MODULE 9: Chapter 9.4 Flashcards
What factors control flux through all metabolic pathways?
Substrate availability and levels of catalytic activity
These factors influence enzyme activity and metabolic reactions.
What defines reversible reactions in metabolic pathways?
Reactions that operate at ΔG values close to zero
The direction of metabolic flux for these reactions depends on substrate availability.
Which three enzymes in glycolysis are functionally irreversible?
- Hexokinase (reaction 1)
- Phosphofructokinase-1 (reaction 3)
- Pyruvate kinase (reaction 10)
These enzymes are subject to enzymatic control due to physiologic metabolite concentrations.
What are rate-limiting reactions in a metabolic pathway?
Reactions that proceed at the lowest rate compared to other reactions in the pathway
They often involve low enzyme activity even with high substrate levels.
What distinguishes glycolysis from gluconeogenesis?
Glycolysis is a catabolic pathway yielding 2 net ATP, while gluconeogenesis is an anabolic pathway consuming 4 ATP and 2 GTP
Both pathways share reversible steps but differ in their irreversible steps and energy requirements.
What is the ΔG°’ value for glycolysis?
-85.0 kJ/mol
This value indicates that glycolysis is a favorable pathway.
What is the ΔG°’ value for gluconeogenesis?
-47.6 kJ/mol
This value indicates that gluconeogenesis is also a favorable pathway, though less so than glycolysis.
What is the role of glucokinase in liver and pancreatic cells?
Acts as a molecular sensor of high blood glucose levels
It phosphorylates glucose to form glucose-6-P, trapping glucose within the cell.
How does glucokinase differ from hexokinase?
- Glucokinase has a low affinity for glucose (Km ∼10 mM)
- Hexokinase has a high affinity for glucose (Km ∼0.1 mM)
- Glucokinase is not inhibited by glucose-6-P
These differences ensure effective glucose regulation in the liver.
What happens to glucokinase activity after a carbohydrate-rich meal?
Significant levels of glucose phosphorylation by glucokinase occur
This helps sequester glucose for glycogen storage.
What triggers insulin release from pancreatic β cells?
Increased flux through glycolysis due to elevated blood glucose levels and glucokinase activity
This process involves several steps including membrane depolarization and calcium influx.
What are the allosteric regulators of phosphofructokinase-1 (PFK-1)?
- Activators: AMP, ADP, fructose-2,6-bisphosphate
- Inhibitors: ATP, citrate
These regulators influence PFK-1 activity based on the energy charge of the cell.
What conformations does PFK-1 exist in?
- Inactive T-state conformation (high ATP concentration)
- Active R-state conformation (high AMP or ADP concentration)
The conformation affects the enzyme’s affinity for fructose-6-P.
What stabilizes the active conformation of pyruvate kinase?
Binding of fructose-1,6-bisphosphate
This is an example of feed-forward regulation indicating increased substrate levels upstream.
How does ATP affect pyruvate kinase activity?
ATP acts as an allosteric inhibitor, decreasing flux through the glycolytic pathway
This leads to elevated levels of glucose in liver and muscle cells.
What does the term ‘energy charge’ refer to?
The ratio of ATP, ADP, and AMP concentrations in the cell
It reflects the energy available from phosphoanhydride hydrolysis.
What happens to glucose levels in liver and muscle cells when flux through the glycolytic pathway decreases?
Elevated levels of glucose are converted to glycogen as a storage form of metabolic energy.
What regulates pyruvate kinase activity in the glycolytic pathway?
Activated by fructose-1,6-bisphosphate and inhibited by ATP.
How does fructose-1,6-bisphosphate affect pyruvate kinase?
Stabilizes the active tetrameric form of pyruvate kinase by binding to allosteric effector sites.
What is the role of α-amylase in carbohydrate digestion?
Breaks down dietary starch into the disaccharide maltose.
What are the products of maltose cleavage by maltase?
Two molecules of glucose.
How are disaccharides sucrose and lactose cleaved into monosaccharides?
By hydrolytic enzymes sucrase and lactase, respectively.
What is the result of lactose digestion by lactase?
Conversion into galactose and glucose.
What symptoms do individuals with lactose intolerance experience?
Excessive flatulence and diarrhea.
What causes the intestinal symptoms of lactose intolerance?
Activity of anaerobic bacteria fermenting undigested lactose.
How does glycerol enter the glycolytic pathway?
Through a two-step reaction involving glycerol kinase and glycerol-3-phosphate dehydrogenase.
What is the first step of fructose metabolism in liver cells?
Conversion to fructose-1-phosphate by fructokinase.
What are the end products of fructose metabolism in liver cells?
Dihydroxyacetone-P and glyceraldehyde.
What is the effect of fructose intolerance on individuals?
Buildup of fructose-1-P leading to toxicity.
What is the first enzymatic step in galactose metabolism?
Phosphorylation of galactose by galactokinase to form galactose-1-phosphate.
What condition is caused by defects in galactose-1-P uridylyltransferase?
Galactosemia.
What are the consequences of galactosemia in infants?
Developmental disabilities and liver damage.
What do glycolytic intermediates provide for anabolic pathways?
Carbon skeletons for biosynthesis.
What is the role of glucose-6-P in anabolic pathways?
Converted to glucose-1-P for glycogen synthesis.
What stimulates PFK-1 activity?
Fructose-2,6-bisphosphate.
What are the three irreversible reactions in glycolysis?
Catalyzed by hexokinase, PFK-1, and pyruvate kinase.
What signals low energy charge in the cell?
AMP, ADP, and fructose-2,6-BP.
What signals high energy charge in the cell?
ATP and citrate.
How does allosteric regulation affect enzyme activity?
Allows dramatic increases or decreases in activity over narrow substrate concentration ranges.
How many net moles of ATP can be generated from 2 moles of lactose under anaerobic conditions by infants?
4 moles of ATP.
What is lactose intolerance?
A condition caused by decreased expression of lactase.
What is fructose intolerance?
A genetic malady caused by the inability to make aldolase B.
What is galactosemia?
A genetic defect that blocks the conversion of galactose to glucose.
What is a rate limiting step in a metabolic pathway?
An essentially irreversible reaction step that can be tightly controlled.
