Glycolysis Pathway Flashcards
Second step of glycolysis
Glucose-6-phosphate to Fructose-6-phosphate via phosphoglucose isomerase (isomerization reaction)
First step of glycolysis
D-Glucose to Glucose-6-phosphate via Hexokinase (or glucokinase in liver) and consumes ATP
What is the third step of glycolysis?
Fructose-6-phosphate to Fructose-1,6-bisphosphate via phophofructokinase-1 and ATP
What is the 4th step of glycolysis?
Fructossse-1,6-bisphosphate to either dihydroxyacetooone phosphate or glyceraldehyde 3-phosphate via aldolase
Dihydroxyacetone phosphate is isomerized…
By triose phosphate isomerase to glyceraldehyde 3-phosphate. This happens preferentially because glyceraldehyde 3-phosphate is being removed
What is the 5th step of glycolysis
Glyceraldehyde 3-phosphate is made into 1,3-Biphosphoglycerate via glyceraldehyde 3-phosphate dehydrogenase consuming a phosphate and making NADH and H from NAD
What is the 6th step of glycolysis
1,3-biphosphoglycerate to 3-phosphoglycerate via phosphoglycerate kinase making an ATP from ADP
7th step of glycolysis
3-phosphoglycerate to 2-phosphoglycerate by phosphoglycero-mutase
8th step of glycolysis
2-phosphoglycerate is made to phosphoenol-pyruvate via enolase and loss of water
What is the 9th step of glycolysis?
Phosphoenol-pyruvate is made to pyruvate via pyruvate kinaqse and production of ATP from ADP
What steps produce ATP via substrate level phosphoyrlation
1,3-biphosphoglycerate to 3-phosphoglycerate and phosphoenol-pyruvate to pyruvate
What two enzymes are part of the substrate level phosphoylation?
Phosphoglycerate kinase and pyruvate kinase
What step consumes ATP in glycolysis?
D-glucose to Glucose-6-phosphate
What enzyme requires ATP?
Hexokinase (or glucokinase in liver)
What are the three irreversible steps in glycolysis?
D-Glucose to glucose-6-phosphate; Fructose 6-phosphate to Fructose 1,6-biphosphate; Phophoenol-pyruvate to pyruvate
What step produces NADH + H?
Glyceraldehyde 3-phosphate to 1,3-biphosphoglycerate via glyceraldehyde 3-phosphate dehydrogenase
What enzyme is responsible for making NADH in glycolysis?
Glyceraldehyde 3-phosphate dehydrogenase
How many pyruvates are made per glucose molecule?
Two
What is the net production of ATP in glycolysis?
2 ATP per glucose (4 out-2 in)
What is the rate limiting step in glycolysis?
Fructose 6-phosphate to Fructose 1,6-biphosphate via PFK-1 and consuming ATP
What would be a morphological defect due to hexokinase mutation?
Anemia in RBC
What would be the result of Pyruvate kinase defect?
Probably lead to RBC anemia but also may contribute to increase in 2,3-BPG (everything above roadblock is accumulated and this is last step in glycolysis)
1,3-Bisphosphoglycerate can be made into what besides 3-phosphoglycerate?
Via mutase it van be made to 2,3-biphosphoglycerate.
2,3-bisphosphoglycerate is reintroduced to glycolysis how?
Via water and phosphotase into 3-phosphoglycerate
T or F: Production of 2,3-BPG and reintroduction via phosphotase at 3-phosphoglycerate level costs 1 ATP from glycolysis
T; skips the phosphoglycerate kinase step
T or F: The three irreversible steps of glycolysis are regulated by effector molecules and indirectly by hormones
T
What regulates glucokinase?
High Km of glucokinase is a self-regulator, no direct effector
What regulates hexokinase?
Accumulation of Glucose 6-phosphate (negative feedback inhibition)
Phosphofructokinase-1 is regulated by?
Positively: AMP, Fructose-2,6-P
Negatively: ATP, Citrate (lots of Krebs going on)
Pyruvate kinase is regulated by?
Positively: F-1,6-P
Negatively: Phosphoylation via cAMP-dependent pathways
Alanine (this is because alanine and pyruvate are interchangeable since they are isomers)
cAMP-dependent phosphorylation is important in regulating pyruvate kinase where?
In the liver, prevents consuming glucose when body needs it
Describe the cAMP cascade
Hormone hits receptor that is coupled to G-protein coupled receptor. Activates G-protein to release G-alpha from G-beta and gamma (GDP to GTP). This activates adenylyl cyclase to make ATP into cAMP
What enzyme is responsible for making cAMP from ATP?
Adenylyl cyclase
Describe the structure of G-protein?
Alpha,beta, and gamma subunits.
Compare and contrast active and inactive G-protein
Inactive: All three subunits together, alpha linked to GDP
Active: Alpha separates from gamma and beta when Alpha is conjoined with GTP
Describe the function of cAMP
cAMP interacts with cAMP-dependent protein kinase A (makes catalytic subunits active by phosphorylating the regulatory subunits) which then phoysphorylates protein substrates leading to intracellular effects. Turned off by protein phosphatases.
What happens in the liver when high glucose?
High glucose=high insulin=low cAMP=low PKA=low phoshporylation of PFK2=high activity of PFK2=high F2,6BP production which activates glycolysis
What happens in the liver with low glucose?
Low Blood sugar=cAMP cascade=PFK2 is phosphorylated to be inactive=little F2,6BP produced=Gylcolysis is not activated
T or F: Insulin opposes the cAMP cascade
T
Describe the process of insulin triggered cell response
Insulin binds receptor and subunits phosphorylate themselves at tyrosine residues, the subunits also phosphorylate other protein kinases to produce cellular response of reversal of glucagon and stimulation of glucose transport via GLUT4
Describe the structure of PFK-2
Bound to FBP-2. When phosphorylated, PFK-2 is inactive and FBP-2 is active (bifunctional enzyme).
What happens from a regulatory stance of PFK-1 when insulin is high and glucagon is low?
Low glucagon means little cAMP production. High insulin means reduced levels of active PKA leading to dephosphorylation of PFK2 leading to activation of the Fructose 6-phosphate to Fructose 2,6-bisphosphate pathway.
T or F: Insulin increases glycolysis
T
T or F: Elevated levels of Fructose 2,6-biphosphate increase PFK-1 activity
T
In humans, what three products can pyruvate be converted to following glycolysis?
Lactate, Acetyl CoA, and Oxaloacetate
How is pyruvate converted to lactate?
By lactate dehydrogenase, regenerates NAD from NADH and H
Describe an instance where lactate is produced
Decreased O2, less ATP, inc lactate, H accumulated
How is pyruvate made to acetyl CoA?
Pyruvate dehydrogenase complex
T or F: pyruvate to lactate is reversible
T
What regulates Pyruvate dehydrogenase?
Inhibited: Acetyl CoA
Is source of acetyl CoA for krebs and fatty acid synthesis
How is pyruvate made into oxaloacetate?
Pyruvate carboxylase consumes CO2 to replenish TCA cycle intermediates
Pyruvate carboxylate does?
Activated by Acetyl CoA and replenishes TCA intermediates, provides substrates for gluconeogenesis
What is the net yield of NADH when glucose 6-phosphate is converted to lactate by anaerobic glycolysis?
0
The committed step of glycolysis is?
PFK-1 step