Carbohydrates and Glycogen Metabolism Quiz

Carbohydrate Metabolism I

• Carbohydrate digestion and absorption are covered.
• Glycogenolysis and glycogenogenesis, and their regulation, are also discussed.

Glycaemia

• Blood glucose (Glc) level is 3.3-5.8 mmol/L.
• This level is a result of tissue metabolism and hormonal regulation.
• Glycosylated Hb (HbA1c) levels are determined if blood glucose is higher than normal for prolonged periods.

Normal Blood Glucose Levels

• Fasting: 4.4-5.6 mmol/L (80-100 mg/dL)
• 12 hours: 4.4 mmol/L (80 mg/dL)
• 3 days: 3.9 mmol/L (70 mg/dL)
• 5-6 weeks: 3.6 mmol/L (65 mg/dL)

Sources of Blood Glucose

• Blood glucose levels are affected by dietary glucose, glycogenolysis, and gluconeogenesis.
• Dietary glucose leads to a rapid increase in blood glucose.
• Glycogenolysis contributes to maintaining blood glucose during fasting.
• Gluconeogenesis is vital during prolonged fasting to maintain blood glucose levels.

Carbohydrates in Food

• Carbohydrates are the primary energy source for organisms.
• Developed countries typically consume 40% carbohydrates (250-800 g/day).
• The average intake of carbohydrates is approximately 300 g/day.
• Carbohydrates originate primarily from plants (starch) with a smaller contribution from animals (glycogen).
• Lactose is an exception.

Carbohydrates - Clinical Notes

• Gluconeogenesis can be synthesized from amino acids (glucogenic amino acids).
• This synthesis helps with protein-sparing in the body.
• Liver issues can affect nitrogen processing.
• Lipolysis can lead to the production of compounds known as ketone bodies, causing ketoacidosis.
• The Atkinson keto diet is used therapeutically.
• The glycemic index must be considered when substituting glucose with other sugars.
• Fructose has a cautionary note on use.

Saccharides in the Human Diet

• Polysaccharides:
  • Starch (amylose, amylopectin)
  • Glycogen
  • Non-starch polysaccharides (cellulose, pectins)
• Free saccharides:
  • Glucose, fructose, mannose, ribose, deoxyribose
• Disaccharides:
  • Sucrose, lactose, mannose
• Oligosaccharides:
  • Raffinose, fructans
• Saccharidic alcohols:
  • Sorbitol, manitol, gulcitol, inositol

Intake of Saccharides: Digestion, Absorption, and Transport

• Only monosaccharides are absorbed in the intestines.
• Monosaccharides are transported to the liver before being distributed throughout the body.
• Glucose is a vital substrate for metabolic processes.
• Glucose can be used to release energy via glycolysis or for the synthesis of glycogen.
• Glucose can be converted into other saccharides or utilized in the synthesis of other essential compounds (lipids and amino acids).
• Glucose is crucial in the production of glycoproteins, proteoglycans, and glycolipids.

Saccharide Digestion

• Enzymes from salivary glands, pancreas, and intestine are involved in carbohydrate digestion.
• Salivary a-amylase (ptyalin) initiates carbohydrate digestion by hydrolyzing alpha-1,4 glycosidic bonds.
• Pancreatic α-amylase continues the process of starch digestion.
• Products of starch cleavage include maltose, maltotriose, and maltodextrins.

Intestinal Mucosal Cells and Brush Border Membranes

• Specific enzymes, located in brush border membranes, break down disaccharides like sucrose, lactose, and maltose into their component monosaccharides.
• Saccharase, lactase, and maltase are the key enzymes responsible for this digestion.

Clinical Note - Maltodextrins

• Maltodextrins, used as food additives, have a high glycemic index.
• This leads to large insulin releases and potential GIT issues.

Absorption of Monosaccharides

• Monosaccharides are absorbed by active transport (involving Na+) in the intestinal brush border membranes.
• These substances are then released into the bloodstream through passive transport mechanisms.
• Different monosaccharides have varying transport velocities in the body.

