MN08 - Glycolysis and Gluconeogenesis

How does glucose enter cells via GLUT transporters?

Glucose enters cells via GLUT transporters through facilitated diffusion, which is sodium-independent and tissue-specific.

How does glucose enter intestinal and renal epithelial cells via SGLT transporters?

Glucose enters epithelial cells of the intestine and renal tubules via SGLT transporters through sodium-dependent secondary active co-transport.

In which cellular compartment does glycolysis occur?

Glycolysis occurs in the cytosol of all cells.

What is the primary function of glycolysis in cellular metabolism?

Glycolysis is the principal pathway for glucose oxidation to generate ATP and metabolic intermediates.

What are the two stages of glycolysis and what occurs in each stage?

Glycolysis consists of an energy investment stage (reactions 1-5, ATP is consumed) and an energy generation stage (reactions 6-10, ATP is produced).

What is the role of glucose phosphorylation in glycolysis?

Glucose phosphorylation produces glucose-6-phosphate and traps glucose inside the cell.

Which enzymes catalyze the phosphorylation of glucose to glucose-6-phosphate in glycolysis?

Hexokinase and glucokinase catalyze the phosphorylation of glucose.

Is the phosphorylation of glucose to glucose-6-phosphate reversible and how much ATP is used?

The reaction is irreversible and uses 1 ATP.

Which enzyme catalyzes the rate-limiting step of glycolysis and what reaction does it perform?

Phosphofructokinase-1 (PFK-1) catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate.

Is the phosphofructokinase-1 (PFK-1) reaction reversible and what is its energy requirement?

The reaction is irreversible and requires 1 ATP.

Which molecules inhibit phosphofructokinase-1 (PFK-1) and what do they indicate?

ATP and citrate inhibit PFK-1, indicating high cellular energy levels.

Which molecules activate phosphofructokinase-1 (PFK-1) and what do they indicate?

AMP and ADP activate PFK-1, indicating low cellular energy levels.

What molecule activates phosphofructokinase-1 (PFK-1) and how is it produced?

Fructose-2,6-bisphosphate activates PFK-1 and is produced by phosphofructokinase-2 (PFK-2).

What controls the activity of phosphofructokinase-2 (PFK-2) in glycolysis regulation?

The insulin-to-glucagon ratio controls PFK-2 activity.

Which enzyme cleaves fructose-1,6-bisphosphate in glycolysis and what are the products?

Aldolase A cleaves fructose-1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP).

What happens to dihydroxyacetone phosphate (DHAP) during glycolysis?

Dihydroxyacetone phosphate is converted into glyceraldehyde-3-phosphate during glycolysis.

Which enzyme catalyzes the oxidation of glyceraldehyde-3-phosphate (GAP) in glycolysis?

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes this reaction.

What molecule is required as a coenzyme for glyceraldehyde-3-phosphate dehydrogenase (GAPDH)?

NAD+ is required as the coenzyme for glyceraldehyde-3-phosphate dehydrogenase.

What product is formed during oxidation of glyceraldehyde-3-phosphate (GAP)?

1,3-bisphosphoglycerate (1,3-BPG) is produced during oxidation of glyceraldehyde-3-phosphate.

What is substrate-level phosphorylation in glycolysis?

Substrate-level phosphorylation is the direct transfer of a phosphate group to ADP to form ATP during glycolysis.

Which enzyme catalyzes ATP production from 1,3-bisphosphoglycerate in glycolysis?

Phosphoglycerate kinase catalyzes ATP formation from 1,3-bisphosphoglycerate.

Which enzyme catalyzes ATP production during conversion of phosphoenolpyruvate (PEP) to pyruvate?

Pyruvate kinase catalyzes ATP formation during conversion of phosphoenolpyruvate to pyruvate.

What is the net ATP yield produced per glucose molecule during glycolysis?

Glycolysis produces a net gain of 2 ATP per glucose molecule.

What is the final product of glycolysis and is its formation reversible?

The final product of glycolysis is pyruvate, and its formation is irreversible.

What molecule activates pyruvate kinase in glycolysis and what type of regulation is this?

Fructose-1,6-bisphosphate activates pyruvate kinase via feedforward regulation.

How does phosphorylation affect pyruvate kinase activity?

Phosphorylation by cAMP-dependent protein kinase A inactivates pyruvate kinase.

Under what hormonal conditions is pyruvate kinase inactivated?

Pyruvate kinase is inactivated during low blood glucose when glucagon levels are high.

How does insulin affect glycolysis enzyme levels?

Insulin increases gene expression of glycolytic enzymes, promoting glucose conversion to pyruvate.

What are the three possible metabolic fates of pyruvate?

