Glycolysis

Which enzymes phosphorylate glucose to glucose-6-phosphate (G6P) in hepatocytes and pancreatic β-cells versus other cells?

Glucokinase in hepatocytes and β-cells; Hexokinase in all other cells

What are the three primary fates of glucose-6-phosphate (G6P)?

Glycolysis

What are the main products of glycolysis from one glucose molecule?

2 net ATP

Where does pyruvate enter after glycolysis in aerobic cells?

The mitochondria (except in red blood cells)

What are the key products of the Hexose Monophosphate Pathway?

NADPH and ribose-5-phosphate

What are four important cellular roles of NADPH produced by the Hexose Monophosphate Pathway?

Reducing oxidative stress

In which tissues does glycogenesis primarily occur?

Hepatocytes (liver cells) and myocytes of skeletal muscle

What is the functional difference between glycogen stored in skeletal muscle versus liver?

Skeletal muscle glycogen is used exclusively for muscle contraction; liver glycogen maintains blood glucose during fasting

How many net ATP molecules are produced from glycolysis per glucose?

2 net ATP

What happens at reaction 5 in glycolysis that leads to doubling of ATP

NADH

Which enzyme catalyzes the irreversible phosphorylation of glucose to G6P?

Hexokinase or glucokinase

How is hexokinase regulated?

It is allosterically inhibited by G6P (feedback inhibition)

How is glucokinase regulation different from hexokinase?

Glucokinase is not inhibited by G6P and has no restriction on glucose processing rate

Which enzyme catalyzes the phosphorylation of fructose-6-phosphate (F6P) to fructose-1

6-bisphosphate (F-1

What are the allosteric activators and inhibitors of PFK-1?

Activators: AMP and F-2

How does the insulin:glucagon ratio regulate PFK-1 activity?

It dictates the concentration of fructose-2

Which enzyme catalyzes the substrate-level phosphorylation that forms ATP from 1

3-bisphosphoglycerate?

What type of reaction does enolase catalyze?

Dehydration of 2-phosphoglycerate to phosphoenolpyruvate (PEP)

How is pyruvate kinase regulated in the liver during fed and fasting states?

It is activated (dephosphorylated) in the well-fed state and inhibited (phosphorylated) in the fasting state

What enzyme reduces pyruvate to lactate under anaerobic conditions?

Lactate dehydrogenase (LDH)

Why is lactate production necessary in red blood cells?

Because they lack mitochondria and rely on anaerobic glycolysis for ATP production

Oxidation of G3P to 1 3-BPG involves glyceraldehyde-3-phosphate NAD+ and Pi being converted to 1 3-bisphosphoglycerate and NADH catalyzed by glyceraldehyde-3-phosphate dehydrogenase

It is a reversible reaction absolutely dependent on NAD+ as cofactor

How many equivalents of G3P are processed in glycolysis after isomerization from DHAP

Two equivalents of G3P are processed

What functional group change occurs to G3P during its oxidation to 1 3-BPG

The aldehyde group of G3P is oxidized to a carboxylic acid forming 1 3-BPG with a high energy acid anhydride bond

Substrate-level phosphorylation of 1 3-BPG to 3PG and ATP is catalyzed by which enzyme

Phosphoglycerate kinase

Is the phosphorylation of ADP to ATP by phosphoglycerate kinase reversible or irreversible

It is a reversible reaction and the only reversible kinase enzyme in glycolysis

How many ATP molecules are produced per glucose molecule in the 1 3-BPG to 3PG step

Two ATP are produced because two equivalents of 1 3-BPG are processed

What is the source of energy for ATP formation during the phosphoglycerate kinase reaction

The high free energy acid anhydride bond at C-1 of 1 3-BPG

What enzyme converts 1 3-BPG to 2 3-BPG in erythrocytes

Bisphosphoglycerate mutase

Is the conversion of 1 3-BPG to 2 3-BPG reversible

No it is not reversible and the high energy bond at C-1 is lost

What is the physiological role of 2 3-BPG in red blood cells

2 3-BPG binds hemoglobin to stabilize the T state and facilitates oxygen release by shifting the O2 dissociation curve to the right

How does fetal hemoglobin HbF differ in affinity for 2 3-BPG compared to adult hemoglobin HbA

HbF has weaker affinity for 2 3-BPG than HbA

What happens to 2 3-BPG eventually in erythrocytes

It is hydrolyzed by a phosphatase to form 3PG without ATP production

Which enzyme catalyzes the isomerization of 3-phosphoglycerate to 2-phosphoglycerate

Phosphoglycerate mutase

Is the isomerization of 3PG to 2PG reversible

Yes it is a reversible reaction

What enzyme catalyzes the dehydration of 2-phosphoglycerate to phosphoenolpyruvate PEP

