Cell Biology- Chapter 13

Glycolysis and Fatty Acid Oxidation

Biological oxidations capture energy from molecules in multiple steps

Animals break down food in 3 stages

• macronutrients need to be consumed in large amounts, used as energy sources

• micronutrients are needed in small amounts, often coenzymes

• Nutrient acquisition begins with mechanical and chemical breakdown of food into parts.

• proteins become animo acids

• polysaccharides become simple sugars

• fats into fatty acids and glycerol

• Nutrients enter cellular metabolism at multiple points and locations

• sugar processed in cytosol

• fats processed in peroxisomes and mitochondrion

• Amino acids are processed in the cytosol and mitochondrion

• Nutrients can be altered to produce needed macromolecule precursors or fed into oxidative catabolism

• full oxidation requires oxygen, but cells have anaerobic means of extracting energy

Glycolysis splits a glucose into 2 pyruvate molecules

• glycolysis requires a supply of 2 ATP and NAD+

• splits a glucose to two 3-carbon pyruvate molecules

Multiple steps of glycolysis can be divided into 3 main phases

• energy investment: formation of 2 intermediates, needs 2 ATP as energy

• 3 carbon sugar generation

• energy payoff phase produces 4 ATPS

Steps of glycolysis: 1- glucose phosphorylation

• direct removal of the phosphate is spontaneous, though only lover cells express enzyme that catalyzes it

Step 2: glucose 6 phosphate isomerization

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Step 3: Fructose phosphorylation

Step 4: fructose, 1, 6 biphosphate lysis

Step 5: Dihydroxyacetone phosphate isomerization

Step 6: Glyceraldehyde 3- phosphate oxidation

Step 7: 1,3-biphosphoglycerate dephosphorylation (and ATP synthesis)

Fermentation ensures an adequate supply of NAD+ when activity exceeds oxygen availability

• sufficient NAD+ is essential to progression to the energy payoff phase of glycolysis

• Aerobic respiration can regenerate NAD+, but it requires oxygen

• When oxygen is low, fermentation can regenerate NAD+ via reduction of pyruvate to lactate

• lactate fermentation is performed by animals and some bacteria

• controlled bacterial fermentation of milk is how yogurt is made

Some species of yeast ferment pyruvate to ethanol

Step 8: 3-phosphoglycerate mutation

Step 9: 2-phosphoglycerate dehydration

• enolase removes water

Step 10: phosphoenolpyruvate dephosphorylation (and ATP synthesis)

Pyruvate from glycolysis is changed to acetyl CoA

• pyruvate processed by pyruvate dehydrogenase complex located in mitochondrial matrix

• complex members remove CO2 from pyruvate, reduce NAD+, and link remaining 2 carbon acetyl group to coenzyme A

Fatty Acid oxidation produces activated carriers as acetyl CoA

Citric Acid Cycle and Regulation of Metabolism

Step-wise oxidation reactions of the citric acid cycle produce activated carriers

Steps of the citric acid cycle:

Formation of Citrate: Acetyl-CoA combines with oxaloacetate to form citrate, catalyzed by the enzyme citrate synthase.

1. Formation of Isocitrate: Citrate is converted into its isomer, isocitrate, through the enzyme aconitase.

2. Oxidation to α-Ketoglutarate: Isocitrate is oxidized to α-ketoglutarate, producing NADH and CO₂, catalyzed by isocitrate dehydrogenase.

3. Formation of Succinyl-CoA: α-Ketoglutarate is further oxidized to succinyl-CoA, producing NADH and CO₂, catalyzed by α-ketoglutarate dehydrogenase.

4. Conversion to Succinate: Succinyl-CoA is converted to succinate, producing GTP (or ATP), catalyzed by succinyl-CoA synthetase.

5. Oxidation to Fumarate: Succinate is oxidized to fumarate, producing FADH₂, catalyzed by succinate dehydrogenase.

6. Hydration to Malate: Fumarate is hydrated to malate, catalyzed by fumarase.

7. Oxidation to Oxaloacetate: Malate is oxidized to oxaloacetate, producing NADH, catalyzed by malate dehydrogenase.

Transfer of energy from electron carriers to ATP requires oxygen

• each molecule of pyruvate delivers 2 carbons to the citric acid cycle

• one carbon is lost in the form of CO2 during conversion of pyruvate to acetyl-coA

• CO2 is ejected at later stages, but these molecules are not from initial pyruvate

• it takes 3 cycles for the pyruvate-derived carbons to be released

• oxygen is required- final electron acceptor

• most energy recovered during citric acid cycle is in form of reduced electron carriers

Deriving nature of citric acid cycle

• used a manometer to measure pressure changes

If pyruvate isn’t limiting, adding any intermediate accelerates the entire cycle

Gluconeogenesis runs on glycolysis backwards to produce glucose molecules

• many pathways converge on the citric acid cycle, so interconversion between different types of nutrients is possible

• liver cells have the necessary enzymes to run glycolysis backwards to make glucose from other metabolites

• the process of gluconeogenesis ends to dephosphorylation glucose-6-phosphate to produce free glucose.

Some cells can store glucose in the form of glycogen polymers

• muscle stores for its own use, liver stores glycogen for release to rest of body

• Energy can be stored for long periods as fat