Carbohydrate Metabolism Overview

Carbohydrate Metabolism

• Metabolism is the sum of the biochemical reactions in an organism, including coordination, regulation, and energy needs.
• It consists of two major parts: catabolism and anabolism.
• Catabolism: the breakdown of larger molecules into smaller ones, releasing energy (oxidative process).
• Anabolism: the synthesis of larger molecules from smaller ones, requiring energy (reductive process).
• Metabolic pathways are sequences of reactions where the product of one reaction becomes the substrate for the next.
• Linear, cyclic, branched (converging/diverging), and spiral pathways are different types of metabolic pathways.
• Metabolites are intermediates in metabolic pathways.

Terminology of Metabolism

• Photosynthesis: 6 CO2 + 6 H2O → C6H12O6 + 6 O2 (anabolic)
• Respiration: C6H12O6 + 6 O2 → 6 CO2 + 6 H2O (catabolic)

Role of Oxidation and Reduction in Metabolism

• Oxidation-reduction (redox) reactions involve electron transfer.
• Oxidation: loss of electrons (reducing agent).
• Reduction: gain of electrons (oxidizing agent).

Oxidation and Reduction in Metabolism (Example: Ethanol)

• NAD+ + 2e- + H+ → NADH(reduced)
• CH3CH2OH (ethanol) + NAD+ → CH3CHO (acetaldehyde) + NADH + H+
• CH3CHO(acetaldhyde) + NADH + H+ → CH3CH2OH(ethanol) + NAD+

Oxidation and Reduction in Metabolism (Example: Pyruvate)

• NADH + H+ + pyruvate → lactate + NAD+

Metabolic Pathways

• Enzymes: groups of noncovalently associated enzymes that catalyze two or more sequential steps in a metabolic pathway.
• Multienzymes (components of a metabolic pathway): coordinated groups of enzymes that carry out these functions.
• Coenzymes: organic molecules that assist enzymes in their function.
• ATP (adenosine triphosphate): produced or used in metabolic pathways for energy.

Metabolism Regulation

• Feedback inhibition: the product of a pathway inhibits an earlier step in the pathway.
• Feed-forward activation: a metabolite produced early in the pathway activates an enzyme further down the pathway.

Coenzymes

• NAD+/NADH: electron carriers involved in redox reactions.
• NADP+/NADPH: electron carriers involved in biosynthesis, similar to NADH.
• FAD/FADH2: electron carriers; accept one or two electrons at a time.
• Coenzyme A (CoASH): activates metabolites.

NAD+/NADH

• Nicotinamide adenine dinucleotide (NAD+) is a coenzyme.
• Acts as a biological oxidizing agent.
• Consists of a nicotinamide portion.
• NAD+ is a two-electron oxidizing agent that is reduced to NADH.

NADP+/NADPH

• Nicotinamide adenine dinucleotide phosphate (NADP+) is a coenzyme.
• NADP+ acts as a biological oxidizing agent and is reduced to form NADPH, which is involved in reductive biosynthesis processes.
• It differs from NAD+ by a phosphate group on its ribose.

FAD/FADH2

• Flavin adenine dinucleotide (FAD) is an important coenzyme, accepting one or two electrons at a time , involved in oxidation-reduction reactions.

Coenzyme A

• Coenzyme A (CoASH) is a coenzyme that acts as a carrier for acetyl and other acyl groups in metabolic pathways.
• The thioester bond in acetyl-CoA is a high-energy bond; hydrolysis releases energy.

ATP - High-Energy Compound

• ATP is an essential high-energy bond-containing compound.
• Phosphorylation of ADP to ATP requires energy input.
• Hydrolysis of ATP to ADP releases energy.

High-Energy Bonds in ATP

• Phosphoanhydride bonds in ATP are high-energy bonds.
• These bonds release or require convenient amounts of energy in reactions.
• Couple reactions use energy released by one reaction (such as ATP hydrolysis) to provide energy for another reaction.

Couple Reactions - Example

• Energy release from ATP hydrolysis can drive other energy-requiring reactions.
• Various examples of coupled reactions (energy-requiring and releasing reactions) are mentioned in the provided text in context with glucose.

Breakdown of Glucose to Generate Energy (Respiration)

• Two processes: anaerobic respiration and aerobic respiration.
• Anaerobic respiration: glycolysis → fermentation (lactic acid or alcohol).
• Aerobic respiration: glycolysis → oxidative decarboxylation → citric acid cycle → oxidative phosphorylation.

Aerobic Respiration Stages

• Oxidative decarboxylation of pyruvate.
• Citric acid cycle(TCA cycle).
• Oxidative phosphorylation/electron transport chain(ETC).

