Energy Transformation: Cellular Respiration Outline

1. Energy and carbon sources in living cells 2. Sources of cellular ATP 3. Turning chemical energy of covalent bonds between C-C into

energy for cellular work (ATP) 4. Importance of electrons and H atoms in oxidation-reduction

reactions in biological systems 5. Cellular mechanisms of ATP generation 6. The four major central metabolic pathways

Glycolysis- Fermentation Transition step Krebs Cycle Electron Transport chain and oxidative phosphorylation

4. Poisons of cellular respiration and their mechanisms of action. 5. Use of biomolecules other than glucose as carbon skeletons &

energy sources

http://health.howstuffworks.com/sports-physiology3.htm

A cell has enough ATP to last for about three seconds

Necessary ATP is supplied to muscle cells by

1. Phosphagen system (8 to 10 seconds.) 2. Glycogen-lactic acid system (90 seconds)- glucose 3. Aerobic Respiration (unlimited)- glucose

Phosphagen system (muscle fibers)

(*) Arezki Azzi et al. Protein Sci 2004; 13: 575-585

• Creatine phosphate contains (a high-energy phosphate compound).

• Creatine kinase transfers the phosphate to ADP to form ATP.

Creatine-Phosphate (tri)

*

Creatine-Phosphate + ADP (Tri)

Creatine-Phosphate + ATP (Di)

Creatine Kinase

During cellular respiration the potential energy in the chemical bonds holding C atoms in organic molecules in turned into ATP.

In presence of oxygen complete breakdown

C-C-C-C-C-C + O2……………… CO2 + H2O + ATP large amount

In absence of oxygen

incomplete breakdown C-C-C-C-C-C ……………… 2 C-C-C + ATP

small amount

Cellular respiration: ATP is produced aerobically, in the presence of oxygen

Fermentation: ATP is produced anaerobically, in the absence of oxygen

Chemical bonds of organic molecules

Chemical bonds involve electrons of atoms Electrons have energy Chemical bonds are forms of potential energy If a molecule loses an electron does it lose energy? When a chemical bond is broken sometimes electrons can be released

• Oxidation: removal of electrons. • Reduction: gain of electrons. • Redox reaction: oxidation reaction paired with a

reduction reaction.

Oxidation-Reduction

The electrons associated with hydrogen atoms. Biological oxidations are often dehydrogenations

Soluble electron carriers NAD+, and FAD (ATP generation) NADP+ (biosynthetic reactions)

Electron Carriers in Biological Systems

Nicotinamide Adenine Dinucleotide (NAD+) a co-enzyme that acts as an electron shuttle (Niacin)

NAD+

Nicotinamide (oxidized form)

Dehydrogenase

2 e– + 2 H+

2 e– + H+

NADH H+

H+

Nicotinamide (reduced form)

+ 2[H] (from food)

+

Flavin Adenine Dinucleotide (FAD+) is another co-enzyme that acts as an electron shuttle (Vitamin B2)

In Metabolic pathways

Oxidation Reduction

- Energy loss or gain - Endergonic or exergonic

In cells, energy is harvested from an energy source (organic molecule) by a series of coupled oxidation/reduction reactions (redox) known as the central metabolic pathways

becomes oxidized

becomes reduced

Dehydrogenase

Metabolic Pathways Linear Metabolic Pathways

Branched Metabolic Pathways

Cyclic Metabolic Pathways

The Endo-symbiotic Theory: Origin of Eukaryotes

An overview of the central metabolic pathways • Glycolysis • Transition step • Tricarboxylic acid cycle (TCA or Krebs cycle) • The Electron Transport Chain and oxidative

phosphorylation

2. Oxidative phosphorylation/ Chemiosmosis

Mechanisms of ATP Generation during cellular respiration

• ADP and inorganic PO-4

• ATP synthase • Cellular respiration in mitochondria • Electron Transport Chain

Glycolysis

• Multi – step breakdown of glucose into intermediates

• Turns one glucose (6-carbon) into two pyruvate (3-carbon) molecules

• Generates a small amount of ATP (substrate- level phosphorylation)

• Generates reducing power - NADH + H+

1. Substrate-level phosphorylation

Generation of ATP

-Transfer of a high-energy PO4 from an organic molecule to ADP - Different enzymes - During glycolysis and the TCA or Krebs cycle

-

Figure 9.18 Pyruvate as a key juncture in catabolism

Mitochondrion

Fermentation

• An extension of glycolysis • Takes place in the absence of oxygen (anaerobic) • Regenerates NAD+ from NADH + H +

• ATP generated by substrate - level phosphorylation during glycolysis

• Does not use the Krebs cycle or ETC (no oxidative - phosphorylation)

• A diversity of end products produced (i.e. lactic acid, alcohols, etc.)

