MMT: glycolysis Flashcards
how much of our caloric burning comes from carbs?
50%
which enzymes are involved in the irreversible glycolysis steps?
hexokinase, PFK, pyruvate kinase
what enzyme in glycolysis is associated with the committed step?
PFK
why is lactate dehydrogenase important in terms of our energy production?
If we use up all of our NAD+ and have only NADH, glycolysis cannot continue. This is solved via lactate dehydrogenase. This allows NAD+ to be regenerated and allows the process of glycolysis to continue. It reduces pyruvate to lactate and oxidizes NADH to NAD+. This happens under anaerobic conditions.
what factors increase PFK1 activity? what factors decrease PFK1 activity?
increase PFK activity: high AMP/low ATP, low citrate, high fructose-2,6-bisphosphate, low protons, low lactate
decrease PFK activity: high ATP/low AMP, high citrate, high lactate, high amounts of protons
what factors increase pyruvate kinase activity? what factors decrease pyruvate kinase activity?
increase activity: high fructise 1,6 bisphosphate
decrease activity: high ATP
in the liver, what increases activity of pyruvate kinase?
dephosphorylation
describe the regulation of hexokinase
Inhibited via local control. When glucose-6-phosphate builds up, it inhibits hexokinase in order to stop the reaction of forming glucose-6-phosphate. It is also correlated with PFK regulation; Inactive PFK is going to lead to a buildup of fructose-6-phosphate, which will revert to glucose-6-phosphate.
Contrast the properties and physiological roles of hexokinase and glucokinase.
Glucokinase preforms the same function as hexokinase but is in the liver and pancreatic beta cells.
Hexokinase has a high affinity for glucose, while glucokinase’s affinity is lower. This allows the liver and pancreas to leave glucose in the bloodstream for tissues that need it. Glucokinase has a higher vmax, giving it a higher capacity to phosphorylate glucose. Glucokinase is induced by insulin so it can process high amounts of glucose in the blood.
Describe how mutations in glycolytic enzymes are associated with hereditary non- spherocytic hemolytic anemia
The RBCs will lyse because they have limited glycolysis function and can’t function as well. Tends to be issues with hexokinase, PGI, phosphoglycerte kinase, or pyruvate kinase (usually this one). Glucose-6-phosphate dehydrogenase can also largely be associated with this
Define the Warburg effect and its physiological significance
Cancer cells use glycolysis preferentially, making them excrete a lot of lactates. There isn’t a good explanation for this, thus it is called deranged metabolism. Even in the presence of oxygen, they prefer glycolysis. The theories for this are cancer cells shutting down mitochondria to prevent apoptosis, need to provide building blocks. We can use this effect to detect cancerous tissues. We use FDG to visualize these tissues in pet scans
Explain how arsenic poisoning affects ATP production in glycolysis.
Arsenic poisoning impacts the glycolytic process. It can impact G3P dehydrogenase by forming something other than 1,3 BPG. The arsenic gets removed and 3-phosphoglycerate is formed, skipping the ATP producing step. As a result, net ATP formation is 0
describe GLUT1 and GLUT3
GLUT1 and GLUT3 are basal transporters; they have low Km
describe GLUT2
GLUT2 is specific for liver and pancreatic; they need to sense the glucose concentration in the bloodstream to be able to manage the levels. GLUT2 has a high Km, meaning the only take glucose in when it is in abundance. This allows glucose to be left for other tissue types when not in high concentration
describe GLUT4
GLUT4 is mostly in muscle and fat cells. These cells are insulin dependent, which is because of GLUT4. They’re typically on vesicles inside the cells. In response to insulin the vesicles move to the cell surface. A lot of exercise increases this expression to get skeletal muscle more glucose
describe GLUT5: what it transports and where it is found
GLUT5 transports mostly fructose. Largely in the small intestine and adipose tissue.
What is the net rxn of glycolysis
Glucose + 2Pi + 2ADP + 2NAD»_space;> 2 pyruvate + 2ATP + 2NADH + 2H + 2H2O
What tissues depend on glycolysis
Skeletal muscle, kidney medulla, RBC, eyes, tumors
Describe the formation of 2,3-BPG and state its role in regulating the affinity of hemoglobin for oxygen in red blood cells.
It is an allosteric inhibitor of hemoglobin, meaning it lowers its affinity for oxygen allowing it to release oxygen to the tissues. It is held at high concentration in our red blood cells. We can dephosphorylate the molecule to increase hemoglobin affinity for oxygen.
what is the rapoport-luebering shunt?
used in RBCs to form 2,3-BPG using 1,3 BPG and 1,3BPG mutase. the shunt forms 2,3 BPG and skips the PGK step in glycolysis that amkes ATP. as a result, when using the shunt, we make net 0 ATP.
how do insulin/glucagon impact the synthesis of fructose 2,6-bisphosphate?
glucagon: causes PKA to phosphorylate PFK2, inactivating its kinase and activating its bisphosphatase. this leads to lowered fructose 2,6 bisphosphate and a less active PFK1.
insulin: causes PKA to dephosphorylate PFK2, activating its kinase and deactivating its bisphosphatase. this leads to increased fructose 2,6 bisphosphate and a more active PFK1.
if we have a lot of glucose, how does this impact PFK1?
PFK1 is supercharged to help really activate glycolysis and clear glucose from the bloodstream.
name the intermediates in glycolysis
- glucose
- glucose-6-phosphate
- fructose-6-phosphate
- fructose 1,6 bisphosphate
- glyceraldehyde-3-phosphate
- 1,3-bisphosphoglycerate
- phosphoenol pyruvate
- pyruvate
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name the enzymes in glycolysis
- hexokinase
- isomerase
- phosphofructokinase
- aldolase
- triose phosphate isomerase
- GL3P dehydrogenase
- phosphoglycerate kinase
- phosphoglycerate mutase
- enolase
- pyruvate kinase
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which steps of glycolysis produce ATP
phosphoenol pyruvate»_space; pyruvate using pyruvate kinase
1,3 bisphosphoglycerate»_space; 3 phosphoglycerate using phosphoglycerate kinase
which step of glycolysis produces NADH
glyceraldehyde-3-phosphate»_space; 1,3 bisphosphoglycerate using GL3P dehydrogenase
which two enzymes use ATP?
hexokinase and PFK
which enzyme has a thioester intermediate?
GAPDH (G3PDH)
which enzyme has an active-site histidine?
phosphoglycerate mutase
which series of enzymes produce an acid from an aldehyde?
GAPDH and PGK
which enzyme produces NADH?
GAPDH (G3PDH)
