Trauma and Gluconeogenesis Flashcards
Where does gluconeogenesis occur?
Predominantly in the liver
Also occurs in kidney
What activates and inhibits gluconeogenesis?
Activated by glucagon
Inhibited by insulin
When is gluconeogenesis very active?
Very active following trauma
Very active in Type 2 diabetes and is dysregulated (unopposed glucagon effect because of insulin resistance)
Name the key precursors for gluconeogenesis.
Lactate - from muscle glycolysis, from anaerobic metabolism
Glycerol - from lipolysis of TAG in adipose tissue
Alanine - from proteins
Aerobic vs anaerobic metabolism.
Aerobic - long duration of exercise, occurs in presence of oxygen
Anaerobic - quick bursts of intense exercise, no oxygen
Name the two irreversible steps which are needed to overcome when converting pyruvate back to glucose (in gluconeogenesis).
Pyruvate to phosphoenolpyruvate (PEP)
F1,6bisP to F6P
List the 5 key enzymes which are important in bypassing the enzymic roadblocks in GNG.
Glucoses-6-phosphatase Fructose-bi-phosphatase Pyruvate carboxylase (PC) PEP carboxykinase (PEPCK) Pyruvate dehydrogenase (PDH)
What is Beta Oxidation?
Fatty acids into acetyl CoA
What is ketogenesis?
Acetyl CoA into ketone bodies
What is CAC?
Acetyl CoA into CO2, ATP, NADH, FADH2
Describe how we convert pyruvate into phosphoenolypyruvate (PEP).
Accumulation of acetyl CoA from glycolysis and beta oxidation
This inhibits pyruvate dehydrogenase (PDH) - which would normally convert pyruvate into acetyl CoA
Instead PC is activated, transferring pyruvate into oxaloacetate
Oxaloacetate is converted into PEP via PEPCK
Fasting stimulates gluconeogenesis
What effect does glucagon have on the enzymes involved in Pyruvate –> PEP.
Glucagon wants to increase glucose - thereby stimulate gluconeogenesis
Promotes phosphorylation of PK - inhibits PK
Activates PEPCK
What effect does insulin have on the pathway: pyruvate –> PEP.
Insulin wants to decrease glucose - thereby promote glycolysis.
- Activates PK (promotes dephosphorylation of PK)
- Inhibit PEPCK
List things that inhibit PEPCK. (converts oxaloacetate to PEP) (stimulate gluconeogenesis)
Insulin
Metformin
Thiazolidinediones
List substances the activate PEPCK (oxaloacetate to PEP)
Cortisol
Thyroid hormone
Glucagon
Adrenaline