Figure 9.17a Fermentation

Figure 9.17b Fermentation

Figure 9.9 A closer look at glycolysis: energy investment phase

Figure 9.9 A closer look at glycolysis: energy payoff phase

Energy investment phase

Glucose

2 ATP used 2 ADP + 2 P

4 ADP + 4 P 4 ATP formed

2 NAD+ + 4 e– + 4 H+

Energy payoff phase

2 NADH + 2 H+

2 Pyruvate + 2 H2O

Net

2 Pyruvate + 2 H2O

2 ATP

2 NADH + 2 H+

Glucose

4 ATP formed – 2 ATP used

2 NAD+ + 4 e– + 4 H+

Glycolysis Citric acid cycle

Oxidative phosphorylation

ATP ATP ATP

The energy input and output of glycolysis

Transition step

• Under aerobic conditions, the pyruvate produced during glycolysis is directed to the mitochondrion.

• A multi-enzyme complex, spanning the 2 mitochondrial membranes, turns pyruvate (3-carbon) into Acetyl-CoA (2-carbon) and releases one CO2 molecule

• Uses coenzyme A (Vit B derivative) • Generates reducing power NADH + H+

Figure 9.10 Conversion of pyruvate to acetyl CoA, the junction between glycolysis and the Krebs cycle

Krebs or TCA Cycle

• A cyclical pathway • Accepts – acetyl – CoA • Generates 2 – CO2 molecules (for every acetyl-CoA • Generates reducing power NADH + H+ and FADH2

• Generates a small amount of ATP (substrate-level phosphorylation)

A closer look at the Krebs cycle

TP Q 9

Figure 9.12 A summary of the transition step and Krebs cycle

Figure 9.5 An introduction to electron transport chains

Electron Transport Chain and ATP generation

Electron transport chain: • membrane-embedded or

bound electron carriers • Mostly proteins with non-

protein groups. • NADH vs. FADH2

• No direct formation of ATP • Pumps H+ into the inter-

membrane space

2. Oxidative phosphorylation/ Chemiosmosis

ATP Generation during aerobic cellular respiration

• ADP and inorganic PO-4

• ATP synthase • Cellular respiration in mitochondria • Electron Transport Chain

Oxidative Phosphorylation and ATP generation

ATP Generation : • Membrane-embedded protein complex , ATP

synthase • Proton-motive force • Direct formation of ATP by Chemiosmosis Chemiosmosis: the coupling of the transport of

H+ across membrane by facilitated diffusion with chemical reaction producing ATP

Electron Transport chains and oxidative phosphorylation http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter9/animations.html# ATP Synthase Gradient: The Movie http://vcell.ndsu.edu/animations/at pgradient/movie.htm

Chemiosmosis couples the electron transport chain to ATP synthesis

Certain poisons interrupt critical events in cellular respiration • Block the movement of electrons • Block the flow of H+ through ATP synthase • Allow H+ to leak through the membrane

H+

H+

H+

H+

H+

H+ H+ H+ H+

+ 2 H+

H+

H+ H+

1 O2 2

H O 2 ADP + P ATP

NADH FADH2

NAD+

FAD

Rotenone Cyanide, carbon monoxide

Oligomycin

DNP

ATP Synthase

Electron Transport Chain Chemiosmosis

Energy yield: How many ATP molecules are generated during cellular respiration of a single glucose molecule?

Metabolic Disorders

http://www.merckmanuals.com/professional/pediatrics/inherited-disorders-of-metabolism/overview-of-carbohydrate-metabolism-disorders

Find out the Specific defect Symptoms

1. Pyruvate dehydrogenase deficiency (Transition Step) 2. Mitochondrial Oxidative Phosphorylation Disorders

Sources of cellular glucose

• glucose from food in the intestine • glycogen supplies in the muscles • breakdown of the Liver's glycogen into

glucose

The Catabolism of various food molecules

Beta oxidation

http://www.brookscole. com/chemistry_d/templ ates/student_resources /shared_resources/ani mations/carnitine/carni tine1.html

• Triglycerides consist of glycerol and fatty acids • Fatty acids broken down into through beta

oxidation

Simple lipids

Proteins

Protein Amino acids Extracellular proteases

Krebs cycle and glycolysis Transition step

Deamination, decarboxylation, dehydrogenation Organic acid

Feedback control of cellular respiration

Phosphofructokinase

Allosteric enzyme

Activity modulated by inhibitors and activators

Adjustment of cellular respiration in response to demand

OXIDATIVE PHOSPHORYLATION (Electron Transport and Chemiosmosis)

Food, such as peanuts

Carbohydrates Fats Proteins

Sugars Glycerol Fatty acids Amino acids

Amino groups

Glucose G3P Pyruvate Acetyl CoA

CITRIC ACID CYCLE

ATP

GLYCOLYSIS

Food molecules provide raw materials for biosynthesis consuming ATP

ATP needed to drive biosynthesis

ATP

CITRIC ACID CYCLE

GLUCOSE SYNTHESIS G3P

Acetyl CoA Pyruvate Glucose

Amino groups

Amino acids Fatty acids

Glycerol Sugars

Carbohydrates Fats Proteins

Cells, tissues, organisms