EXAM3_L30_Glycolysis Flashcards
What 2 things in the LIVER serves as the glucose sensor for insulin release?
- GLUT2 beta cell glucose sensor
2. Glucokinase
Where is energy invested in glycolysis?
Step 1 (hexokinase) one atp Step 3 (PFK-1) one atp
Where is energy generation phase of glycolysis?
Step 6 (2 NADH) Glycerol-3PDH Step 7 (2 ATP) Phosphoglycerate Step 10 (2 ATP) Pyruvate Kinase
Anaerobic glycolysis occurs in cells with no/few mitochondria. What are the reactants and products?
(RBC, Lens, Kidney medulla)
Glucose + 2 ADP + 2Pi > 2 Lactate + 2ATP
GLUT 1,2,3,4 transporters
describe 1,3
describe 2
describe 4
1 & 3 have high affinity for glucose & found in most cells
Glut2 beta cell glucose sensor of insulin (liver & Pancreas)
Glut4 (Muscle & adipose) - needs insulin signal
What irreversible steps in glycolysis? what enzyme each?
1,3,10
1- hexokinase
3- PFK1
10- Pyruvate Kinase
What enzyme used for lactate?
Lactate dehydrogenase (not regulatory)- goes both ways
Glucokinase vs Hexokinase
Glucokinase high Vmax/Km - liver pancreas
Hexokinase Low Vmax/Km- most cells
Permanent neonatal diabetes mellitus (PNDM)
aka: defective glucose sensing mechanism
Mutation of NO glucokinase
- No C peptide detected
- Develop Hyperglycemia, diabetic ketoacidosis, retardation
PFK1- Allosteric regulated
Activated by?
Inhibited by?
Activated by AMP + Fructose 2,6-Bisphosphate
Inhibited by ATP + Citrate in the Cytosol
- means too much and was exported the mitochondria into the cytosol (needs to slow it down)
AMP and fructose2,6bisP do what?
Activate PFK1 in glycolysis
High levels of ATP and Citrate in the cytosol do what?
Inhibit PFK1 in glycolysis
High IG ratio causes decreased cAMP and thus decreases PKA activity
When PKA activity is low what is the effect on PFK2/FBP2 complex?
PFK2/FBP2 complex becomes DEphosphorylated
PFK2 is activated and forms F2,6-BisP
F2,6-BisP:
ACTIVATES: (PFK-1) and thus GLYCOLYSIS and
INHIBITS: (FBPase-1) and thus GLUCONEOGENESIS
How does High IG ratio stimulate glycolysis?
3 steps
- High IG inhibits cAMP and PFK.
- PFK2/FBP2 complex dephosphorylated» Active PFK2
- Forms F2,6-BisP: Activates PFK1 (glycolysis)
Inhibits FBPase1 (gluconeogenesis)
How does high IG affect Pyruvate Kinase?
INSULIN DEPHOSPHORYLATES TARGET ENZYMES:
- F1,6BisP dephosphorylated (now ACTIVE) and activates Pyruvate Kinase
How does Low IG affect Pyruvate Kinase?
GLUCAGON PHOSPHORYLATES TARGET ENZYMES:
GalphaS-GPCR> cAMP > increased PKA activity (aka phosphorylation)
F1,6BisP inhibited by phosphorylation & Pyruvate kinase inactive
Step 11 converts Lactate via LDH (Anaerobic Glycolysis)
What happens?
Pyruvate is reduced by NADH to Lactate in the cytosol
and regenerates NAD+
(remember we need 700:1 NAD+) to continue glycolysis
Why is regenerating NAD+ so vital to glycolysis?
NAD+ required for step 6 and for glycolysis to continue
Step 11 is called anaerobic glycolysis. What is converted?
Pyruvate is converted to LACTATE by LD
- Regenerates NAD+ (for step 6)
(NAD+ Critical for glycolysis to continue)
Lactic acidosis occurs when circulatory Hypoxia
(mi, pe, hemorrhage etc. ) Why?
increased AMP > Activates PFK1> Glycolysis > Lactic Acid
DHAP (dihydroxyacetone-P) Used in Liver and adipose tissue for TAG synthesis- what enzyme ? what does it turn into?
G3PDH- makes glycerol 3 phosphate (backbone for TAG)
part of glycerol-3P shuttle ? idk what that means?
What are the two steps that generate ATP by Substrate level phosphorylation?
What enzymes do they use?
Step 7 (1,3-BPG) Step 10 (PEP)
These are High energy intermediates used to make ATP
What 2 enzymes produces ATP in glycolysis?
- Phosphoglycerate Kinase
- Pyruvate Kinase
Phosglycerate Kinase= 1,3-BPG (substrate Level Phosphor)
Pyruvate Kinase= PEP (substrate Level Phosphorylation)
What are the glycolytic end products ?
ATP (via phosphoglycerate kinase & pyruvate kinase)
(sublevPhos- 1,3BPG & PEP)
PYRUVATE
NADH (Glyceraldehyde3PDH req. Pi +NAD+)
In step 6 NADH is generated by what enzyme? and what are the required substrates?
Glyceraldehyde-3 Phosphate Dehydrogenase (G3PDH)
requires Pi & NAD+
In AEROBIC how is NAD+ regenerated from NADH?
What two Ways? Where do they occur?
- Glycerol-3P Shuttle (NADH > FADH2 inner mito memb)
2. Malate-Aspartate shuttle (NADH>NADH IM-matrix)
Pyruvate is pumped into the inner mitochondrial matrix by what type of Transport?
Secondary Active Transport using H+ gradient from ETC
Pyruvate + CoA + NAD+ are converted to what?
Acetyl CoA + NADH + H+ +CO2
What is PDHC inhibited by?
Products: NADH (ETC overload or low oxygen) + Acetyl CoA (TCA backed up)
5 Coenzymes of PDHC and their required Vitamin Precursors?
TPP- thiamine B1 FAD- riboflavin B2 NAD+ Niacin B3 CoA- Pantothenate B5 Lipoic Acid (None)