Gluconeogenesis Flashcards
What are some sources of glucose?
- Pyruvate
- Lactate
- Amino acids
- Propionate (odd chain fats)
- Glycerol (fats)
Provide examples of substances pyruvate can be converted to?
- Alanine
- Acetyl CoA
- Lactate
- Gluconeogenesis
What is the Cori cycle?
When Lactate is converted to glucose in the liver
What enzyme turns pyruvate to gluconeogenesis?
Pyruvate carboxylase
Does Gluconeogenesis consume or generate ATP?
Consume
What substance does Pyruvate carboxylase require to become active?
Acetyl-CoA
What does pyruvate need t be converted to to get Phosphoenolpyruvate?
- Made into Oxaloacetate (OAA) then Phosphoenolpyruvate (PEP) as PEP -> Pyruvate is an irreversible step
What enzyme converts Pyruvate to oxaloacetate?
Pyruvate carboxylase
- Requires biotin as a cofactor
- ATP and CO2 also required
What enzyme converts Oxaloacetate to Phosphoenolpyruvate?
PEP carboxykinase
- + GTP
WHere does the first step of gluconeogenesis occur (Pyruvate -> Oxaloacetate)?
Mitochondria
majority occurs in cytosol
How is oxaloacetate transfered to the cytosol?
Malate shuttle
What enzymes is biotin a cofactor for?
Carboxylation enzymes
- All add 1-carbon group via CO2
- Pyruvate carboxylase
- Acetyl-CoA carboxylase
- Propionyl-CoA carboxylase
Consumption of what can cause a biotin deficiency (rare)?
Raw egg whites (avidin)
What are symptoms of biotin deficiency?
- Dermatitis
- Glossitis
- Loss of appetite
- Nausea
What does pyruvate carboxyase present with? What are the symptoms?
- Presents in infancy w. failure to thrive
- Elevated pyruvate -> Lactate
- Lactic acidosis
- High alanine also
- V. rare
What enzyme converts F-1,6-BP to F-6-P?
Fructose 1,6 bisphosphatase 1 (rate limiting step)
PFK1 does reverse reaction
What enzyme will high levels of ATP stimulate?
Fructose 1,6 bisphosphatase 1
- Rate-limiting step of gluconeogenesis
What do high and low levels of Fructose 2,6 Bisphosphate cause?
- High = Glycolysis (PFK1)
- Low = Gluconeogenesis (Fructose 1,6 Bisphosphatase 1)
What enzyme catalyses the conversion of F6P to F26BP?
PFK2
What enzyme catalyses the reaction of F26BP to F6P?
Fructose-1,6-bisphosphatase 2
What substances favour glycolysis (PFK1 activity)?
- AMP
- Fructose 2,6 Bisphosphate
What substances decreases glycolysis (PFK1 activity)?
- ATP
- Citrate
What substances decrease gluconeogenesis (Fructose 1,6 Bisphosphatase activity)?
- AMP
- F 2,6 Bisphosphate
What substances increase gluconeogenesis (Fructose 1,6 Bisphosphatase activity)?
ATP
Where does conversion of G6P to Glucose occur?
Mainly in liver and kidneys
- Other organs shunt G6P -> Glycogen
What enzyme converts G6P to Glucose?
Glucose-6 Phosphatase
What molecule can be converted straight to glycogen (bypassing glucose)?
In certain tissues G6P can be shunted to glycogen
Where does the reaction of G6P to Glucose occur in the cell?
Endoplasmic reticulum
Where in the gluconeogenesis/glycolysis pathway does glucagon exert its effects?
- Phosphoenol pyruvate -> pyruvate (slows down this reaction, less pyruvate made)
- Induces F16BP -> F6P (through decreasing F2,6BP),
- Induces G6P -> Glucose (more glucose produced)
What kind of fatty acids can be converted to glucose?
Odd chain fatty acids
How are odd chain fatty acids converted to glucose?
Propionyl coA
- > OAA
- > PEP
- > Glyceraldehyde-3-phosphate
- > F1,6, BP
- > Glucose
How is glycerol converted to glucose?
Glycerol
- > Dihyfroxyacetone phosphate
- > F-1,6-BP
- > Glucose
WHat other hormones (outside glucagon and insulin) may affect glucose levels?
- Epinephrine (raises blood glucose, gluconeogenesis and glycogen breakdown)]
- Cortisol (increases gluconeogenesis enzymes)
- Thyroid Hormone (increases gluconeogenesis)