HMP Shunt Overview and Functions

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Questions and Answers

What is the primary storage form of carbohydrates in animals?

Fructose

Starch

Glycogen (correct)

Glucose

Which glucosidic bond types are present in glycogen structure?

α1-4 and β1-6 bonds

α1-4 and α1-6 bonds (correct)

β1-4 and α1-3 bonds

β1-4 and β1-6 bonds

What triggers glycogenolysis in the liver?

Epinephrine

Cortisol

Insulin

Glucagon (correct)

What is the primary function of the HMP shunt?

Production of NADPH+H+ and pentoses Signup and view all the answers

Which enzyme is responsible for forming UDP-glucose in liver cells?

Glucokinase Signup and view all the answers

What is the role of glycogenin in the synthesis of glycogen?

It acts as a glycogen primer. Signup and view all the answers

Which phase of the HMP shunt is irreversible?

Oxidative phase Signup and view all the answers

During prolonged fasting, how long does liver glycogen typically last?

12-18 hours Signup and view all the answers

What stimulates glucose-6-phosphate dehydrogenase, the key enzyme in HMP shunt?

Insulin and NADP+ Signup and view all the answers

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

2 glucose-6-P and 1 glyceraldehyde-3-P Signup and view all the answers

What is the main source of glucose for muscle glycogen synthesis?

Blood glucose Signup and view all the answers

Which compound does reduced glutathione remove to maintain RBC integrity?

Hydrogen peroxide Signup and view all the answers

Which non-carbohydrate sources can contribute to liver glycogen synthesis?

Lactate and glycerol Signup and view all the answers

Which substance is produced from glucose in the uronic acid pathway?

Glucuronic acid Signup and view all the answers

What is a key product derived from UDP-glucuronic acid?

Glycosaminoglycans Signup and view all the answers

In which part of the cell does the HMP shunt take place?

Cytoplasm Signup and view all the answers

What type of bond does glycogen synthase primarily form during glycogenesis?

α 1-4 glycosidic bond Signup and view all the answers

Which enzyme is responsible for the breakdown of α 1-4 glycosidic bonds during glycogenolysis?

Phosphorylase Signup and view all the answers

What happens to glucose-6-phosphate in muscle cells after glycogenolysis?

It accumulates as it cannot leave the muscle. Signup and view all the answers

During glycogenesis, how many glucose units can glycogen synthase elongate the primer by?

Up to 11 glucose units Signup and view all the answers

Which enzyme removes the last glucose unit attached by an α 1-6 linkage during glycogenolysis?

Debranching enzyme Signup and view all the answers

What is the primary outcome of glucan transferase activity during glycogenolysis?

Transfer of glucose units to neighboring chains Signup and view all the answers

What regulates the activity of glycogen synthase?

Phosphorylation state Signup and view all the answers

In the liver, what enzyme converts glucose-6-phosphate to glucose?

Glucose-6-phosphatase 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 used.
Location: Cytoplasm of many tissues.
Phases: Occurs in two phases.
- Oxidative (irreversible): 3 glucose molecules are converted to 3 ribulose-5-P, producing NADPH+H+ and CO2.
- Non-oxidative (reversible): 3 ribulose-5-P are converted to 2 glucose-6-P and 1 glyceraldehyde-3-P.

Functions of HMP Shunt

Production of pentoses (ribose-5-P): crucial for DNA, RNA, NAD, FAD, ATP, and GTP synthesis.
Production of NADPH+H+: Essential for fatty acid and steroid hormone synthesis, non-essential amino acid synthesis, converting pyruvate to malate via malic enzyme, and reduced glutathione synthesis in erythrocytes.

Glutathione Reductase and Reduced Glutathione

Reduced glutathione is needed for cellular hydrogen peroxide removal (maintaining cell membrane integrity in RBCs).
The enzyme glutathione peroxidase converts hydrogen peroxide to water, while the enzyme glutathione reductase regenerates reduced glutathione.

