Topic 5: Glycolysis Flashcards
What is the major source of carbs?
Sun –> Plants make carbs with light + CO2 + H2O
How is glycogen organized?
alpha-1,4 linkages with alpha-1,6 branches roughly every 10 residues
What is “normal” glucose levels in non-ruminants?
70-120 mg/dl or 4.16-6.66 mM
What is normal glucose for Bovines and other ruminants?
40-75mg/dl AND they don’t normally have a glucose spike after a meal since microbes get it all
What is more condensed? Starch or glycogen?
Glycogen. They branch roughly every 10 residues whereas Starch branches every 30 residues.
How is starch organized?
alpha-1,4 linkages with alpha-1,6 branches roughly every 30 residues
What is the advantage of storing in polymeric forms such as starch and glycogen?
Reduces OSMOTIC pressure. Remember osmotic pressure depends on number of molecules not size.
What glucose transporters are insulin sensitive and what tissues are they in?
GLUT-4 and they are in: Skeletal Muscle, Heart, and Fat Cells
Which tissues have GLUT 2?
Liver and Pancreas and they have a SHITLOAD. Liver is considered freely permeable to glucose. These are always present an essential for normal metabolism.
have a High Km for Glucose
Which tissues have GLUT 1 and 3 and why is it significant?
Brain (GLUT 1 and 3), Placenta (GLUT 1 and 3), RBCs (GLUT 1), Colon (GLUT 1)
They have a lower Km for glucose than the other GLUTs which means they will MUCH MORE readily take up glucose.
What is the definition of Km?
The concentration of solute at which an enzyme will be 50% saturated. A lower Km means the enzyme will take up more solute at lower concentrations.
Which tissues have GLUT 5?
GLUT 5 is a fructose transporter so you see it in the small intestines and testis but also less extensively in skeletal muscle, kidney, adipose and the brain.
Where do you see SGLTs and what are they?
Glucose/Na+ Symports
Seen in the gut and kidney.
What is the difference between hexokinase and glucokinase with respect to Km for glucose and tissue location?
Hexokinase has a lower Km and is EVERYWHERE.
Glucokinase has a higher Km and is in the Liver, Pancreas, Brain and Gut. It is activated in higher concentrations of glucose
What happens in Step 1 of Glycolysis?
Glucose is phosphorylated via hexokinase or glucokinase (tissue and [Glucose] dependent) to Glucose-6-phosphate
ATP is used here.
What happens in Step 2 of Glycolysis?
Glucose-6-phosphate via phosphoglucose isomerase is slightly rearranged to Fructose-6-phosphate
What happens in Step 3 of Glycolysis?
Fructose-6-phosphate is phosphorylated by Phosphofructokinase (PFK) to become Fructose-1,6-bisphosphate
ATP is used here.
What happens in Step 4 of Glycolysis?
F-1,6-P via Aldolase split up into 2 units: Dihydroxyacetone (DHAP) and Glyceraldehyde-3-Phosphate (GA3P)
The two can be converted interchangeably by triose phosphate isomerase. (triose for 3 C sugars involved, phosphate for each having a single phosphate, isomerase since they are isomers)
What happens in Step 5 of Glycolysis?
GA3P via GA3P-Dehydrogenase is phosphorylated into 1,3-bisphophoglycerate
NADH and a free H+ are generated here.
What happens in Step 6 of Glycolysis?
1,3-BPG loses a phosphate to ATP via phosphoglycerate kinase to become 3-Phosphoglycerate.
ATP is generated here.
What happens in Step 7 of Glycolysis?
The phosphate on 3-Phosphoglycerate is rearranged via phosphoglyeromutase to become 2-phosphoglycerate.
What happens in Step 8 of Glycolysis?
2-Phosphoglycerate has an H2O removed by ENOLASE to become Phosphoenolpyruvate (PEP).
H2O is yielded here.
What happens in Step 9 of Glycolysis?
PEP via Pyruvate Kinase loses a phosphate to ATP to become pyruvate.
ATP is generated here.
This step is TOTALLY IRREVERSIBLE and considered the rate limiting step.
What is the significance of the action of hexokinase and glucokinase?
Glucose Trapping! Once glucose is phosphorylated by one of these enzymes it cannot get out of the cell.
Hexokinase is constitutive while Glucokinase has a much higher Km.
Glucokinase is also induced by insulin –> Double Trap!
Insulin isn’t released until high [glucose] is detected at the same time high [glucose] triggers its activation.
Compare and Contrast Hexokinase and Glucokinase
Hexokinase: Low Km for glucose; in EVERY tissue; unaffected by insulin; feedback inhibition by its product, Glucose-6-Phosphate
Glucokinase: High Km for glucose; only in Liver, Pancreas, Brain and Gut; NO feedback inhibition; induced by insulin!
Why is HYPERGLYCEMIA bad?
Glucose is an ALDEHYDE SUGAR – VERY Reactive
In the CNS, because they are highly reactive, they tend to form crosslinks –> they Bind and will spontaneously add themselves to molecules especially PROTEINS
Glycosylated Proteins at a rate faster than can be corrected. Changing their structure changes their function. Extremeties take the biggest hit, FEET most common and Fingers.
Glycosylated axons will no longer carry depolarizations ==> NEUROPATHY
Kidneys will also take a hit -> Kidney failure in diabetics. Mess up endothelium of capillary surfaces.
Reduced circulation and innervation can lead to no sensation of gangrene onset
Why is hypoglycemia bad?
Glucose is fuel for the body. Everyone needs it. Not enough = you’re fucked. Have a nice day!
