Metabolic Fate of Pyruvate Flashcards
What is the structure of pyruvate
- ketone
- carboxyl group
- 3 carbon structure
What are some of the metabolic fates of pyruvate
- CAC, acetyl CoA
- Produce lactate
- Produce alanine
- F.A’s
- Oxaloacetate
How is pyruvate converted into lactate
pyruvate is going to be reduced by NADH to produce lactate and NAD+
- reversible step
- Lacate dehydrogenase
When is lactate produce
- when there is low oxygen is in the muscle
Can lactate be used a fuel in the muscle? Why or why not?
Yes, but it needs O2 to be used by muscle. If O2 is not present then NO
What is the overall reaction for glucose degradation to lactate
Glucose + 2 ADP + 2 Pi <–> 2 Lactate + 2 H2O + 2 H+
why is pH decrease in the muscle during the production of lactate
- The overall conversion of glucose to lactate produces not only lactate itself but H+ ions. Those ion decrease the pH of the muscle producing what would be called Lactic acid
Explain the Bohr effect
- the pH of blood decreases
- protonation of histidines
- Binding of 2,3-BPG
- Decrease affinity for HbO
- Offloading of O2 to muscle
- Stabilizing the DexoyHB formation
Explain the cori cycle
**In the muscle - Anaerobic **
- glucose is converted into lactate via glycolysis ( NADH + H+ –> NAD+ and ADP + Pi –> ATP)
- OR glycogen is converted into lactate (via glycogenolysis, NADH + H+ –> NAD+ and ADP + Pi –> ATP)
- Lactate is sent to the liver through the blood
**In the liver Aerobic **
- Lactate is converted back into glucose (via gluconeogenesis, ATP + GTP + NAD+ –> ADP + Pi + GDP)
Lactate product can also be sent to the heart to produce ATP
Under what conditions can pyruvate be converted to Acetyl CoA?
aerobic conditions, in the cell membrane
Name the different transport mechanism from glucose all the way to Acetyl CoA
-Glucose transported into cytosol via GLUT transporters
- Once glucose is converted to pyruvate, then pyruvate goes across a porin which is on the outside of the mitochanrial membrane
- Then pyruvate translocase transports (know as a H+ linked monocarboxlyate transporter) pyruvate across mitchandrial memebrane with an H+
- Into the mitochandrial matrix for conversion to A. CoA
What is a transactylation
Transfer of an acetate to CoA (formation of a high energy molecule)
What are the general 3 major steps that occur in the PDC
- decarboxylation
- Oxidation
- Transcetylation
What are the cosubstrates in the PDC? And why are they considered co substrate
- CoA - SH
- NAD+
They bind to enzyme with substrates and leave enzyme at the end of the reaction
What are the prostetic groups in the PDC and why are they considered prostetic groups?
- TPP
- Lipoate
- FAD
- Tightly bond specific nonpolypeptide unit
What are the 3 enzymes of the PDC?
E1: TPP
E2: Lipoate
E3: FAD
COME BACK TO SLIDE 18
List the steps the occur in the pyruvate dehydrogenase complex
- Pyruvate is decarboxylated (removal of CO2) and TPP cofactor binds to hydroxyethyl of E1 –> RLS
- Hydroxyethyl group is transferred to lipoamide disulfide. E1 catalyzes reaction where hydroxyl group is oxidized to actyl group and disulfide bonds are reduced (energy conserved in thioester linkage)
- E2 catalyzes a transesterification reaction, where there is a transfer of acetyl group to CoA. A-CoA is formed and dihydrolipoamide is formed
- Reduced Lipoamide is re-oxidized by reactice cyclic disulfide group, this group is regenerated by FAD
- NAD+ is oxized by FADH2, making NADH
What is the reaction for pyruvate to Acetyl CoA
Pyruvate + NAD+ +CoA –> A. CoA + NADH + CO2
What is the rate limiting Step in the PDC
the 1st step
What activates pyruvate dehydrogenase kinase
Acetyl CoA + NADH
what deactivate pyreuvate dehydrogenase kinase
- ADP
- NAD+
- HS- CoA
- Pyruvate
What activates pyruvate dehydrogenase phosphotase
- Ca2+ in muscles –> increased ATP use
- Insulin
- Turns on by dephosphorlating E1
What is the active form an inactive form of E1
Active form - has the OH group attached
Inactive form - P attached
what can inhibit E2
Acetyl CoA BUT phosphorylation is more important
What can inhibit E3
NADH BUT phosphorylation is more important