What are the energy-expending steps of glycolysis and what energy molecules are expended?
Energy-expending steps in the preparatory phase of glycolysis are the following:
- 1 ATP per glucose: Glucose → G6P
- 1 ATP per glucose: Fructose-6-phosphate → F1,6BP
After hexokinase forms glucose-6-phosphate (G6P), what is the next compound formed in glycolysis?
Step 2 (preparatory): G6P is isomerized to fructose-6-phosphate (F6P) by phosphoglucose isomerase. This is a fully reversible reaction driven in either direction by relative concentrations of the substrates.
Gene mutations in which glycolytic enzyme can be a cause of maturity-onset diabetes of the young (MODY)?
Gene mutations in glucokinase can be a cause of maturity-onset diabetes of the young (MODY). MODY can present as familial diabetes or gestational diabetes, as well as diabetes with an atypical presentation (e.g. a slim, relatively fit type 2 diabetic).
The synthesis of which of the following glycolytic intermediates directly requires ATP?
B) Dihydroxyacetone phosphate
D) Glyceraldehyde 3-phosphate
In glycolysis, only 2 steps consume ATP:
- the synthesis of glucose-6-phosphate from glucose, and
- the synthesis of F1,6BP from fructose-6-phosphate.
F6P is made from G6P via an isomerase and doesn’t consume energy.
After fructose-1,6-bisphosphate is formed, what is the next compound formed in glycolysis?
Step 4 (preparatory): The unstable F1,6BP is split by aldolase to yield two molecules of the 3-carbon glyceraldehyde 3-phosphate (GA3P).
In reality, fructose is split into GA3P + DHAP (dihydroxyacetone phosphate), but DHAP is rapidly isomerized to GA3P.
After 1,3-bisphosphoglycerate (1,3BPG) is formed, what is the next compound formed in glycolysis?
Step 6 (payoff): 1,3BPG is dephosphorylated, yielding 3-phosphoglycerate (3-PG).
In what cellular compartment does glycolysis occur?
Glycolysis occurs in the cytosol and has 2 phases: preparatory (requires energy) and payoff (generates energy).
After fructose-6-phosphate is formed, what is the next compound formed in glycolysis?
Step 3 (preparatory): F6P is phosphorylated to fructose-1,6-bisphosphate (F1,6BP) by phosphofructokinase-1 (PFK-1).
What are the energy-yielding steps of glycolysis and what energy molecules are formed?
Energy-yielding steps in the payoff phase of glycolysis are the following:
- 2 NADH per glucose: GA3P → 1,3BPG
- 2 ATP per glucose: 1,3BPG → 3-PG
- 2 ATP per glucose: PEP → Pyruvate
After glyceraldehyde 3-phosphate (GA3P) is formed, what is the next compound formed in glycolysis?
Step 5 (payoff): GA3P forms 1,3-bisphosphoglycerate (1,3BPG).
This yields 2 NADH per glucose (1 per GA3P).
After 3-phosphoglycerate (3-PG) is formed, what is the next compound formed in glycolysis?
Step 7: 3-PG is converted to 2-phosphoglycerate (2-PG).
After 2-phosphoglyerate (2-PG) is formed, what is the next compound formed in glycolysis?
Step 8 (payoff): 2-PG becomes phosphoenolpyruvate (PEP).
Which enzyme converts phosphoenolpyruvate to pyruvate?
Step 9 (payoff): PEP is converted to pyruvate by pyruvate kinase.
This yields 2 ATP per glucose (1 per PEP).
In which organs is glucokinase expressed?
Glucokinase is a high-capacity isoenzyme of hexokinase expressed in the liver and pancreas. It is induced by insulin and is a key component of insulin's hypoglycemic effect.
In skeletal muscle, which enzyme sequesters glucose within the cell?
A) Phosphoglucose isomerase
To sequester glucose within a cell, it must be phosphorylated to make glucose-6-phosphate. G6P can’t leave the cell without being dephosphorylated.
- In skeletal muscle, hexokinase performs this phosphorylation.
- In the liver, brain, and pancreas, glucokinase performs this function.
What is the rate-limiting step of glycolysis?
The formation of F1,6BP by PFK-1 is irreversible and rate-limiting.
What enzyme catalyzes the first step of glycolysis, in which glucose is converted to glucose-6-phosphate (G6P)?
Step 1 (preparatory): Hexokinase converts glucose to glucose-6-phosphate (G6P). This sequesters glucose in the cell, as only unphosphorylated glucose can exit the cell. G6P formation also effectively decreases intracellular glucose, driving more glucose into the cell.
How does low blood glucose cause fructose-2,6-bisphosphatase activity to predominate over phosphofructokinase-2 in glycolysis?
Phosphofructokinase-2 / fructose-2,6-bisphosphatase is a bifunctional enzyme regulating phosphofructokinase-1. F26BPase is favored under the following pathway:
- Low blood glucose elevates glucagon secretion
- Glucagon secretion causes phosphorylation of PFK-2 via cAMP pathway
- F2,6BPase activity now predominate
- F26BPase synthesizes fructose-6-phosphate from fructose-2,6-bisphosphonate
- Lower concentrations of F26BP decreases the activity of PFK-1
Which 2 molecules allosterically inhibit pyruvate kinase?
Pyruvate kinase is allosterically inhibited by ATP and alanine.
