Gluconeogenesis Flashcards
When do we need gluconeogenesis?
In exercise- when lactate is produced this can be converted to glucose
- Short term fasting- intermediates of carb synthesis (oxaloacetate / pyruvate) –> aa e.g. alanine (aa)–> glucose
- Diabetes- ironically gluconeogenic pathway turned on although blood glucose levels in blood are high not detected by liver cells believe insufficient glucose in cell
Leads to more glucose pumped into blood–>exacerbate hypoglycaemia as cells not taking glucose up
- Trauma- insulin receptors don’t get to surface as well as they should- hence gluconeogenesis stimulated
How much glucose is required?
• Glycogen levels run out 12 hrs after ingestion
• After this there is an increase in the gluconeogenic pathway
• This will last a few days
• In starvation conditions (where haven’t eaten for a few days) we still have some gluconeogenesis but also switch to fat metabolism
And we have ketone body formation
- enough glycogen stores to last about 1 day
What cells prefer glucose as substrate
- Brain and RBC (as no mitochondria so no oxidative phosphorylation- need glucose for glycolysis)
What molecules go through gluconeogenic pathway?
- Lactate (–> glucose)
- aa e.g. alanine
- Triglycerides form adipose tissue break down (glycerol–> gluconeogenic pathway and free fatty acids- B-oxidation pathway)
Which tissues undergo gluconeogenesis?
- Liver (main tissue)
- Kidney
- Small intestine
Where does this take place and why?
- cytosol- as most enzymes same as those for glycolysis
Explain pathway
- Reversal of glycolysis
- Except for 3 steps:
Pyruvate–> PEP
Fructose 1,6 bisphosphate–> F6P
G6P–> Glucose
Explain in further detail 1st step that differs to glycolysis in gluconeogenic pathway
- pyruvate–> PEP (2-phosphoenolpyruvate) in the MITOCHONDRIA-
pyruvate +CO2 +ATP–> oxaloacetate + ADP + Pi - via pyruvate carboxylase (mito.)
- requires CO2 and cofactor biotin (B6)
- oxaloacetate converted to malate
oxaloacetate+ NADH + H+–> NAD+ + malate (malate shuffle) - Malate passes out of nitochondria
- once in cytosol using NAD+ back to oxaloacetate
- oxaloacetate + GTP–> PEP + GDP +CO2 via PEP carboxylase
- super mouse if PEP in XS
Why is pyruvate carboxylase useful?
- Found in all tissues
- antipleuritic reaction (restoring intermediates- in this case of the TCA cycle)
- Forms oxaloacetate from pyruvate
- oxaloacetate needed to form a-ketoglutarate, isocitrate etc
Explain in further detail 2nd step that differs to glycolysis in gluconeogenic pathway
fructose 1,6 BP to fructose 6 phosphate via fructose 1,6- diphosphatase
- reciprocal regulation with glycolysis enzyme phosphofructokinase
- fructose 1,6-biphosphate +H2O–> fructose 6-phosphate +Pi
(imagine P group being replaced by OH)
Explain in further detail 3rd step that differs to glycolysis in gluconeogenic pathway
- G6P + H2O–> glucose +Pi
imagine P being replaced by OH
Overall reaction
2 pyruvate +4ATP +2GTP +2NADH +6H2O–> glucose +4ADP +2GDP+ 8Pi +2NAD +2H+
Outline how glycolysis and gluconeogenesis is controlled
- allosteric effectors
- hormonal regulators
What are allosteric regulators of glycolysis/ glycogenolysis
Glycolysis- phosphofructokinase: activated by F2,6-BP, AMP
Inhibited by citrate, H+ and ATP
Gluconeogenesis: instead inhibited by AMP, F2,6- BP
activated by citrate
Also inhibition/ activation going from pyruvate to phosphoenolpyruvate
Hormonal regulation of gluconeogenesis/ glycolysis
- Insulin- promotes synthesis of glycolytic enzymes (phosphofructokinase- fructose-6P–> fructose 1,6-BP)
Also inhibit synthesis of PEPCK- phosphoenolpyruvate carboxylase (oxaloacetate–> phosphoenolpyruvate) REM pyruvate–> oxaloacetate via pyruvate carboxylase - Glucagon- increases expression PEPCK and F1,6BPase
