Gluconeogenesis Flashcards
gluconeogenesis definition
a metabolic pathway that results in the synthesis of glucose from certain non carbohydrate substrates
what are the main substrates for gluconeogenesis?
lactate, glycerol and amino acids such as alanine and glutamine
what does gluconeogenesis take place?
primarily in the liver and partially in the kidney cortex
pathway involves a mitochondrial section and cytosolic section
daily glucose requirements by different organs
brain 110g
muscle- 30g
renal medulla- 30g
erythrocytes- 25g
which organs can’t use fatty acids + why?
brain, renal medulla and red blood cells
fatty acids bound to albumin cannot pass the blood-brain barrier
breaking down fatty acids requires a lot of ATP, and thus more oxygen and thus more superoxides and oxidative stress
how long would our fasting stores last?
12 hours
differences between glycolysis and gluconeogenesis
some enzymes in glycolysis are irreversible, so need different enzymes
energy input for gluconeogenesis exceeds reversed glycolysis, 6 ATP vs 2
different control mechanisms
involves mitochondria, not just the cytosol
stages of mitochondrial part of gluconeogenesis
- pyruvate to oxaloacetate, catalysed by pyruvate carboxylase, using ATP
- oxaloacetate reduced to malate using NADH and catalysed by malate dehydrogenase
- malate diffuses across mitochondrial inner membrane
- malate oxidised to oxaloacetate, forming NADH and catalysed by malate dehydrogenase
- phosphoenolpyruvate carboxykinase catalyses oxaloacetate to phosphoenolpyruvate using GTP
why does this long-winded mitochondrial pathway need to take place?
in glycolysis phosphoenolpyruvate to pyruvate is catalysed by pyruvate kinase in an irreversible reaction, so cannot just back track
oxaloacetate cannot diffuse through membrane, so malate has to be formed
stages of cytosolic part of pathway
- phosphoenolpyruvate to 2-phosphoglycerate catalysed by enolase
- 2 phosphoglycerate to 3 phosphoglycerate catalysed by phosphoglycerate mutase
- 3-phosphoglycerate to 1,3 biphosphoglycerate catalysed by phosphoglycerate kinase using ATP
- 1,3-biphosphoglycerate to glyceraldehyde 3 phosphate catalysed by glyceraldehyde 3 phosphate dehydrogenase using NADH
- glyceraldehyde 3 phosphate to dihydroxyacetone phosphate catalysed by triose phosphate isomerase
- glyceraldehyde 3-phosphate and dihydroxyacetone phosphate to fructose 1,6- diphosphate catalysed by aldolase
- fructose 1,6-bisphosphate to fructose 6 phosphate, catalysed by fructose 1,6-bisphosphatase
- fructose 6 phosphate to glucose 6 phosphate catalysed by phosphoglucose isomerase
stages of SER part of pathway
glucose 6 phosphatase catalyses the conversion of glucose 6 phosphate to glucose
where is glucose 6 phosphatase expressed
only expressed in the kidney and liver
what transporter does the glucose travel through?
GLUT 2 from SER to blood
how many substrates needed + why?
need two pyruvates, double everything up prior to glyceraldehyde 3 phosphate, as this needs to be converted to dihydroxyacetone phosphate and then react with itself
4 ATPs
4 NADH
2 GTP
2 PYRUVATES
how is pyruvate derived during gluconeogenesis?
lactate and alanine supplied to the liver from circulation