Weilbaecher RS 1- Regulation of Metabolsim Flashcards
What enzyme converts UDP glucose to glycogen? What is it constitutively inhibited by
Glycogen synthase.
Inhibited by GSK-3 phosphorylation
In the liver, how will insulin drive glycogen synthesis?
Insulin stops the constitutive inhibition of glycogen synthase by using PKb/Akt to phosphorylate GSK-3.
It will also activate protein phosphatase-1, which will dephosphorylate 3 enzymes
- Glycogen synthase (activating it)
- Phosphorylase kinase
- Glycogen phosphorylase
How will glucagon and epinephrine drive glycogenolysis?
By activating the Gs subunit, they will lead to the production of cAMP, which activates PKA.
PKA will phosphorylate PP-1, stopping it from affecting it’s 3 target enzymes
Glycogen Synthase (remains constitutively inhibited)
Phosphorylase Kinase
Glycogen Phosphorylase (are able to mobilize glucose)
What aspects of oxidative phosphorylation regulation are consisted in all tissues?
PFK-1 is inhibited by ATP and citrate
Pyruvate dehydrogenase complex is inhibited by the products of beta oxidation (Acetyl-CoA, NADH, ATP)
How will insulin drive glycolysis in the liver?
Insulin will activate the kinase activity of F26BPase/PFK-2, leading to F26PB.
Insulin will also activate PP-1.
In glycolysis, PP-1 will dephosphorylate and activate pyruvate kinase
It will also dephosphorylate and activate PDH
How will glucagon inhibit glycolysis?
Glucagon will activate the phosphatase activity of F26BPase/PFK-2, breaking down F26BP.
It will also phosphorylate pyruvate kinase
Also, it will drive beta oxidation, whose products will inhibit PDH
Which tissue is not under hormonal regulation?
Skeletal
What is unique about pyruvate kinase in skeletal muscle?
It has no allosteric or hormonal regulation
What is unique about glycolysis regulation in the heart?
Glycolysis is stimulated by both epinephrine and insulin
What receptor is necessary for fructose uptake in the liver?
GLUT8
How is glucokinase regulated in the liver?
Glucokinase is typically held by a glucokinase regulatory protein (GKRP) in the nucleus. When glucose levels are high enough, glucokinase is freed and enters the cytosol.
Fructose-6-phosphate levels can cause this as well (fructose metabolism)
When glycolysis slows down, glucokinase returns to the nucleus and re-associates with the regulatory protein.
What are 5 gluconeogenesis substrates? How do they feed into gluconeogenesis?
TAGS can be cleaved into FFA’s and glycerol by HSL.
Glycerol can easy become gluconeogenic substrates
Odd chained free fatty acids can become succinyl-CoA, and any TCA cycle intermediate can be used for gluconeogenesis
Lactate and alanine can become pyruvate, which through pyruvate carboxylase and PEPCK eventually becomes a gluconeogenic substrate.
Also, gluconeogenic amino acids
How does gluconeogenesis bypass pyruvate kinase?
Gluconeogenesis would like to simply reverse the action of pyruvate kinase and turn pyruvate into PEP. However, this action is not reversible and must be bypassed.
To do so, pyruvate is carboxylase will convert pyruvate into oxaloacetate, which becomes malate, leaves the mitochondria, becomes oxaloacetate again, and is turned into PEP by PEPCK.
How is PFK-1 bypassed in gluconeogenesis?
The signals that trigger gluconeogenesis (epinephrine, glucagon) will activate PKA, which activate the phosphatase activity of F26BPase/PFK-2, leading to the breakdown of F26BPase
How is glucokinase bypassed in gluconeogenesis?
Glucose-6-Phosphatase reverses its actions