Glycolysis

• The first stage of glucose metabolism.
• Converts 1 glucose molecule into 2 pyruvate molecules.
• Involves 10 enzymatic steps.
• Has two phases (energy investment and energy recovery).
• Generates a net gain of 2 ATP molecules, 2 NADH+H+ molecules per glucose molecule.
• In anaerobic conditions, pyruvate is converted into lactate(muscle cells) or ethanol (yeast/bacteria).

Glycolysis- Detailed Stages

• Glucose is phosphorylated—initiating the glycolysis pathway.
• Glucose-phosphate is isomerized to fructose-6-phosphate
• Fructose-6-phosphate is phosphorylated to fructose-1,6-bisphosphate.
• Fructose-1,6-bisphosphate is split into two 3-carbon fragments.
• Dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate.
• Glyceraldehyde-3-phosphate is converted to 1,3-bisphosphoglycerate, with an oxidation-reduction reaction involving NAD+ and NADH.
• 1,3-bisphosphoglycerate is converted to 3-phosphoglycerate, and ATP is produced.
• 3-phosphoglycerate is converted to 2-phosphoglycerate.
• 2-phosphoglycerate is dehydrated to phosphoenolpyruvate.
• Phosphoenolpyruvate is converted to pyruvate, producing ATP.

Fates of Pyruvate

• Aerobic conditions: pyruvate enters the citric acid cycle.
• Anaerobic conditions: pyruvate is converted to lactate(muscles) or ethanol (yeast and bacteria).

Glycolysis Control Points

• Glucose-6-phosphate.
• Fructose-6-phosphate.
• Fructose-1,6-bisphosphate.
• Glyceraldehyde-3-phosphate.
• 1,3-bisphosphoglycerate.
• 3-phosphoglycerate.
• 2-phosphoglycerate.
• Phosphoenolpyruvate.
• Pyruvate.

ATP Production

• ATP is produced by substrate-level phosphorylation during glycolysis (steps 7 and 10).
• 1,3-bisphosphoglycerate and phosphoenolpyruvate are high-energy intermediates involved in substrate-level phosphorylation to generate ATP.
• Oxidative phosphorylation is the process of ATP production in the electron transport chain.

Anaerobic Metabolism of Pyruvate

• Under anaerobic conditions, the most important pathway for regenerating NAD+ is the reduction of pyruvate to lactate by lactate dehydrogenase.
• This occurs in muscle tissue under strenuous exercise when oxygen supply is limited.

Alcoholic Fermentation

• Decarboxylation of pyruvate to acetaldehyde occurs, followed by reduction to ethanol.
• Pyruvate decarboxylase catalyzes decarboxylation, requiring Mg2+ and thiamine pyrophosphate (TPP).
• Alcohol dehydrogenase catalyzes the conversion to ethanol.

Gluconeogenesis

• The process of synthesizing glucose from non-carbohydrate precursors.
• It involves a different set of enzymes than those used in glycolysis, and some steps are irreversible, so it has to go through alternative steps that bypass those irreversible steps in glycolysis.
• Includes 9 steps that occur mainly in liver and kidney.
• Used to maintain blood glucose levels when glycogen stores are depleted.

Gluconeogenesis - Different Steps

• Conversion of pyruvate to Oxaloacetate, through pyruvate carboxylase enzyme.

Controlling Glucose Metabolism

• Glycolysis and gluconeogenesis are not simultaneously active.
• Regulation of cellular activity of both pathways ensures enough ATP availability to the cell.
• Cori cycle: cycling of glucose between muscle and liver via glycolysis and gluconeoesis, maintaining blood glucose levels and handling lactate from muscle under anerobic condition.

The Citric Acid Cycle (TCA Cycle)

• Circular pathway involving eight reactions.
• Acetyl-CoA is needed to begin the cycle.
• Eight enzymes are involved.
• Generates 3 NADH, 1 FADH2, 2 CO2, and 1 GTP (equivalent to 1 ATP) per acetyl-CoA molecule.

Citric Acid Cycle Steps

• Formation of Citrate.
• Isomerization to Isocitrate.
• First oxidation reaction: Formation of α-Ketoglutarate and CO2
• Second oxidation reaction: Formation of Succinyl-CoA and CO2
• Formation of Succinate.
• Formation of Fumarate: FAD-linked oxidation.
• Formation of L-Malate
• Regeneration of Oxaloacetate: Final oxidation step.

Regulation of TCA Cycle

• Various steps have control points where the reactions are regulated.

Fluorocitrate

• A potent poison that inhibits mitochondrial oxidative metabolism.
• Blocks the Krebs cycle by inhibiting aconitase.