it regulated? what molecule comes out?
phosphate attacks reactive anomeric C1
inhibited: ATP and G6P
stimulated: AMP
G1P
what does phosphoglucomutase do and why is it needed to carry out glycolysis?
G1P must first be converted to G6P to enter glycolysis
G1P phosphorylated by phosphorylated serine residue in phosphoglucomutase to G-1,6-BP. phosphate from C1 then goes back onto serine residue
what are the 4 steps in glycogen synthesis?
- hexokinase: glucose -> G6P
- phosphoglucomutase: G6P -> G1P
- UDP-glucose pyrophosphorylase: G1P -> UDP-glucose (activated G1P)
- glycogen synthase: makes a-1,4-glycosidic bond on noon-reducing end
what are the 3 prosthetic groups and 2 co-subrstrates in the PDC?
prosthetic groups: thiamine pyrophosphate (TPP), lipoamide, and FAD
co-substrates: CoA and NAD+
what is the net reaction of the PDC? (1 round)
pyruvate + CoA-SH + NAD+ —> acetyl CoA + CO2 + NADH (mito)
why is the PDC favourable?
release of CO2 increases entropy
explain the redox of the PDC
reduction: NAD+ to NADH
oxidation: pyruvate to acetyl CoA
what is each enzyme of the PDC subunits and what do they do?
E1: pyruvate dehydrogenase - decarboxylation
E2: dihydrolipoyl transacetylase - makes and releases acetyl CoA
E3: reduces NAD+ to NADH and returns enzyme to original state
how is each subunit in the PDC regulated? compare their states when muscles are at rest vs when running. explain the role of Ca2+ in this process
E1: covalent modification by phosphorylation (kinase vs phosphatase)
E2: acetyl CoA
E3: NADH
rest: NADH and acetyl CoA activating PD kinase and inactivating E2 and E3
running: pyruvate and ADP inhibit PD kinase, Ca2+ activates PD phosphatase
