Glycolysis Flashcards
What are the 2 types of metabolic pathways?
Catabolic and Anabolic
Which pathway is this?:
-where the energy yielding macromolecules are broken down into simple molecules which will undergo complete breakdown to yield energy poor end products, during this process they will produce energy rich molecules like ATP and NADH+H, FADH2.
Catabolic
Which pathway is this?:
-where the simple molecules either synthesized with in the cells or derived from the diet will combine to form macromolecules. During this process the energy is consumed and the energy required for these pathways will be given by the energy produced by catabolic pathways.
Metabolic
What does one molecule of glucose generate?
2 pyruvate
In general, what is the net yield from glycolysis if the cell has mitochondria?
8 net ATP
What is the net yield from glycolysis under anaerobic conditions?
2 ATP and 2 lactate.
What are the 3 enzymes in glycolysis that catalyze irreversible reactions?
- Hexokinase/glucokinase
- Phosphofructokinase-1
- Pyruvate Kinase
What is the rate-limiting enzyme for glycolysis?
Phosphofructokinase-1
What enzyme catalyzes the only oxidation reduction reaction in glycolysis?
Glyceraldehyde 3-phosphate dehydrogenase
Deficiency of what enzyme leads to hemolytic anemia?
Pyruvate kinase
Which is present in most tissues?
hexokinase
Which is present in hepatocytes and beta-cells of the pancreas?
glucokinase
What is one form of MODY due to?
mutation of the pancreatic glucokinase gene
What are the 2 different gates of pyruvate?
- In nonproliferating cells, in the presence of O2 and mitochondria, pyruvate enters into TCA cycle as acetyl CoA.
- Anaerobic glycolysis: decreased O2 and no mitochondria, pyruvate forms lactate.
What is invested in the energy investment phase of glycolysis?
2 ATPs
What is generated in the energy generation phase of glycolysis?
4 ATPs, 2 NADH, and 2 pyruvate molecules
What enzyme does fluroride inhibit and hence causes a decrease in glycolysis?
enolase
What enzyme catalyzes the substrate level phosphorylation resulting in ATP production at a substrate level and is one of the regulated enzymes?
Pyruvate kinase
how is hemolyctic anemia caused?
-when glycolysis levels decrease, ATP decreases, and RBCs can’t maintain the membrane, so they rupture
What is the glycolysis pathway?
- D-glucose is converted irreversibly to glucose-6-phosphate by hexokinase/glucokinase ->
- glucose-6-P is converted to fructose-6-phosphate by phosphoglucose isomerase ->
- Fructose-6-P is irreversibly converted to Fructose-1,6-bisphosphate by phosphofructokinase ->
- Fructose-1,6-bisphosphate is converted to dihydroxyacetone phosphate by aldolase ->
- dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate by triose phosphate isomerase ->
- glyceraldehyde-3-phosphate is converted to 1,3-bisphosphoglycerate by glyceraldehyde-3-phosphate dehydrogenase ->
- 1,3-bisphosphoglycerate is converted to 3-phospoglycerate by phosphoglycerate kinase ->
- 3-phospoglycerate is converted to 2-phosphoglycerate by phosphoglyceromutase ->
- 2-phosphoglycerate is converted to phosphoenol-pyruvate by removal of H2O ->
- phosphoenol-pyruvate is converted to pyruvate by pyruvate kinase
Which has a low km and vmax for glucose?
hexokinase
What acts as a glucose sensor in the maintenance of blood glucose homeostasis?
Glucokinase
What does measuring c-peptide show?
Measuring c-peptide shows the amount of endogenous insulin when exogenous insulin is taken
What are negative allosteric modulators of PFK-1?
ATP and citrate
What are the positive modulators of PFK-1?
AMP and fructose 2,6-bis-phosphate
What stimulates PFK-1? What inhibits it?
