Glycolysis +gluconeogenesis regulation
What is PEPCK?
isocitrate to alpha KG
alpha Kg to succinyl coa
malate to OAA
succinate to fumarate
which complex does not pump protons into the membrane
complex 2
where does the gluconeogenesis step occus in the calvin cycle?
stage 2
what is required to begin glycogen synthesis?
glycogenin
If F 2,6 BP concentration is high, what happens to glycolysis + gluconeogenesis?
Glycolysis on
Gluconegenesis off
Describe the cofactors used for each subunit of PDH
E1 - TPP
E2 - Lipamide
E3 - FAD
name the 4 complexes of ETC
NADH-Q oxidoreductase
Succinate Q reductase
Q cytochrome c oxidoreductase
Cytochrome C oxidase
describe the fixation step of the calvin cycle
co2 is fixed by combining with ribulose 1,5 bisphospahte to form two molecules of 3PG
three fates of G6P
Glycolysis
Free glucose for release in bloodstream
PPP for NADPH or ribose derivatives
Describe formation of OAA, including enzymes and location.
pyruvate taken to mitochondrial matrix and converted to OAA
reduced to malate by malate DH
malate taken to cytosol where it is oxidized back to OAA by cytoplasmic NAD+ linked malate DH
How much ATP is produced per turn on the CAC? Describe how many ATP are produced by NADH, FADH2 and where the extra one comes from
10 ATP total
2.5 per nadh
1.5 per fadh2
1 atp from atp used during succinyl coa to succinate
describe the structure of atp synthase
F0 (rotor) component: embedded in the inner mito membrane and contains the proton channel
F1(stator) component: protrudes into the mito matrix and contains the catalytic activity
how does TK and TA stabilize carbanionic intermediates?
TK uses a TPP prosthetic group
TA uses a Lys residue
explain how the debranching enzyme works?
Transferase and alpha 1,6 glucosidase remodel glycogen
Transferease shifts a block of three glucosyl residues from the outer branch to the main chain
Alpha 1,6 glucosidase (debranching enzyme) hydrolyses the remaining 1,6 glycosidic bond
Describe the different forms of hexokinase and pyruvate kinase
hexokinase-
in the liver it exists as glucokinase
not inhibited by G6P and phosphorylates glucose only when it is abundant
pyruvate kinase-
L type in liver (regulated by reversible phosphorylation)
M type in muscle
Predict the effect of a mutation that enhances the activity of the kinase associated with the PDH complex
Enhanced kinase activity will result in a decrease in the activity of the PDH complex because phosphorylation by the kinase inhibits the complex.
The most common metabolic sign of mitochondrial disorders is lactic acidosis. Why?
the only means of generating ATP is by anaerobic glycolysis, which will lead to an accumulation of lactic acid in blood.
describe mode 2 of PPP (both R5P and NADPH)
G6P converted to 1 molecules of Ri5P and generates 2 NADPH
Ribulose then isomerized to R5P
G6P + 2NADP+ + H2O → R5P + 2NADPH + 2H+ + CO2
explain the process of glycogen synthesis
UDP glucose created
glycogenin primer is created
Branching enzyme creates branches by cleaving alpha 1,4 linkages
Transfers a 7 residue block and reattaches it with a alpha 1,6 linkage
New branch must be at least 4 residues from existing branches
Balanced reaction for gluconeogenesis
2Pyruvate+4ATP+2GTP+2NADH+6H2O→Glucose+4ADP+2GDP+6Pi+2NAD++2H+
Malonate is a competitive inhibitor of succinate dehydrogenase. How will the concentrations of CAC intermediates change immediately after the addition of malonate?
Succinate will increase in concentration, followed by alpha KG and the other intermediates “upstream” of the site of inhibition.
describe how complex 1 works
Q accepts 2 electrons from NADH, generating Q2-
The negative charge causes a conformational change and protons enter the intermembrane space
Flow of two electrons from NADH to CoQ through NADH Q oxidoreductase leads to the pumping of 4 H ions out of the matrix
Q2- takes up two protons from the matrix and is reduced to QH2, then leaving Complex 1
Describe Mode 3 (nadph needed and not R5P)
G6P is oxidized to Ri5P producing two NADPH and 1 CO2
Ri5P converted to R5P
R5P can make F6P and G3P in the non-oxidative phase and convert this back to G6P using gluconeogenesis
explain one way in which glycogen synthase is regulated? (insulin, glucagon/epinephrine/PP1)
Protein Phosphatase 1 dephosphorylates proteins to decrease the rate of glycogen breakdown
Inactivates phosphorylase a and phosphorylase kinase
Converts glycogen synthase b to glycogen synthase a
PKA phosphorylates phosphorylase kinase and inhibits glycogen synthesis
Insulin inactivates glycogen synthase kinase through Tyr kinase signal transduction pathway and stimulate glycogen synthesis