HMP Shunt Overview and Functions

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Questions and Answers

What is the primary role of liver glycogen?

Detoxifying harmful substances

Increasing muscle mass

Maintaining blood glucose during fasting (correct)

Acting as a source of energy during intense exercise

Which of the following is NOT a source of glucose for liver glycogen synthesis?

Fructose

Blood glucose

Galactose

Free fatty acids (correct)

What enzyme is involved in the conversion of glucose to glucose-6-P in muscle cells?

Phosphofructokinase

Glucokinase

Glycogen synthase

Hexokinase (correct)

What happens to the glycogen stored in muscles after prolonged vigorous exercise?

It completely depletes Signup and view all the answers

What is the function of glucagon in glycogen metabolism?

Stimulating glycogenolysis Signup and view all the answers

Which bond types are indicative of the structure of glycogen?

α1-4 and α1-6 glucosidic bonds Signup and view all the answers

What is the initial step in glycogenesis involving glucose?

Formation of UDP-glucose Signup and view all the answers

Which component is required for the formation of glycogen from UDP-glucose units?

Glycogen primer Signup and view all the answers

What is a primary function of the HMP shunt?

Production of pentoses for nucleic acids Signup and view all the answers

Which enzyme is critical in the regulation of the HMP shunt?

Glucose-6-phosphate dehydrogenase Signup and view all the answers

In the oxidative phase of the HMP shunt, what is produced along with ribulose-5-P?

NADPH+H+ Signup and view all the answers

What is the end product from the non-oxidative phase of the HMP shunt?

Glyceraldehyde-3-P and glucose-6-P Signup and view all the answers

What does the uronic acid pathway primarily convert glucose into?

Glucuronic acid Signup and view all the answers

What is the importance of UDP-glucuronic acid produced in the uronic acid pathway?

For synthesis of glycosaminoglycans Signup and view all the answers

Which substance inhibits glucose-6-phosphate dehydrogenase activity in the HMP shunt?

NADPH+H+ Signup and view all the answers

Which of the following compounds can be produced from NADPH+H+ through the HMP shunt?

Non-essential amino acids Signup and view all the answers

What is the primary function of glycogen synthase in glycogenesis?

It catalyzes the formation of α 1-4 glucosidic bonds. Signup and view all the answers

Which enzyme is responsible for breaking down glycogen into glucose-1-phosphate during glycogenolysis?

Phosphorylase enzyme Signup and view all the answers

What occurs during the action of the branching enzyme?

It transfers glucose units to form a branch point. Signup and view all the answers

What happens to glucose-6-phosphate in the liver?

It is converted to glucose and released into the blood. Signup and view all the answers

Which form of glycogen synthase is considered the active form?

Glycogen synthase a Signup and view all the answers

During which condition is glycogenesis stimulated?

After carbohydrate-rich meals Signup and view all the answers

What is the role of the debranching enzyme in glycogenolysis?

It removes glucose units attached by α 1-6 linkage. Signup and view all the answers

What is a consequence of the lack of glucose-6-phosphatase in muscle cells?

Muscle glycogenolysis ends with glucose-6-phosphate, which cannot leave the muscle. Signup and view all the answers

Study Notes

HMP Shunt (Hexose Monophosphate Shunt)

Definition: An alternative pathway of glucose oxidation where ATP is neither produced nor utilized.
Location: Cytoplasm of many tissues
Phases: The reactions occur in two phases:
- Oxidative phase: Three glucose molecules are converted into three ribulose-5-phosphates, producing NADPH+H+ and CO2.
- Non-oxidative phase: Three ribulose-5-phosphates are converted into two glucose-6-phosphates and one glyceraldehyde-3-phosphate. This phase is reversible.

Functions of HMP Shunt

Pentose Production: Provides ribose-5-phosphate for the synthesis of DNA, RNA, ATP, GTP, and other molecules.
NADPH Production: Crucial for fatty acid and steroid hormone synthesis, non-essential amino acid synthesis, malate production from pyruvate, and reduced glutathione synthesis in erythrocytes.

Glutathione Reductase

Critical for reducing oxidized glutathione (G-S-S-G) to reduced glutathione (2 G-SH). This reduced form is needed to maintain normal erythrocyte function via the detoxification of H₂O₂.

