Lecture 31 Flashcards
What are the two main checkpoints in TCA (citric acid cycle)?
- pyruvate Dehydrogenase complex
- citrate synthase
What are two other regulated reactions other than the two main checkpoints in the TCA cycle?
- isocitratre dehydrogenase
- a-ketogluterate dehydrogenase complex
What do all the four regulated reactions in the TCA cycle have in common?
- Highly exergonic
- these reactions keep the cycle going (usually) in a clockwise direction
- if the flow of metabolites at these reactions is slowed the whole cycle will slow down
What is associated with the energy rich state of the cell?
High Concentrations of ATP, acetyl-CoA, NADH, succinyl-CoA, and citrate
What is associated with energy poor state of the cell?
- these are your activators because they are substrates or because they work through allosteric effects
- AMP, NAD+, CoA, ADP
What is an allosteric activator at three of the four regulator steps?
Ca2+
What inhibits PHD?
ATP, Acetyl-CoA, NADH, and Fatty Acids
What activates PHD?
AMP, CoA, NAD+, Ca2+
what inhibits citrate synthase?
NADH, succinyl-CoA, citrate, ATP
What activates citrates synthase?
ADP
What inhibits isocitrate dehydrogenase?
ATP
What activates isocitrate dehydrogenase?
Ca2+, ADP
What inhibits a-ketogluterate dehydrogenase complex?
Succinyl-CoA, NADH
What activates a-ketogluterate dehydrogenase complex?
Ca2+
PDH complex covalent modification?
- In mammals but not in smaller eukaryotes or prokaryotes
- phosphorylation of the E1 subunit regulates the activity
- there is kinase and a phosphatase activity that puts on or takes off a phosphate on the E1 subunit
What would put the PDH complex in the active state?
NAD+, CoA, ADP, and pyruvate inhibit the kinase activities the PDH complex tends to the unphosphorylated state-active state
What would put the PDH complex in the inactive State?
NADH, Acetyl-CoA induce the kinase, so the PDH complex becomes more phosphorylated and is inactive
What regulates the activity of the pyruvate dehydrogenase complex subunits E2 and E3
- by the concentrations of NAD+/NADH and HS-CoA/Acetyl-CoA
- NAD+ activates E3
- NADH inhibits E3
- HS-CoA activates E2
- Acetyl-CoA inhibits E2
In the TCA cycle what input channels are there?
Pyruvate a-ketogluterate Fumurate Succinate Aspartate
BUT NOT Oxaloacetate nor acetyl-CoA
In the TCA cycle was output channels are there?
phosphoenolpyruvate
citrate
malate
Aspartate
What is the most likely reason that high amounts of metabolites would enter the TCA cycle?
from catabolism of carbohydrates or fatty acids (ex: from the diet)
anaplerotic reactions
the reactions that replenish the metabolites in the citric acid cycle
What is the main anaplerotic reaction?
replenishment of oxaloacetate
What side of the TCA cycle does the metabolites needed for anabolic reactions come from? What is the consequence of any withdrawel from this?
Right side of the TCA cycle
-decrease in the oxaloacetate concentration
Glyoxylate cycle
in microorganisms and plants
- uses two molecules of acetyl-CoA in each cycle and does not release CO2
- results in efficient biosynthesis of oxaloacetate
- succinate is produced and is transferred to the citric acid cycle
Where does the TCA cycle occur?
eukaryotes-mitochondrial matrix
bacteria-cytosol
What is gained per each cycle of the TCA cycle?
for each acetyl-CoA oxidized by the cycle, the energy gain is three NADH, one FADH2, and one ATP(GTP)
Mitochondrion
has two bilayer membranes
-outer and inner membrane
Phase 1 of catabolism is located where?
Glycolysis-to the point of pyruvate takes place in the cytoplasm
-outside of the outer membrane of the mitochondrion
Outer membrane of mitochondrion
-porous thus is easy equilibration of material from the cytoplasm across the outer membrane into the inter membrane space
Inner membrane of mitochondrion
75% protein by weight
-completely closed and transporters are needed for movement of molecules
Phase 2 of catabolism
citric acid cycle plus fatty acid oxidation and acid degradation
- takes place in the inner membrane of the mitochondria
- reduced electron carriers (NADH and FADH) will accumulate inside the inner membrane
Entry of Pyruvate into the TCA cycle
- called oxidative decarboxylation because CO2 is lost from pyruvate and there is oxidation
- enzyme: pyruvate dehydrogenase complex
Pyruvate dehydrogenase
- enzyme used to covert pyruvate to acetyl-CoA
- contains three types of subunits (E1, E2, and E3)
E1 subunit of pyruvate dehydrogenase complex
pyruvate dehydrogenase
-coenzyme: TDP (aka TPP)
E2 subunit of pyruvate dehydrogenase complex
dihydrolipoamide acetyltransferase
-coenzyme:lipollysine
E3 subunit of pyruvate dehydrogenase complex
dihydrolipoamide dehydrogenase
-coenzyme: FAD
Reaction 1 of TCA cycle
enzyme: Citrate synthase
- Acetyl-CoA is a high energy compound and it is used as a substrate contributor to the large standard free energy decrease making the reaction and irreversible one
Succinate Dehydrogenase
-located in the inner side of the inner mitochondrial membrane