GLUT Transport Proteins

• GLUT transporters are proteins responsible for glucose transport across cell membranes.
• Different tissues express various GLUT isoforms.
• GLUT 1, 2, 3 are high-affinity transporters
• GLUT 4, is an insulin-sensitive transporter.
• GLUT 5 specializes in fructose transport.

Non-Digested Carbohydrates

• Cellulose, hemicellulose, inulin, and pectin are non-digestible carbohydrates (fibers).
• These substances are partially metabolized by gut bacteria in processes that produce probiotics and prebiotics.
• Bacterial breakdown of these substances produces substances such as hydrogen, methane, and various organic acids, which are important in preventing some types of cancer.

Hormonal Regulation of Blood Glucose

• High blood glucose levels trigger insulin release (incretins are also involved).
• Low blood glucose prompts the release of hormones like glucagon, epinephrine, and growth hormone.

Incretins

• Incretins are hormones released from the GIT to stimulate insulin secretion based on the level of glucose in the intestine.
• GIP (gastric inhibitory peptide) is among these incretins, along with GLP-1.
• These hormones play a significant role in controlling digestion and sugar metabolism.
• Incretins enhance glucose-dependent insulin secretion and regulate lipid metabolism.

Clinical Note - Incretin Effect

• Oral glucose intake results in a different insulin response compared to intravenous glucose.
• The incretin effect helps achieve euglycemia in diabetics.

Hypoglycemia

• Low blood glucose levels (hypoglycemia) can be life-threatening.
• The body has counter-regulatory hormones (cortisol, epinephrine, norepinephrine, glucagon) to address low glucose levels.

Pathologies of Carbohydrate Digestion and Metabolism

• Lactose intolerance is a condition caused by lactase deficiency.
• Fructose intolerance stems from the lack of an enzyme, leading to fructose buildup.

Glycogen Metabolism

• Glycogen is the primary storage form of glucose in animals.
• Glycogen is stored in the liver and muscle tissues.
• Glycogenolysis is the process of breaking down glycogen to release glucose.
• Glycogenesis is the process of synthesizing glycogen from glucose.
• Glycogen synthesis begins with glucose 6-phosphate to glucose 1-phosphate conversion, followed by formation of UDP-glucose and the elongation and branching of glycogen chains.
• Glycogen breakdown begins with glycogen phosphorylase breaking down α-1,4 glycosidic bonds in the glycogen chain.
• Debranching enzyme cleaves α-1,6 glycosidic bonds.
• Glucose 6-phosphatase in the liver catalyzes the removal of phosphate from glucose 6-phosphate, releasing free glucose into the bloodstream.

Regulation of Glycogen Metabolism

• Blood glucose concentration governs glycogen synthesis and degradation.
• High glucose activates glycogen synthesis (mostly in the liver) and inhibits glycogen breakdown;
• Low glucose activates glycogen breakdown (in the liver and muscles).
• Hormones like insulin and glucagon control glycogen metabolism.

Mechanism of Glycogen Enzyme Action

• Glycogen enzymes are regulated through covalent modification (phosphorylation/dephosphorylation) of their structures.
• Phosphorylation activates enzymes involved in glycogen breakdown (e.g., phosphorylase) and deactivates those involved in synthesis (e.g., synthase).

High Glucose and Insulin

• When blood glucose is high, insulin increases glycogen synthesis and inhibits glycogen phosphorylase kinase, hence, no glycogenolysis.

Regulation of Glycogen Synthesis and Degradation

• Blood glucose concentration is the key regulator. High glucose prefers glycogen synthesis, and low glucose promotes glycogenolysis.

Glycogen Storage Diseases

• Genetic deficiencies in glycogen metabolism cause glycogen storage diseases.
• Affected organs and symptoms depend on the specific enzyme deficiency.

Clinical notes - Glycogen Storage Diseases

• Various glycogen storage diseases are associated with specific enzymatic defects and organ-specific symptoms.

Further Information

• Further detail on specific enzyme defects and their roles in glycogen synthesis and degradation is also provided in the given notes.