Pyruvate can be converted to lactate, acetyl-CoA, or ethanol in yeast.

What is lactic acid fermentation and when does it occur?

Lactic acid fermentation is the reduction of pyruvate to lactate under anaerobic conditions or limited oxidative capacity.

In which cellular compartment does lactate formation occur?

Lactate formation occurs in the cytosol.

Which tissues commonly produce lactate under normal or stressed conditions?

Red blood cells, lens, cornea, and skeletal muscle during intense exercise produce lactate.

Which enzyme catalyzes the conversion of pyruvate to lactate and what cofactor is required?

Lactate dehydrogenase catalyzes the conversion of pyruvate to lactate and requires NADH.

Where does oxidative decarboxylation of pyruvate occur and what enzyme catalyzes it?

Oxidative decarboxylation of pyruvate occurs in the mitochondria and is catalyzed by the pyruvate dehydrogenase complex.

What are the products of pyruvate conversion to acetyl-CoA?

The conversion of pyruvate to acetyl-CoA produces acetyl-CoA and NADH.

Is the conversion of pyruvate to acetyl-CoA reversible?

The conversion of pyruvate to acetyl-CoA is irreversible.

Which molecules activate the pyruvate dehydrogenase complex (PDHC)?

ADP, pyruvate, and Ca2+ activate the pyruvate dehydrogenase complex.

Which molecules inhibit the pyruvate dehydrogenase complex (PDHC)?

ATP, NADH, and acetyl-CoA inhibit the pyruvate dehydrogenase complex.

How does phosphorylation affect the pyruvate dehydrogenase complex (PDHC)?

Phosphorylation inactivates the pyruvate dehydrogenase complex, while dephosphorylation activates it.

What is the Cori cycle in carbohydrate metabolism?

The Cori cycle involves lactate produced in muscle or red blood cells being transported to the liver, converted to pyruvate, then to glucose, and released back into the bloodstream.

What is gluconeogenesis and when does it occur?

Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors and occurs during fasting when glycogen stores are depleted.

Which tissues require a continuous supply of glucose supplied by gluconeogenesis?

The brain, red blood cells, lens, cornea, and exercising muscle require continuous glucose.

In which organs and cellular compartments does gluconeogenesis occur?

Gluconeogenesis occurs mainly in the liver and kidney, in both the cytosol and mitochondria.

What are the main substrates used for gluconeogenesis?

The main substrates for gluconeogenesis are glycerol, glucogenic amino acids such as alanine, and lactate.

Why is gluconeogenesis not simply the reverse of glycolysis?

Gluconeogenesis is not a direct reversal because it bypasses the three irreversible glycolytic reactions with alternative enzymes.

Why do glycolysis and gluconeogenesis not occur simultaneously?

Glycolysis and gluconeogenesis do not occur simultaneously because they are tightly regulated by the insulin-to-glucagon ratio.

What enzyme converts pyruvate to oxaloacetate in gluconeogenesis and what coenzyme is required?

Pyruvate carboxylase converts pyruvate to oxaloacetate and requires biotin as a coenzyme.

What molecule activates pyruvate carboxylase?

Acetyl-CoA activates pyruvate carboxylase.

What enzyme converts oxaloacetate to phosphoenolpyruvate (PEP) and what energy molecule is used?

Phosphoenolpyruvate carboxykinase converts oxaloacetate to phosphoenolpyruvate using GTP.

What is the rate-limiting enzyme of gluconeogenesis and what inhibits it?

Fructose-1,6-bisphosphatase is the rate-limiting enzyme of gluconeogenesis and is inhibited by AMP and fructose-2,6-bisphosphate.

What enzyme converts glucose-6-phosphate to free glucose and where is it expressed?

Glucose-6-phosphatase converts glucose-6-phosphate to glucose and is expressed only in the liver and kidney.

How is oxaloacetate transported from the mitochondria to the cytosol during gluconeogenesis?

Oxaloacetate is converted to malate, transported to the cytosol, and then reconverted to oxaloacetate.

How many high-energy phosphate molecules are required to produce one glucose molecule in gluconeogenesis?

Six high-energy phosphate bonds are required, including four ATP and two GTP.

What hormone primarily stimulates gluconeogenesis?

Glucagon primarily stimulates gluconeogenesis.

How does glucagon regulate fructose-2,6-bisphosphate levels and gluconeogenesis?

Glucagon decreases fructose-2,6-bisphosphate levels, which activates gluconeogenesis and inhibits glycolysis.

How does glucagon affect pyruvate kinase activity?

Glucagon causes phosphorylation and inactivation of pyruvate kinase.

Which enzyme expression is increased by glucagon to promote gluconeogenesis?

Glucagon increases expression of phosphoenolpyruvate carboxykinase.