How does fructose-6-phosphate inhibit glucokinase?
Glucokinase is further regulated by fructose-6-phosphate. F6P binds to the same receptor as glucokinase regulatory protein (GKRP), thereby enhancing GKRP's ability to inhibit glucokinase.
What is the difference in the regulation of hexokinase and glucokinase by glucose-6-phosphate?
Hexokinase and glucokinase are regulated by various means. For instance, hexokinase is inhibited by glucose-6-phosphate, whereas glucokinase is not inhibited by G6P. The regulation of hexokinase by G6P prevents overconsumption of ATP during its reaction.
Which three compounds decrease the activity of phosphofructokinase-1?
Phosphofructokinase-1 activity is decreased by elevated concentrations of:
How do low levels of glucose affect liver pyruvate kinase activity?
Pyruvate kinase may also be inhibited by low blood glucose levels, allowing for PEP to enter gluconeogenesis via the following pathway:
- Low glucose levels detected
- Increased glucagon secretion
- Increased cAMP and protein kinase A activity
- Phosphorylation leads to inactivation of pyruvate kinase
Which 2 molecules activate pyruvate kinase?
Pyruvate kinase activity is increased by fructose 1,6-bisphosphate (F1,6BP) and phosphoenolpyruvate (PEP).
Which two substrates increase the activity of phosphofructokinase-1?
Phosphofructokinase-1 activity is increased in the presence of AMP and fructose-2,6-bisphosphate.
How does high blood glucose cause phosphofructokinase-2 to predominate over fructose-2,6-bisphosphatase?
Phosphofructokinase-2 (PFK2) / fructose-2,6-bisphosphatase (F26BPase) is a bifunctional enzyme regulating phosphofructokinase-1. PFK2 is favored under the following pathway:
- High blood glucose causes insulin secretion
- Insulin activates protein phosphatase
- Protein phosphatase dephosphorylates PFK2
- PFK2 then predominates over F26BPase
- PFK2 synthesizes fructose-2,6-bisphosphate from fructose-6-phosphate
- F26BP is a potent activator of PFK-1
Does hexokinase have a high or low affinity (Km) and capacity (Vmax) to glucose?
Hexokinase has a high affinity (decreased Km) and a low capacity (decreased Vmax) for glucose. The high affinity allows for glycolysis to occur, depsite low blood glucose levels.
What are the four key regulatory enzymes of glycolysis?
Glycolysis is regulated by four key enzymes:
- Hexokinase (most tissues except liver and beta-cells of the pancreas)
- Glucokinase (liver and beta-cells of the pancreas)
- Pyruvate kinase
Which enzyme's genetic mutation may result in maturity-onset diabetes of the young?
Glucokinase genetic mutations on chromosome 7 may result in maturity-onset diabetes of the young (MODY). Glucokinase, within the beta-cells of the pancreas, acts as a glucose sensor, thus when a mutation is present, impaired glucose sensation occurs leading to persistant hyperglycemia and impaired insulin secretion.
Does glucokinase have a high or low affinity (Km) and capacity (Vmax) to glucose?
Glucokinase has a low affinity (increased Km) and a high capacity (increased Vmax) for glucose.
Remember, GLUcokinase is a GLUtton with an insatiable Vmax.
How does hexokinase and glucokinase respond to insulin secretion?
Hexokinase is not triggered by insulin, whereas glucokinase is triggered by insulin.
Phosphofructokinase-1 is a key glycolytic enzyme. Which molecule has the greatest upregulating effect on this enzyme?
A) Adenine triphosphate
B) Guanosine triphosphate
D) Guanosine monophosphate
PFK-1 activity is ↑ by AMP and F2,6BP. F2,6BP is produced by PFK-2.
The oxidation of acetyl-CoA by the TCA cycle will account for how many additional molecules of ATP per glucose molecule?
The oxidation of acetyl-CoA by the TCA cycle will account for additional 36 molecules of ATP per glucose molecule.
What is the primary purpose of the metabolic reaction involving lactate dehydrogenase?
The primary purpose of anaerobic glycolysis is to regenerate NAD+.
What does the glycerol-3-phosphate shuttle do and why is it necessary?
In anaerobic conditions NAD+ must be “regenerated” for glycolysis to continue. Since NADH cannot cross mitochondrial membrane, the reducing equivalents from the NADH formed in glycolysis are taken up into mitochondria for oxidation by shuttle mechanism.
What do you need to know about 2-3BPG and erythrocytes?
2-3BPG binds to Hb, decreasing its affinity for O2.
What do you need to know about fructose metabolism and diabetic patients?
In liver, kidney and intestine, fructokinase phosphorylates fructose to fructose-1-phosphate.
Not affected by Insulin – diabetic patients can clear fructose.
What is galactosemia the result of?
Galactosemia is the result of a lack of galactose-1-phosphate uridyltransferase.
What pathway do fructose, galactose, and mannose for metabolism?
Fructose, galactose and mannose enters the glycolytic pathway for metabolism.
What does galactose enter the glycolytic pathway as?
Galactose will enter the glycolytic pathway as glucose-6-phosphate.
What does fructose enter the glycolytic pathway as?
Fructose enters the glygolytic pathway as glyceraldehyde-3-phosphate.
What are the fates of pyruvate produced by glycolysis?