CARBOHYDRATE METABOLISM

CARBOHYDRATE METABOLISM

Lecture Outline

  • Carbohydrate Digestion and Absorption

  • Glycolysis and Gluconeogenesis

  • Glycogenesis and Glycogenolysis

Carbohydrate Digestion

Mouth

  • Mastication: Food is mechanically broken down in the oral cavity and forms a bolus that enters the esophagus.

  • Salivary Amylase: Enzyme responsible for the hydrolysis of α-glycosidic linkages in starch and glycogen, resulting in the production of smaller polysaccharides and disaccharides, particularly maltose.

  • Absorption: Minimal absorption occurs during this phase as food is swallowed quickly.

Stomach

  • Inactivation of Salivary Amylase: The acidity within the stomach (pH level) inactivates salivary amylase.

  • Absence of Carbohydrate-Digesting Enzymes: Stomach content (chyme) is formed through the interaction of food with hydrochloric acid (HCl) and other enzymes. Some amino acid absorption occurs here.

Route of Absorption

Small Intestine

  • Bile Release: Upon entering the small intestine, bile is released, which neutralizes the gastric juices' pH and emulsifies lipids for absorption.

  • Pancreatic α-Amylase: Enzyme that breaks down polysaccharide chains into disaccharides, mainly maltose.

Outer Membrane of Intestinal Mucosal Cells

  • Disaccharidase Enzymes: These enzymes convert disaccharides into monosaccharides:

    • Maltase: Converts maltose to glucose.

    • Sucrase: Converts sucrose to glucose and fructose.

    • Lactase: Converts lactose to glucose and galactose.

  • Absorption: Major absorption of monosaccharides occurs in both the small and large intestines, facilitated by enzymes and intestinal microbiota.

Bloodstream Absorption

  • Monosaccharides: Products of carbohydrate digestion, such as glucose, galactose, and fructose, are absorbed into the bloodstream through the intestinal wall.

  • Intestinal Villi: These structures are rich in blood capillaries that facilitate the active transport of monosaccharides.

  • Conversion in Liver: Galactose and fructose undergo conversion to forms that participate in glucose metabolism in the liver.

Glycolysis: Breakdown of Glucose

  • Overview: Glycolysis converts one molecule of glucose into two molecules of pyruvate (a C3 molecule), producing ATP and NADH-reduced coenzymes in the process.

  • Stages: Occurs in two main stages:

    • Energy Investment Stage (Six-carbon stage)

    • Energy Production Stage (Three-carbon stage)

  • Committed Steps: Certain irreversible reactions that usually involve phosphate group addition/removal or CoA are termed committed steps in metabolic pathways.

Glycolysis Pathway Steps

  1. Formation of Glucose 6-Phosphate

    • Phosphorylation Reaction: A phosphate group from ATP is attached to the hydroxyl group on carbon 6 of glucose.

    • Catalyst: Enzyme involved is hexokinase; energy required is derived from ATP hydrolysis.

  2. Formation of Fructose 6-Phosphate

    • Isomerization: Glucose 6-phosphate is converted to fructose 6-phosphate.

    • Catalyst: Catalyzed by phosphoglucoisomerase.

  3. Formation of Fructose 1,6-Bisphosphate

    • Phosphorylation Reaction: ATP is used, as energy is derived from ATP hydrolysis.

    • Catalyst: Phosphofructokinase.

  4. Formation of Two Triose Phosphates

    • Cleavage Reaction: The C6 biphosphate is split into two C3 monophosphate species (dihydroxyacetone phosphate and glyceraldehyde 3-phosphate).

    • Catalyst: Aldolase.

  5. Formation of Glyceraldehyde 3-Phosphate

    • Isomerization: Dihydroxyacetone phosphate is converted to glyceraldehyde 3-phosphate.

    • Catalyst: Triosephosphate isomerase.

  6. Formation of 1,3-Bisphosphoglycerate

    • Reaction: A NADH molecule is produced; energy source is inorganic phosphate (Pi).

    • Catalyst: Glyceraldehyde 3-phosphate dehydrogenase joins a carboxylate ion and phosphate.

  7. Formation of 3-Phosphoglycerate

    • Conversion: A diphosphate species is converted back to a monophosphate species, generating ATP.

    • Catalyst: Phosphoglycerokinase; two ATP produced per glucose molecule.

  8. Formation of 2-Phosphoglycerate

    • Isomerization: Involves moving the phosphate group from carbon 3 to carbon 2.

    • Catalyst: Phosphoglyceromutase.

  9. Formation of Phosphoenolpyruvate

    • Dehydration Reaction: Results in high-energy compound formation.

    • Catalyst: Enolase.

  10. Formation of Pyruvate

    • ATP Production Step: High-energy phosphate group from phosphoenolpyruvate is transferred to ADP, forming ATP and pyruvate.

    • Catalyst: Pyruvate kinase; two ATP produced for each original glucose molecule.

