Energy Transformation: Cellular Respiration Outline

1. Sources of cellular ATP 2. Turning chemical energy of covalent bonds between C-C into

energy for cellular work (ATP) 3. Importance of electrons and H atoms in oxidation-reduction

reactions in biological systems 4. Cellular mechanisms of ATP generation 5. 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)

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

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

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

Creatine-Phosphate (tri)

*

+ ADP Creatine-Phosphate (Tri)

Creatine-Phosphate (Di)

+ ATP

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)

Oxidation Reduction energy loss or gain energy loss or gain

Exergonic or endergonic Exergonic or endergonic

In Metabolic pathways

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 reduced

becomes oxidized

Dehydrogenase

1. Oxidative phosphorylation/ Chemiosmosis

Mechanisms of ATP Generation during cellular respiration

• ADP and inorganic PO-4 • ATP synthase • Cellular respiration in mitochondria • Electron Transport Chain

2. 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

Metabolic Pathways Linear Metabolic Pathways

Branched Metabolic Pathways

Cyclic Metabolic Pathways

• Glycolysis • Transition step • Tricarboxylic acid cycle (TCA or Krebs cycle) • The Electron Transport Chain and oxidative

phosphorylation

An overview of the central metabolic pathways

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+

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 H+ 2 NADH

2 Pyruvate + 2 H2O

2 Pyruvate + 2 H2O

2 ATP

2 NADH + 2 H+

Glucose

4 ATP formed – 2 ATP used

2 NAD+ + 4 e– + 4 H+

Net

Glycolysis Citric acid cycle

Oxidative phosphorylation

ATP ATP ATP

The energy input and output of glycolysis

Figure 9.18 Pyruvate as a key juncture in catabolism

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

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

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

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+

H+

H+

H+ H+

O2

H2O P ATP

NADH NAD+

FADH2 FAD

Rotenone Cyanide, carbon monoxide

Oligomycin

DNP

ATP Synthase

+ 2

ADP +

Electron Transport Chain Chemiosmosis

1 2

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

Sources of cellular glucose

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

glucose

Food for Thought!!!

You have a friend who lost 15 pounds of fat on a diet. Where did the fat go (how was it lost)?

The Catabolism of various food molecules

Beta oxidation

http://www.brookscole.com/chemistry_d/templates/student_resources/shared_resources/animations/carnitine/carnitine1.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 Acetyl

CoA Pyruvate G3P Glucose

Amino groups

Amino acids Fatty acids

Glycerol Sugars

Carbohydrates Fats Proteins

Cells, tissues, organisms