Regulation of HMP Shunt

Key Enzyme: Glucose-6-phosphate dehydrogenase (G6PD)
Stimulation: Insulin and NADP+
Inhibition: NADPH+H+ and acetyl CoA

Uronic Acid Pathway

Definition: An alternative pathway for glucose oxidation converting glucose into glucuronic acid.
Location: Cytoplasm of many tissues
Importance:
- Substrate Synthesis: Used in the synthesis of glycosaminoglycans.
- Vitamin C Production (Animals Only): Contributes to the synthesis of ascorbic acid (vitamin C) in some animals but not humans. Humans lack the enzyme to convert glucuronic acid to ascorbic acid.

Conjugation/Detoxification

Facilitates the excretion of substances, such as bilirubin, by increasing their water solubility.
Involved in detoxification of toxic compounds, rendering them less toxic and more easily excreted.

Glycogen Metabolism

Definition: Glycogen acts as the primary carbohydrate storage form in animals.
Structure: Formed from α-D glucose units linked via α1-4 glucosidic bonds (linear) and α1-6 glucosidic bonds (branch points).
Storage Locations: Primarily stored in the liver and muscles.

Liver Glycogen

Function: Maintains blood glucose levels during fasting.
Quantity: Constitutes up to 6% of liver mass
Depletion time: Empties in about 12 - 18 hours of fasting.
Regulation: Glucagon stimulates glycogenolysis.

Muscle Glycogen

Function: Acts as a source of glucose-6-phosphate for muscle contraction.
Quantity: Rarely exceeds 1% of muscle mass
Depletion: Depletes after prolonged, vigorous exercise.
Regulation: No effect from glucagon

Glycogenesis

Definition: The synthesis of glycogen from glucose.
Location: Cytoplasm of liver and muscle cells.
Sources for liver glycogen:
- Blood glucose
- Other hexoses (galactose, fructose)
- Non-carbohydrate sources (e.g., lactate, glycerol)
Sources for muscle glycogen:
- Blood glucose
Steps:
1. Formation of UDP-glucose.
2. Formation of glycogen from UDP-glucose units:
  - Glycogen primer formation.
  - Glycogen synthase action (catalyzes the formation of alpha-1,4-glycosidic bonds).
  - Branching enzyme action (catalyzes the formation of alpha-1,6-glycosidic bonds).

Glycogenolysis

Definition: The breakdown of glycogen into glucose.
Location: Cytoplasm of liver and muscle cells.
Steps:
1. Phosphorylase enzyme: Breaks down alpha-1,4-glycosidic bonds by phosphorylysis.
2. Glucan transferase enzyme: Transfers 3 glucose units from one branch to another.
3. Debranching enzyme: Removes the remaining glucose unit linked by alpha-1,6-glycosidic bonds.

Fate of Glucose-6-Phosphate

Liver: Contains glucose-6-phosphatase, converting glucose-6-phosphate into glucose, which is released into the bloodstream.
Muscle: Lacks glucose-6-phosphatase, so glycogenolysis in muscle ends with glucose-6-phosphate, which cannot leave the muscle.

Regulation of Glycogenesis and Glycogenolysis

Coordinated regulation: Conditions triggering glycogenesis inhibit glycogenolysis, and vice-versa.
Key enzymes:
- Glycogen synthase (active form is dephosphorylated, inactive form is phosphorylated).
- Phosphorylase (active form is phosphorylated, inactive form is dephosphorylated).

Regulation During Fasting

Blood glucose decreases.
Release of epinephrine (muscle) and glucagon (liver).
Activation of adenylate cyclase.
cAMP production.
cAMP-dependent protein kinase activation.
Phosphorylation and inactivation of glycogen synthase.
Phosphorylation and activation of phosphorylase.
Glycogenolysis is stimulated.

Regulation After Meals

Blood glucose increases.
Insulin release.
Stimulation of glycogenesis.
Inhibition of glycogenolysis.
Phosphodiesterase activation.
cAMP breakdown.
Phosphatase activation.

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Description

Explore the workings of the Hexose Monophosphate Shunt (HMP Shunt) and its significance in cellular metabolism. This quiz covers the two phases of the shunt, its role in producing essential molecules like NADPH and ribose-5-phosphate, and its importance in various biosynthetic pathways.