Cellular respiration (glycolysis, TCA and ETC)

NSB 211: DIGESTIVE SYSTEM NUTRITION AND METABOLISM

TOPIC;

•CELLULAR RESPIRATION

Lecturer: Dr. G. Kattam Maiyoh

04/12/23GKM/NSB 211: DIGESTIVE SYSTEM NUTRITION

AND METABOLISM/2013

Learning Objectives• Explain why cells need breakdown

biomolecules (E.G. glucose)• Describe the basic steps in;

– Glycolysis, – The TCA cycle, – The electron transport chain (ETC)

• Summarize the energy yield of all above steps cellular respiration

04/12/23 GKM/NSB 211: DIGESTIVE SYSTEM NUTRITION AND METABOLISM/2013

Overview of Cellular Respiration

• Cellular respiration is the step-wise release of energy from carbohydrates and other molecules; energy from these reactions is used to synthesize ATP molecules.

• This is an aerobic process that requires oxygen (O2) and gives off carbon dioxide (CO2), and involves the complete breakdown of glucose to carbon dioxide and water.

• Metabolism refers to all the chemical reactions of the body– some reactions produce the energy stored in

ATP that other reactions consume– all biological molecules will eventually be

broken down and recycled or excreted from the body

GKM/NSB 211: DIGESTIVE SYSTEM NUTRITION AND METABOLISM/201304/12/23

Catabolism and Anabolism• Catabolic reactions breakdown complex

organic compounds– providing energy (exergonic)– glycolysis, Krebs cycle and electron

transport

• Anabolic reactions synthesize complex molecules from small molecules – requiring energy (endergonic)

• Exchange of energy requires use of ATP (adenosine triphosphate) molecule.

ATP Molecule & Energy

• Each cell has about 1 billion ATP molecules that last for less than one minute

• Over half of the energy released from ATP is converted to heat

Mechanisms of ATP Generation

• Phosphorylation is the addition of phospahate group.– bond attaching 3rd phosphate group

contains stored energy • Mechanisms of phosphorylation

– within animals• substrate-level phosphorylation in cytosol• oxidative phosphorylation in mitochondria

– in chlorophyll-containing plants or bacteria

• photophosphorylation.GKM/NSB 211: DIGESTIVE SYSTEM

NUTRITION AND METABOLISM/201304/12/23

Phosphorylation in Animal Cells

• In cytoplasm (1)• In mitochondria (2, 3 & 4)

25-9GKM/NSB 211: DIGESTIVE SYSTEM

NUTRITION AND METABOLISM/201304/12/23

• (Insert Fig. 7.4a)

04/12/23 GKM/NSB 211: DIGESTIVE SYSTEM NUTRITION AND METABOLISM/2013 Sld 38

Carbohydrate Metabolism--In Review• In GI tract

– polysaccharides broken down into simple sugars – absorption of simple sugars (glucose, fructose &

galactose)

• In liver – fructose & galactose transformed into glucose– storage of glycogen (also in muscle)

• In body cells --functions of glucose– oxidized to produce energy– conversion into something else– storage energy as triglyceride in fat

Glucose Movement into Cells

• In GI tract and kidney tubules, Na+/glucose symporters

• Most other cells, GluT facilitated diffusion transporters move glucose into cells

• Glucose 6-phosphate forms immediately inside cell (requires ATP) thus, glucose hidden in cell

• Concentration gradient favorable for more glucose to enter

Glucose Catabolism

• Cellular respiration– 4 steps are involved

– glucose + O2 producesH2O + energy + CO2

• Anaerobic respiration– called glycolysis (1)– Results in formation of acetyl CoA (2)

is transitional step to Krebs cycle

• Aerobic respiration– Krebs cycle (3) and electron transport chain (4)

• Each step of cellular respiration requires a separate enzyme.

• Some enzymes use the oxidation-reduction coenzyme NAD+ (nicotinamide adenine dinucleotide).

