Glycolysis and the TCA cycle Flashcards
Key regulatory enzymes of glycolysis
Hexokinase , PFK, Pyruvate kinase
Nets of glycoolytic pathway
2 ATP 2 NADH 2 Pyruvate
Explain Km and affinity for GLucokinase
high Km , low affinity for glucose .. only uses glucose when glucose levels are very high
Increase of G6P means a decrease in
glucokinase
Committed step go glycolysis
PFK
Two isoforms of pyruvate kinase
Liver isoform - regulated by phosphorylation Muscle - not reg by phos
Net yields of the TCA
3 NADH 1 GTP 3 H+ 1 FADH2
Key regulation sites at TCA
Citrate synthase Isocitrate dehydrogenase Alpha ketoglutarate dehydrogenase
Things that can be turned into Ace COA
AA FA Pyruvate
Things that can be turned into OAA
AA Pyruvate , Propionyl COA
Things to know about pyruvate dehydrogenase complex
- requires TPP, lipoid acid, and FA 2. Requires 3 subunits E1 E2 E3 3. Catalyzes the oxidative decarboxylation of pyruvate
More efficient shuttle
glycerol phosphate shuttle
PFK influenced primary by
energy charge of cell and nutritional status of the liver
Activators of glucokinase
Inhibitors
Insulin
Inhibitors: G6P
A and I of PFK
A:
AMp,
F2,6-BisP
I:
ATP
Citrate
A and I of Pyruvake kinase
A:
AMP,
F1,6-BisP- (earlier intermediate of that pathwasy that tells the cycle to keep up)
I:
ATp, Ace-CoA, Alanine
Enzymes def in Hemolytic anemia
Pyruvate kinase (95%)
Phophoglucose isomerase (4%)
What feeds into glyc pathway and where ?
GLycerol : at DHAP
GLycogen at G6P
Alanine and lactate at pyruvate
Key regulatory enzymes of the TCA
Citrate synthetase
Isocitrate dehydrogenase
Alpha keto glutarate dehydrogenase
Where is pyruvate dehydrogenase enzyme located ?
Requires what 3 things
Mito matrix
Tpp
Lipoic acid
FAD
Explain CoA, NAD+ , and AMP regarding Pyruvate dehydrogenase complex
All of these activate
“Keep the cycle going and make energy”
Ace-CoA, NADH, GTP/ATP regarding pyruvate dehydrogenase complex
Inhibitors
” slow down , we have enough”
Explain dephosphorylation and phosphorylation of pyruvate dehydrogenase complex
Dephopshorylation =activation
Phosphorylation =deactivation
What effects does pyruvate have on the Pyruvate dehydrogenase complex?
its is the substrate so its activates it
Pyruvate also inhibits the kinase which deactivates the complex, so its like taking the breaks off the car
High NADH/NAD+ and high Ace-CoA/CoA levels will do what to pyruvate dehydrogenase complex?
SLow it down “says, we have enough stuff”
But these ratios also activate a kinase which in turn inhibits the enzyme
What effect does calcium have on the phosphodehydrogenase complex
It activates the phosphotase which activates the complex
Given a High NADH and High Ace-CoA ratios , these do what to the pyruvate dehydrogenase complex?
Inhibit the phosphatase , therefore inactivating the complex
What inhibits citrate synthase ?
ATP, NADH, and Succinyl Co-A
Isocitrate dehydrogenase is inhibited by and activated by?
I: ATP, NADH
A: ADP, Calcium
Alpha keto glutarate is activated and inhibited by ?
I: ATP, NADH, Succininyl CO-A
A: AMP , Calcium
In oxidative phosphorylation, the protons are pumped into
intramenbranous space
Complexes that pump hydrogen out
1, 3, 4
1 and 3 pump out 4H+
and 4 pumps out 2H+
Role of ubiquinone
What enzyme is associated with complex 2
Succinate dehydrogenase
Oxidizes cytochrome C
Complex 4
Explain the cost of ATP synthesis
the matrix has a -4 charg (ATP)and cytosol has a -3 charge (ADP) before ATP goes to cytosol
Once ATP is exchanged to cytolsol, charge goes from -3 to -4 ,so inessence that costs 1 proton
ATP to NADH and FADH2 ratio
1NADH=2.5 ATP
1FADH2= 1.5 ATP
Gives overview of regulating oxidative phosphorylation
muscle uses ATP
increase in ADP
increase in ATP synthesis
decrease in proton gradient
increase ETC to restore gradient
decrease in NADH/NAD+ and FADH2/FAD ratios
increase fuel oxidation
Inhibitors of complexes
complex 1: rotenone , Amytal, Demerol,
Cyt C- Carbon monoxide , cyanide , azide,
ATP synthase - oligomyocin
Membrane- uncouplers , 2,4-dinitrophenol, dicumarol, FCCP