Summary of ATP Production in Glycolysis

  • Overall Equation: The overall process can be summarized as:
    ext1glucose+2extNAD++2extADP+2extPi<br>ightarrow2extpyruvate+2extNADH+2extATP+2extH++2extH2extOext{1 glucose} + 2 ext{NAD}^+ + 2 ext{ADP} + 2 ext{Pi} <br>ightarrow 2 ext{pyruvate} + 2 ext{NADH} + 2 ext{ATP} + 2 ext{H}^+ + 2 ext{H}_2 ext{O}

Entry Points in Glycolysis

  • Fructose and Galactose Conversion:

    • Fructose enters glycolysis via phosphorylation to produce fructose 1-phosphate and subsequently is converted to glyceraldehyde and dihydroxyacetone phosphate.

    • Galactose is converted to glucose 1-phosphate, followed by conversion to glucose 6-phosphate.

Regulation of Glycolysis

  • Step 1 - Hexokinase: Inhibited by glucose 6-phosphate (feedback inhibition).

  • Step 3 - Phosphofructokinase: Inhibited by high ATP and citrate concentrations.

  • Step 10 - Pyruvate Kinase: Inhibited by high ATP concentrations; both phosphofructokinase (Step 3) and pyruvate kinase (Step 10) are allosteric enzymes.

Fates of Pyruvate

  1. Oxidation to Acetyl CoA

    • Under aerobic conditions, pyruvate is transformed into acetyl CoA via pyruvate dehydrogenase complex, entering the citric acid cycle.

    • Pyruvate traverses mitochondrial membranes to reach the mitochondrial matrix.

  2. Lactate Fermentation

    • Anaerobic reduction of pyruvate to lactate occurs primarily in muscle tissues, allowing glycolysis to persist by regenerating NAD+.

    • Lactate can revert back to pyruvate upon restoration of aerobic conditions, with lactate accumulation linked to muscle fatigue during intense exercise.

  3. Ethanol Fermentation

    • Anaerobic conversion of pyruvate to ethanol and carbon dioxide, occurring mainly in yeast. This process is fundamental in the production of alcoholic beverages and bread-making.

    • Steps: Involves decarboxylation to yield acetaldehyde, followed by reduction to ethanol.

Glycogenesis: Building up of Glycogen

Glycogen Structure

  • Definition: Glycogen is the branched polymeric form of glucose and serves as a carbohydrate storage form in humans and animals.

  • Function:

    • In muscle tissue, glycogen serves as a glucose source for glycolysis.

    • In liver tissue, it provides glucose crucial for maintaining normal blood glucose levels.

Glycogenesis Process
Steps:

  1. Formation of Glucose 1-Phosphate

    • Starting material is glucose 6-phosphate, catalyzed by phosphoglucomutase.

  2. Formation of UDP-Glucose

    • Activated high-energy compound UTP catalyzes the conversion of glucose 1-phosphate to uridine diphosphate glucose (UDP-glucose).

  3. Glucose Transfer to Glycogen Chain

    • Glucose from UDP-glucose is added to a glycogen chain while producing UDP, which subsequently reacts with ATP to form UTP and ADP.

    • Two ATP molecules are required for adding a single glucose unit into glycogen chain.

Glycogenolysis: Breakdown of Glycogen

Glycogenolysis Process

  • Occurs when blood glucose levels decline, utilizing stored glycogen to replenish levels, with glucose 6-phosphate entering glycolysis directly.

Steps:

  1. Phosphorylation of a Glucose Unit

    • Glycogen phosphorylase catalyzes the removal of an end glucose unit, generating glucose 1-phosphate.

  2. Isomerization of Glucose 1-Phosphate

    • Phosphoglucomutase catalyzes isomerization of glucose 1-phosphate, moving the phosphate group to the carbon 6 position, effectively reversing glycogenesis.

Gluconeogenesis: Synthesis of Glucose

  • Definition: Gluconeogenesis is a metabolic pathway that synthesizes glucose from non-carbohydrate sources.

  • Non-Carbohydrate Precursors:

    • Pyruvate

    • Lactate (from muscles and red blood cells)

    • Glycerol (from triacylglycerol hydrolysis)

    • Glucogenic amino acids (from protein breakdown during starvation).

  • Location: Approximately 90% of gluconeogenesis occurs in the liver.

  • Indications for Gluconeogenesis: Becomes necessary to replenish liver glycogen stores, convert lactate back to glucose post-exercise, and maintain glucose levels when glycogen is depleted.

  • Energy Requirements: Converting pyruvate to glucose requires the expenditure of 4 ATP, 2 GTP, and associated NADH.

  • Bypassing Irreversible Glycolytic Steps: Gluconeogenesis circumvents three irreversible steps in glycolysis. These involve:

    • Conversion of pyruvate to PEP through oxaloacetate via pyruvate carboxylase and PEP carboxykinase.

    • Dephosphorylation of fructose 1,6-bisphosphate via FBPase-1.

    • Dephosphorylation of glucose 6-phosphate via glucose 6-phosphatase.

  • Overall Requirement for Glucose Synthesis from Pyruvate: This process demands 4 ATP, 2 GTP, and 2 NADH.

Relationships Among Metabolic Pathways Involving Glucose

  • These pathways include glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis, demonstrating interconnected roles of these various metabolic processes in glucose homeostasis.

 
This study guide comprehensively covers carbohydrate metabolism, detailing digestion, absorption, glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis, thereby providing a complete understanding of these interconnected biological processes.