• When a metabolite is oxidized, NAD+ accepts two electrons plus a hydrogen ion (H+) and NADH results; NAD+ can also reduce a metabolite by giving up electrons.

• FAD (flavin adenine dinucleotide) is sometimes used instead of NAD+.

Glycolysis takes place in the cytosol of cells.

Glucose enters the Glycolysis pathway by conversion to glucose-6-phosphate.

Initially there is energy input corresponding to cleavage of two ~P bonds of ATP.

CH2OPO32

glucose-6-phosphate

CH 2O H

CH 2O PO 32

A T P A D P

M g 2+

glucose g lucose -6 -phosphate

H ex ok inase

1. Hexokinase catalyzes: Glucose + ATP glucose-6-P + ADP

The reaction involves nucleophilic attack of the C6 hydroxyl O of glucose on P of the terminal phosphate of ATP.

ATP binds to the enzyme as a complex with Mg++.GKM/NSB 211: DIGESTIVE SYSTEM NUTRITION AND METABOLISM/2013

Glycolysis & Fate of Pyruvic Acid• Breakdown of six-carbon

glucose molecule into 2 three-carbon molecules of pyruvic acid– 10 step process

occurring in cell cytosol– produces 4 molecules of

ATP after input of 2 ATP– utilizes 2 NAD+

molecules as hydrogen acceptors

GKM/CHE 214/LEC 03/SEM 02/2011 25-18

10 Steps of Glycolysis

If O2 shortage in a cell

•Pyruvic acid is reduced to lactic acid so that NAD+ will be still available for further glycolysis•This process is known as fermentation•Lactic acid rapidly diffuses out of cell to blood•Liver cells remove it from blood & convert it back to pyruvic acid

Why does fermentation occur? Pyruvate is reduced to lactate when oxygen is not available because fermentation uses NADH and regenerates NAD+.

In this way NAD+ is now free to pick up more electrons during early steps of glycolysis; this keeps glycolysis going.

Fermentation-yeast

Lactic Acid or lactate-muscles

Two types of Anaerobic Respiration

Advantages and Disadvantages of Fermentation

• Fermentation can provide a rapid burst of ATP in muscle cells, even when oxygen is in limited supply.

• Lactate, however, is toxic to cells.• Initially, blood carries away lactate as it forms;

eventually lactate builds up, lowering cell pH, and causing muscles to fatigue.

• Oxygen debt occurs, and the liver must reconvert lactate to pyruvate.

Efficiency of Fermentation

• Two ATP produced during fermentation are equivalent to 14.6 kcal; complete oxidation of glucose to CO2 and H2O represents a yield of 686 kcal per molecule of glucose.

• Thus, fermentation is only 2.1% efficient compared to cellular respiration.

• (14.6/686) x 100 = 2.1%

Glycolysis summary

•Inputs:•Glucose•2 NAD+•2 ATP

•4 ADP + 2 P

•Outputs:•2 pyruvate

•2 NADH•2 ADP

•2 ATP (net gain)

Transition Reaction• The transition reaction connects glycolysis to

the citric acid cycle, and is thus the transition between these two pathways.

• Pyruvate is converted to a C2 acetyl group attached to coenzyme A (CoA), and CO2 is released.

• During this oxidation reaction, NAD+ is converted to NADH + H+; the transition reaction occurs twice per glucose molecule.

