9. Glycolysis and Glucose Oxidation Flashcards
What is it called if there’s excess/too little glucose in the blood?
How much of the blood glucose does the brain use?
Roughly how much glucose is circulating in your blood?
Hyperglycemic/hypoglycemic
60%
4g
What happens to glucose when it is transported into the cell?
What are the 3 different possible pathways folowing this?
How is glucose taken up
Converted to glucose-6-phosphate
1) Converted to pyruvate in glycolysis (body can also make glucose-6-phosphate from pyruvate via gluconeogenesis)
2) Pentose phosphate pathway (uses C and energy in sugar for biosynthesis)
3) Can store glucose in form of glycogen
Facilitated transport across a membrane - there are 12 glucose transporters (GLUT)
Describe the following glucose transporters:
a) GLUT1
b) GLUT2
c) GLUT4
a) works all the time, low Km (works best at low conc of glucose but saturated at high concs). Provides basic amount of glucose entering cells, like basal level
b) liver/pancreas glucose uptake, high Km. Pancreas produces insulin and glucagon and liver controls blood glucose, so a high Km allows these cells to respond to high glucose levels
c) glucose uptake in muscle/adipose (low Km), number of GLUT4 in membrane controlled by insulin - changes ability to take up glucose from blood to muscle/adipose
What 2 forms can GLUT4 exist in?
How does insulin work on one of these forms?
How is this linked to exercise?
In membrane or in small spherical vesicles in cell.
Insulin action recruits GLUT4 to membrane, increasing the amount of glucose entering muscle/adipose tissue and lowering BG.
More exercise = more GLUT4 in membrane b/c muscle needs more energy
What happens to glucose once it is transported into the cell?
How does feedback control this process
How is the liver and pancreas different?
Describe the control of GK.
It’s phosphorylated (using 1 ATP) by hexokinase (low Km) to glucose-6-phosphate so it can’t leave the cell (LIVER and PANCREAS= EXCEPTION).
High glucose-6-phosphate levels inhibit hexokinase
Liver has glucokinase which catalyses the same reaction as HK. It has a high Km and doesn’t have feedback inhibition like HK, so allows glucose storage when high levels, and pancreas to sense high levels and release insulin/glucagon.
Controlled by its location in the cell - when BG low GK bound to GKRP (regulatory protein) in the cell nucleus. When BG high, released into cytoplasm = active. In pancreas = beta cells act as sensor.
Mutations in GK/GKRP can predispose people to diabetes
What is the next step following glucose conversion to glucose-3-phosphate?
What happens next?
Molecule rearrangement (to rearrange energy and make it easier for the next steps) = fructose-6-phosphate. ISOMERISATION REACTION.
PFK-1 (phosphofructokinase 1) converts F-6-P to fructose-1,6-bisphosphate. This is the main regulatory step of glycolysis - can turn it off and on. Uses ATP but high levels of ATP inhibit PFK-1. If AMP/ADP levels are high = turns on glycolysis.
What 3 things regulate the activity of PFK-1?
What is PFK-2?
What happens to the formed fructose-1,6-bisphosphate?
ATP levels (high levels inhibit), Fructose-2,6-bisphosphate (promotes PFK-1 activity), Citrate (high levels inhibit b/c suggest already have lots of energy)
Produces fructose-2,6-bisphosphate which controls PFK-1. If have high levels of glucose-> get fructose-6-P and PFK-2 produces more fructose-2,6-bisphosphate which activates the main pathway -> glycolysis!
Cleaved to 2 3C products: dihydroxyacetone phosphate and glyceraldehyde-3-phosphate
What happens to the dihydroxyacetone phosphate?
Interconverted to glyceraldehyde-3-phosphate
What happens to glyceraldehyde-3-phosphate?
What is the ATP output of glycolysis?
Substrate level phosphorylation! Converted to 1,3-bisphosphate glycerate -> first ATP produced as it’s converted to 3-phosphogycerate by phosphoglycerate kinase. Then converted to phosphoenolphyruvate (PEP), and then pyruvate kinase removes P from PEP to make pyruvate and ATP.
Produced 4 ATP so far so net gain of 2 ATP.
Where is the reduced NAD produced?
Why does it need to be regeneated?
How reduced NAD this regenerated to oxidised NAD+?
How does pH affect glycolysis enzymes in muscles?
During 1st substrate level phosphorylation (glyceraldehyde 3 phosphate -> 1,3 bisphosphoglycerate)
Finite amount of NAD in cell
Aerobic conditions: feeds into respiratory chain -> ETC
Anaerobic/cells without mitochondria: regenerated by forming lactate. Lactate is acidic (reduces pH in muscles)
If more acidic, glycolysis is inhibited = safety mechanism to stop body becoming too acidic.
Where does glycerol come from?
How can it be used for substrate entry in glycolysis?
Fat (triglyceride = 3FA and 1 glycerol). Formed from breakdown of fat, some dietary, majority from body adipose stores.
Metabolised into the liver: glycerol kinase converts it to glycerol 3 phosphate, then it’s oxidised (producing NADH) to dihydroxyacetone phosphate. Can then be converted to glyceraldehyde-3-phosphate —–> pyruvate
Mainly happens in liver so liver mainly responsible for glyceral disposal
Where does fructose come from?
How can it feed into glycolysis?
Common sugar in diet (sweeter than glucose)
It can be metabolised by hexokinase to F-6-P but not the main path b/c HK not that active towards fructose. Instead main path in liver: Fructokinase converts fructose to fructose-1-phoshpate, then aldolase B converts it to dihydroxyacetone phosphate and glyceraldehyde (which can be converted to glyceraldehyde-3-phosphate)
What is the pentose phosphate pathway?
Where can PPP products (which ones?) be fed back to?
What is the difference between NAD and NADP?
An alturnative pathway from glucose-6-phosphate. Important for biosynthesis, creating the required NADPH required for fat and steroid hormone synthesis. And nucleotide biosynthesis.
Glycolysis as fructose-6-phosphate and glyceraldehyde-3-phosphate
NAD: used for energy metabolism - moving e- around
NADP: carries around e- for building things, made in PPP