Insulin stimulates and glucagon inhibits PFK-1
What does PFK-2 kinase do?
it is activated by insulin to keep PFK-2 in dephosphoylated form and increase the conversion of Fru-6-P to Fru-2,6-bisphos, which is the pos. allosteric modulator of PFK-1
What does PFK-2 phosphatase do?
fructose bisphosphatase-2 is activated by glucagon by keeping PFK-2 in phosphorylated form the active PFK-2 phosphatase (FBP-2) will convert Fru-2,6-bisphosphate to Fru-6-phosphate, this will decrease the levels of Fru-2,6-bisphosphate, hence its positive influence on PFK-1 weans off.
What is aldolase?
it is a lyase class of enzyme that breaks F1,6-BP
What does a deficiency of aldolase B lead to?
hereditary fructose intolerance
how many types of aldolases are there?
3
What does glyceraldehyde 3-phosphate dehydrogenase produce?
NADH+H
What role does Arsenic play?
it prevents net ATP and NADH production by glycolysis, without inhibiting the glycolysis pathway
What is the most common glycolytic enzyme deficiency leading to hemolytic anemia?
pyruvate kinase deficiency
What is the second most common cause for genetic enzyme deficiency, leading to hemolytic anemia?
pyruvate kinase deficiency
What is pyruvate kinase deficiency characterized by?
- increase in 2,3-BPG and lower than normal oxygen affinity of HbA
- mild to moderate chronic hemolytic anemia compared to G6PD deficiency
- absence of Heinz bodies
Where is the ratio of NADH/NAD+ lower, liver and heart or skeletal muscle? Why?
liver and heart, these tissues oxidize lactate (obtained from the blood) to pyruvate
What is the major fuel for the heart contraction?
ATP from lipids/FAs
What is the Warburg effect?
The Warburg effect is the enhanced conversion of glucose to lactate observed in tumor cells, even in the presence of normal levels of oxygen.
~aerobic glycolysis
What does anaerobic glycolysis yield?
2 ATP per glucose by substrate-level phosphorylation
What does aerobic glycolysis yield?
net 2 ATP per glucose plus 2 NADH+ 2H per glucose that can be utilized for ATP production in the mitochondria
Cytoplasmic NADH oxidized using the malate shuttle produces what?
a mitochondrial NADH and yields approximately 3 ATP by oxidative phosphorylation.
-38 total
Cytoplasmic NADH oxidized using the glycerol phosphate shuttle produces what?
a mitochondrial FADH2 and yields approximately 2 ATP by oxidative phosphorylation.
-36 total
What is D-glucose converted to glucose-6-phosphate by?
irreversibley by hexokinase/glucokinase
What is glucose-6-P converted to fructose-6-phosphate by?
phosphoglucose isomerase
What is Fructose-6-P converted to Fructose-1,6-bisphosphate by?
irreversibly by phosphofructokinase
What is Fructose-1,6-bisphosphate converted to dihydroxyacetone phosphate by?
aldolase
What is dihydroxyacetone phosphate converted to glyceraldehyde-3-phosphate by?
triose phosphate isomerase
What is glyceraldehyde-3-phosphate converted to 1,3-bisphosphoglycerate by?
glyceraldehyde-3-phosphate dehydrogenase
What is 1,3-bisphosphoglycerate converted to 3-phospoglycerate by?
phosphoglycerate kinase
What is 3-phospoglycerate converted to 2-phosphoglycerate by?
phosphoglyceromutase
What is 2-phosphoglycerate converted to phosphoenol-pyruvate by?
removal of H2O
What is phosphoenol-pyruvate converted to pyruvate by?
pyruvate kinase
What is hexokinase inhibited by?
reaction product glucose-6-phosphate
what is glucokinase induced by? is it inhibited by glucose-6-phosphate?
it is induced by insulin in hepatocytes and is not inhibited by glucose-6-phosphate
Fructose 2,6-bisphosphate is produced by?
PFK-2
What does aldolase B do?
Breaks Fructose 1,6-bisphosphate and fructose-1-phosphate in liber and kidney
What does fluoride inhibit?
Enolase