Formation of Acetyl Coenzyme A• Pyruvic acid enters the

mitochondria with help of transporter protein

• Decarboxylation– pyruvate dehydrogenase

converts 3 carbon pyruvic acid to 2 carbon fragment (CO2 produced)

– pyruvic acid is oxidized so that NAD+ becomes NADH

• 2 carbon fragment (acetyl group) is attached to Coenzyme A to form Acetyl coenzyme A which enter Krebs cycle– coenzyme A is derived from

pantothenic acid (B vitamin).GKM/NSB 211: DIGESTIVE SYSTEM NUTRITION AND METABOLISM/201304/12/23

GKM/NSB 211: DIGESTIVE SYSTEM NUTRITION AND METABOLISM/2013

Krebs Cycle (Citric Acid Cycle)• Citric acid cycle – a cyclical oxidation-

reduction & decarboxylation reactions occurring in matrix of mitochondria

• Gives off CO2 and produce one ATP per cycle; occurs twice per glucose molecule

• It finishes the same as it starts (4C)– acetyl CoA (2C) enters at top & combines with a

4C compound– 2 decarboxylation reactions peel 2 carbons off

again when CO2 is formed

The names of the various enzymes in the previous slide are indicated in the figure below

THE TCATHE TCA

• During the cycle, oxidation occurs when NAD+ accepts electrons in three sites and FAD accepts electrons once.

• A gain of one ATP per every turn of the cycle; it turns twice per glucose.

• During the citric acid cycle, the six carbon atoms in glucose become CO2.

• The transition reaction produces two CO2, and the citric acid cycle produces four CO2 per molecule of glucose.

What happens in the cycle?

Products of the Krebs Cycle• Energy stored in bonds is released step by step to

form several reduced coenzymes (NADH & FADH2) that store the energy

• In summary: each Acetyl CoAmolecule that enters the Krebscycle produces yields;

– 2 molecules of CO2

• one reason O2 is needed

– 3 molecules of NADH + H+– one molecule of ATP

– one molecule of FADH2

• Remember, each glucoseproduced 2 acetyl CoA molecules

Citric acid cycle inputs and outputs per glucose molecule

•Inputs:•2 acetyl groups

•6 NAD+

•2 FAD•2 ADP + 2 P

•Outputs:•4 CO2

•6 NADH•2 FADH2

•2 ATP

½ of the above per cycle

The Electron Transport Chain

• Involves a series of integral membrane proteins in the inner mitochondrial membrane capable of oxidation/reduction

• Each electron carrier is reduced as it picks up electrons and is oxidized as it gives up electrons

• Small amounts of energy is released in small steps

• Energy used to form ATP by chemiosmosis

Chemiosmosis • Small amounts of energy released as substances are passed along inner membrane

• Energy used to pump H+ ions from matrix into space between inner & outer membrane

• High concentration of H+ is maintained outside of inner membrane

• ATP synthesis occurs as H+ diffuses through a special H+ channel in inner membrane

Steps in Electron Transport

• Carriers of electron transport chain are clustered into 3 complexes that each act as proton pump (expel H+)

• Mobile shuttles pass electrons between complexes• Last complex passes its electrons (2H+) to a half of O2 molecule to

form a water molecule (H2O)

Proton Motive Force & Chemiosmosis

• Buildup of H+ outside the inner membrane creates + charge– electrochemical gradient potential energy is called proton motive force

• ATP synthase enzyme within H+ channel uses proton motive force to synthesize ATP from ADP and P

Energy yields from Glycolysis -TCA

• Glycolysis and the citric acid cycle accounts for four ATP.

• ETC accounts for 32 or 34 ATP, and the grand total of ATP is therefore 36 or 38 ATP.

• Cells differ as to the delivery of the electrons from NADH generated outside the mitochondria.

• If they are delivered by a shuttle mechanism to the start of the electron transport system, 6 ATP result; otherwise, 4 ATP result.

• Most ATP is produced by the electron transport system and chemiosmosis.

• Per glucose molecule, ten NADH and two FADH2 take electrons to the electron transport system; three ATP are formed per NADH and two ATP per FADH2.

• Electrons carried by NADH produced during glycolysis are shuttled to the electron transport chain by an organic molecule.

Figure 25.7

A Summary of the Energy Yield of Aerobic Metabolism

04/12/23GKM/NSB 211: DIGESTIVE SYSTEM NUTRITION AND METABOLISM/2013

Thank you for listening !!

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