Enolase

Is the conversion of 2PG to PEP reversible

Yes it is reversible

What chemical changes occur during dehydration of 2PG to PEP

Removal of H2O forms a double bond between C-2 and C-3 and creates a high energy phosphorylated enol structure

What enzyme catalyzes substrate-level phosphorylation converting PEP to pyruvate and ATP

Pyruvate kinase

Is the pyruvate kinase reaction reversible

No it is irreversible

How is pyruvate kinase regulated in the liver

It is inhibited by phosphorylation during fasting and activated by dephosphorylation in the well-fed state

What is the fate of pyruvate under anaerobic conditions

Pyruvate is reduced to lactate by lactate dehydrogenase

What cofactor is regenerated by lactate dehydrogenase to maintain glycolysis

NAD+

Which cells rely exclusively on anaerobic glycolysis and produce lactate continuously

Erythrocytes

Why are different LDH isozymes clinically important

Their presence in blood indicates tissue-specific infarctions such as heart liver or skeletal muscle damage

What happens to glycolysis in skeletal muscle during the well-fed state

Glycolysis is significantly inhibited but not stopped and glycogenesis is strongly activated

How does the liver respond to a high insulin to glucagon ratio in the well-fed state

Liver processes carbohydrates producing fatty acids TAGs cholesterol and VLDLs

What is the primary fuel source for the liver during early fasting

The liver uses beta-oxidation of fatty acids for energy during early fasting

How does the liver maintain blood glucose during early fasting

By activating glycogenolysis to release glucose and gluconeogenesis from lactate glycerol and amino acid derivatives

What fuel sources does skeletal muscle prefer during early fasting

Skeletal muscle consumes fatty acids primarily and uses glycogen for contraction glucose uptake is reduced

How is muscle protein catabolism related to gluconeogenesis

Muscle protein is catabolized releasing amino acids which are deaminated and sent to the liver for gluconeogenesis

What nitrogen-containing amino acids shuttle nitrogen from muscle to liver

Alanine and glutamine

How does adipose tissue generate energy during fasting

Adipose tissue uses beta-oxidation of fatty acids and consumes ketone bodies as fasting progresses

What are the three main fates of glucose-6-phosphate G6P in the cell

Glycolysis Pentose Phosphate Pathway and Glycogenesis

Which enzymes phosphorylate glucose in hepatocytes and other cells

Glucokinase in hepatocytes and beta-cells Hexokinase in all other cells

What are the key products of the Pentose Phosphate Pathway

NADPH and ribose-5-phosphate

What is NADPH used for in cells

Reducing oxidative stress supporting biosynthesis producing nitric oxide and aiding phagocyte respiratory burst

Where is glycogen synthesized and stored in the body

In hepatocytes of the liver and myocytes of skeletal muscle

What is the role of glycogen in skeletal muscle

It serves as a glucose reserve for muscle contraction and energy

How does the liver use glycogen during fasting

The liver breaks down glycogen to maintain blood glucose levels

Which enzyme catalyzes the phosphorylation of fructose-6-phosphate to fructose-1

6-bisphosphate

What allosteric activators regulate PFK-1

AMP and fructose-2

What allosteric inhibitors regulate PFK-1

ATP and citrate

How does the insulin to glucagon ratio affect PFK-1 activity

High insulin increases fructose-2

What enzyme catalyzes the phosphorylation of glucose to glucose-6-phosphate in most cells

Hexokinase

How does glucokinase differ from hexokinase in regulation

Glucokinase is not inhibited by G6P allowing liver to process large amounts of glucose

What is the significance of fructose-2

6-bisphosphate in glycolysis

How is pyruvate kinase regulated in the liver during fasting and feeding

Inhibited by phosphorylation during fasting and activated when dephosphorylated in the fed state

What happens to lactate produced in anaerobic glycolysis

It is transported to the liver and converted back to glucose via the Cori cycle

What is the Cori cycle

The process of lactate produced by anaerobic glycolysis in muscle being transported to the liver and converted to glucose

How is glycogenolysis regulated differently in liver and skeletal muscle

Liver is regulated by glucagon and epinephrine skeletal muscle mainly by epinephrine AMP and Ca2+

Why can skeletal muscle not contribute glucose to the blood

It lacks glucose-6-phosphatase and only produces G6P for its own use

What is the fate of pyruvate in aerobic conditions

It is converted to acetyl-CoA by the pyruvate dehydrogenase complex entering the TCA cycle

What cofactors are required by the pyruvate dehydrogenase complex

Thiamine pyrophosphate lipoic acid Coenzyme A FAD NAD+

How does acetyl-CoA regulate pyruvate dehydrogenase activity

High acetyl-CoA inhibits PDH and activates pyruvate carboxylase for gluconeogenesis