Regulation of HMP Shunt

Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme.
Stimulated by insulin and NADP+.
Inhibited by NADPH+H+ and acetyl CoA.

Uronic Acid Pathway

Definition: An alternative pathway for glucose oxidation producing glucuronic acid.
- Location: Cytoplasm of many tissues.
Importance:
- Production of UDP-glucuronic acid, a precursor for
- Synthesis of glycosaminoglycans (GAGs).
- Synthesis of vitamin C (L-ascorbic acid) in animals (not humans – humans lack L-gluconolactone oxidase)
- Conjugation reactions: Making substances like bilirubin more water-soluble for excretion.
- Detoxification reactions: Making toxic compounds less toxic.
- Production of pentoses (ribose-5-P).

Glycogen Metabolism

Definition: Glycogen is the storage form of carbohydrates in animals, composed of α-D glucose units linked by α1-4 glucosidic bonds and α1-6 glucosidic bonds at branch points.
Storage Location: Liver and muscles.

Liver Glycogen

Percentage: Up to 6% of liver mass.
Function: Maintaining blood glucose levels during fasting.
Depletion: Depletes after 12-18 hours of fasting.
Regulation: Glucagon stimulates glycogenolysis (breakdown).

Muscle Glycogen

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

Glycogenesis

Definition: Synthesis of glycogen from glucose.
Location: Cytoplasm of liver and muscle cells.
Sources for liver glycogen:
- Blood glucose
- Other hexoses (galactose and fructose)
- Non-carbohydrate sources (e.g., lactate and glycerol via gluconeogenesis).
Sources for muscle glycogen: Blood glucose only.
Steps: Several enzymatic steps, including formation of UDP-glucose, the use of a glycogen primer (often a protein glycogenin), and elongation to 11 glucose units using glycogen synthase; lastly branching by branching enzyme.

Glycogenolysis

Definition: Breakdown of glycogen into glucose or glucose-6-P.
Location: Cytoplasm of liver and muscle cells.
Steps:
- Phosphorylase enzyme: Breaks down α1-4 glycosidic bonds by phosphorylysis (adding phosphate).
- Debranching enzyme: Removes α1-6 branch points.
- Glucan transferase enzyme: transfers three glucose residues to adjacent chain to shorten branch point, leaving one glucose attached at α1-6 branch point.

Fate of Glucose-6-Phosphate

Liver: Contains glucose-6-phosphatase for converting glucose-6-phosphate to glucose for release into the blood.
Muscle: Lacks glucose-6-phosphatase, so glucose-6-phosphate remains in the muscle during glycogenolysis.

Regulation of Glycogenesis and Glycogenolysis

Coordinated regulation: Conditions stimulating one process inhibit the other.
Key enzymes:
- Glycogen synthase: Active (dephosphorylated) form vs. inactive (phosphorylated) form.
- Phosphorylase: Active (phosphorylated) form vs. inactive (dephosphorylated) form.

Regulation During Fasting

Blood glucose decrease stimulates epinephrine release in muscles and glucagon in the liver.
These hormones activate adenylate cyclase, producing cAMP.
cAMP activates protein kinase which phosphorylates and inactivates glycogen synthase, and phosphorylates and activates phosphorylase, inhibiting glycogen synthesis and activating glycogenolysis.

Regulation After Meals

Increased blood glucose stimulates insulin release.
Insulin stimulates glycogen synthesis.
Insulin inhibits glycogen breakdown.
This process occurs via phosphodiesterase, breaking down cAMP to 5AMP, halting glycogen degradation and stimulating phosphatase activity which removes phosphate groups from enzymes for deactivation.

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Description

Explore the Hexose Monophosphate Shunt (HMP Shunt), an alternative glucose oxidation pathway. Understand its phases, the production of vital biomolecules, and the role of reduced glutathione in cellular health. This quiz covers the biochemical processes and their significance in various tissues.