HMP Shunt Overview and Functions

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.

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.