Gluconeogensis Flashcards
when does Gluconeogenesis occur
- occurs in the liver under starvation
- occurs in periods of intense anaerobic exercise
what is Gluconeogenesis
this is making glucose
what are the substrates that can be used in glucokneosis
- Using carbon part of amino acids from proteins
- From lactate in the blood coming from glycolysis in the muscle tissue from anaerobic respiration
- From glycerol
what cannot undergo glucogenogensis
Can’t be done from fatty acids as they produce acetyl CoA which can’t be used to make glucose, but can provide energy for the reaction.
what are the 3 steps that have to be reversed in glycolysis in order for gluconeogensis to happen
- glucose being converted to glucose-6-phosphate via glucokinase (only in the liver)
- o Fructose-6-phosphate converted to fructose-1,6-bisphophate using phosphofructokinase
- phosphoenolpyruvate to pyruvate via pyruvate kinase
how does the liver overcome the 3 unidirectional steps
o Glucokinase can be overcome using glucose-6-phosphatase, therefore glucose-6-phosphate can be converted back to glucose
o Phosphofructokinase is overcome by fructose-1,6-bisphosphatase, therefore fructose-1,6-bisphophate is converted back to fructose-6-phosphate
o Pyruvate kinase is overcome by pyruvate carboxylase (PC), malate dehydrogenase (MDH) and phosphoenolpyruvate carboxykinase (PEPCK) this causes pyruvate to be converted back to phosphoenolpyruvate
describe how pyruvate is converted back to PEP (phosphoenolpyruvate)
o Pyruvate passes into mitochondria and then converted to oxaloacetate by pyruvate carboxylase
- pyruvate is converted form a 3 carbon molecule to a 4 carbon molecule
- energy is required for this reaction it converts ATP to ADP
o No transporter for oxaloacetate so converted to malate to pass out of the mitochondria this is catalysed by MDH
o Malate then converted back to oxaloacetate in the cytosol this is catalysed by MDH again
o PEPCK converts oxaloacetate phosphoenolpyruvate
- 4 carbon compound converted to a 3 carbon compound this produces carbon dioxide and GTP is converted to GDP as this requires energy
o Called a malate shuttle as malate used to get between the mitochondria matrix and cytosol
- phosphoenolpyruvate can then go up the glycolysis route from pyruvate to glucose and makes glucose
describe fatty acid metabolism
- fatty acids are broken down to acetyl CoA and NADH by beta oxidation
- acetyl CoA cannot be converted to glucose
- Acetyl CoA activates pyruvate carboxylase and this inhibits pyruvate dehydrogenase
- This means that any compound that can produce pyruvate will not form acetyl CoA and instead be used to glucose formation using the energy from fatty acid oxidation
- energy for fatty acid oxidation
what does the cori cycle allow for
• The Cori cycle allows for anaerobic metabolism to take place in muscles.
describe how the cori cycle works
• Liver turns lactate into pyruvate using lactate dehydrogenase to remove it from the system and then pyruvate into glucose.
why does muscle run on fatty acids even during aerobic exercise
• Muscle can run on fatty acids even during aerobic exercise so there is enough glucose for the brain and other organs that have a large energy requirement
describe how glucose is produced from glycerol
- Glycerol produced from the breakdown of triglycerides (= triacylglycerols) stored in adipose tissue
- Enters as DHAP (dihydroxyacetone phosphate) in the middle of glycolysis/gluconeogenesis
describe how glucose can be produced from glycogenic amino acids
• Glucogenic amino acids can be broken down into pyruvate or oxaloacetate to then make glucose, all except for ketogenic Aa = leucine and lysine. .
How can the kidney perform gluconeogensis
- it uses glutamine
How do you control gluconeogensis
- control using glucagon, adrenaline and insulin
what happens in diabetes and how do you treat it
- In diabetes there is an increased supply of precursors (glycerol, amino acids) along with increased fatty acids as well as a high glucagon to insulin ratio
- Treated by reducing hepatic gluconeogenesis
all amino acids are…
glycogenic amino acids except leucine and lysine
if an amino acid can be ..
broken down to produce pyruvate or oxaloacetate then glucose can be synthesised from the amino acid
what does insulin do to gluconeogenisis
insulin inhibits gluconeogenisis
what activates gluconeogenisis
- Glucagon and adrenaline activate it and by cortisol also activates it in the liver
how does insulin inactive gluconeogensis
- Insulin breaks down cAMP and turns off kinases and turns on phosphorylases and turns on all the enzymes and inactivates glyconeogensis
how is gluconeogensis switched on and off
phosphorylate and dephospho rylation
how does glucagon activate gluconeogensis
- increases cAMP
- increases protein kinase A
- increases pyruvate dehydrogenase
how is pyruvate dehydrogenase allosterically controlled
- controlled by acetyl CoA and NADH levels , if these levels are high then it is inactivated
- this is in a edition to the action of the kiasne and phosphate controlled by hormones
what activates pyruvate carboxylase
acetyl-CoA
what are the main glycogenic amino acids
alanine and glutamine
where does glycerol enter the gluconeogensis cycle
- glycerol is from TAG breakdown
- it enters as dihydroxyacetone phosphate in the middle of glycolysis/gluconeognesis
what needs to happen for the cori cycle to work
- in muscle the conversion of pyruvate to Acetyl CoA must be blocked - this is done by oxidation of fatty acids creating more Acetyl CoA
- The TCA cycle can also be inhibited by anaerobic conditions
