lecture 22 - feeding sugars into glycolysis Flashcards
How is glucose synthesised?
Glucose can be synthesised from non-carbohydrate precursors by gluconeogenesis, usually common substrate, pyruvate
Equilibrium steps are shared with glycolysis. The direction of the reaction is set by the relative levels of substrates and products
How is pyruvate converted to PEP?
- Pyruvate + ATP + HCO3- –> oxaloacetate + ADP =Pi (pyruvate carboxylase)
- oxaloacetate + GTP –> PEP + GDP + CO2 (PEP carboxykinase) (the reverse reaction of the first two steps is catalysed by pyruvate kinase)
Pyruvate to PEP is highly endergonic, and therefore requires two steps, each using one ATP/GTP.
The intermediate oxaloacetate has a high energy content, allowing synthesis of PEP.
IRREVERSIBLE STEPS
What are the other irreversible steps?
- F1.6-BP + H2O –> F6-P + Pi (fructose 1.6-bisphosphatase) (reverse reaction catalysed by phosphofructokinase)
- G6-P + H2O –> glucose + Pi (glucose 6-phosphatase) (reverse reaction catalysed by hexokinase)
Describe how Lactase activity is developmentally regulated in mammals
Lactase is active in all mammalian infants – their main nutrient in milk
After weaning lactase activity is down-regulated, since there is no more use for it
In some human cultures – mostly Europeans, where milk production from domesticated animals is a common practice, evolution has selected for the reactivation of lactase after infancy
However, about ⅔ of the world’s adults are lactose intolerant (eg majority of those with Chinese or Sub-Saharan Africans descent) due to the down-regulation of lactase
Lactase inactivity leads to the accumulation of lactose in the colon, where it is used as a favourite nutrient by bacteria that ferment it. This results in CO2 and H2 production – not a pleasant exercise
The medical term for this is lactose intolerance, and can be easily remedied by lactase ingestion or avoiding milk and some of its products
Describe the entry of fructose and galactose into glycolysis
The sugar nutrients enter the cells of different tissues from the blood.
They are converted to glycolytic intermediates to be metabolised.
Galactose converted to G6-P, process continues as normal
Fructose converted to F6-P by hexokinase then F1,6-BP, then to DHAP and GA3P which are metabolised to pyruvate the same way as GA3P arising from glucose
Describe how Glycogen is used for medium term energy storage
Glycogen metabolism is regulated – such as by the ‘flight and fight’ hormone adrenaline
Stored in the liver and the muscle of animals
Liver store used to replenish glucose levels in the blood, whereas the muscle store is used for local energy production
Good for quick energy needs when no food available because it can quickly generate glucose
Its ‘product’ glucose can be converted to energy in the absence of oxygen and is the source of energy for the brain
Describe how glycogen is broken down
Glycogen is highly branched to allow rapid breakdown from many 4’ OH ends
Glycogen phosphorylase cleaves the a-1,4 linked glucose units (a-1,4 glycosidic bonds - 90% of bonds in glycogen)
Glucose units are cleaved from the non-reducing end of the polymer - bond cleavage by addition of phosphate = phosphorolysis
The product of the reaction is glucose-1-phosphate and a one unit shorter glycogen chain
Breakdown of glycogen’s branches:
Phosphorylase stops 4 glucose units before a branching point. it cannot cleave a-1.6 glycosidic bonds (10% bonds in glycogen
Transferase transfers 3 units from the side branch to the main branch, exposing an a-1,6 link at the original branch point
a-1,6-glucosidase removes the glucose from the 1,6 linkage. Glucosidase produces glucose.
Glucose is then phosphorylated by hexokinase
In eukaryotes, transferase and a-1,6-glucosidase present in same polypeptide- a bifunctional enzyme
Glucose 1-phosphate is converted to glucose 6-phosphate by phosphoglucomutase - can enter glycolysis directly
Describe how glycogen’s breakdown products are fed into glycolysis
Products of glycogen breakdown:
glucose-1-phosphate ~90%
glucose ~10%
G1-P converted into G6-P by phosphoglucomutase
Glucose converted to G6-P by hexokinase
Where is glycogen broken down?
in the cytoplasm of the liver, muscle, brain and kidney cells
When is glycogen broken down/how is glycogenesis regulated?
When blood glucose levels drop, e.g. on fasting or starvation (liver)
When demand for glucose is very high (exercising muscle)
Signalled by high levels of the hormone glucagon (fasting) or adrenaline (exercise)
Adrenaline (in muscles) or glucagon (in liver) bind membrane receptor
1. G protein activation on hormone binding of receptor activates adenylate cyclase
2. Adenylate cyclase converts ATP to cAMP which activates protein kinase a (PKA)
3. PKA phosphorylates and activates phosphorylase from inactive ‘b’ form to active ‘a’ form - can now break down glycogen
The liver regulates glucose homeostasis in the whole body, whereas the muscle only requires energy for its own function.
muscle- energy levels
liver- glucose levels
What are the stages of processing fatty acids for energy?
Breakdown of triacylglycerol to fatty acids and glycerol in adipocytes
Activation of fatty acids and transport to mitochondria
Oxidation of fatty acids to acetyl CoA to feed the citric acid cycle
