Lecture 20:  Cell Metabolism -Respiration pdf _download pdf _download

pdf download   video w/o sound

Electron Transport Chain -Movie   ATP synthase -Movie

 

 

 

C6H12O6 + 6 O2 ---> 6 CO2 + 6 H2O + energy (heat and light).

 

Under anaerobic conditions some cells continue glycolysis and produce a limited amount of ATP by the process fermentation.

For these cells there is a NET GAIN of TWO ATP's per glucose molecule -as long as they can recycle the reducing power of NAD+ through fermentation.

aa

This form of anaerobic respiration produces incompletely broken down carbon skeletons such as lactic acid and alcohol

    

In the ABSENCE of oxygen the reduced form of NAD+ (NADH + H+) builds up and becomes a cellular toxin....

It therefore needs to be RECYCLED.....

Hence the formation of a reduced carbon intermediat : LACTIC ACID build up in muscle tissue -feel the burn.

 

In the PRESENCE of oxygen, however, the reduced form of NAD+ (NADH + H+) can be converted back into the oxidized form ......

 

NAD+ + 2e- + H+   ---->  NADH

 

....and just like the normal reaction this is an "explosive" ENERGY yielding reaction... with almost the same energy yield.

 

H2 +  1/2 O2  --->H2O

 

Pyruvate Oxidation -Dehydrogenase.   In this reaction, the 3 carbon pyruvate is converted to a 2-carbon Acetyl group attached to a Coenzyme A configuration.  A molecule of NADH + H+ is generated during this reaction.

 

      

 

Summary:

 

Glucose (6 carbon) ---> Pyruvate (3 carbon)                                     Net yield = 1 ATP and 1 NADH + H+

                                     ---> Pyruvate (3 carbon)                                     Net yield = 1 ATP and 1 NADH + H+

Pyruvate (3 carbon) ---> Acetyl CoA (2 carbon) + CO2                       Net yield = 1 NADH + H+          

Pyruvate (3 carbon) ---> Acetyl CoA (2 carbon) + CO2                       Net yield = 1 NADH + H+          

 

Acetyl~ CoA (2 carbon) + Oxaloacetate (4 carbon)    ----->    Oxaloacetate (4 carbon) + 2 CO2                

                                                                                                                      Net yield = 1 ATP,  1 FADH2and  3NADH + H+

 

Acetyl~ CoA (2 carbon) + Oxaloacetate (4 carbon)    ----->    Oxaloacetate (4 carbon) + 2 CO2                

                                                                                                                      Net yield = 1 ATP,  1 FADH2and  3NADH + H+

 

 

Total Net yield = 4 ATP,   2 FADH2&nbsp and  10 NADH + H+

 

The question now is, how exactly does the cell make use of all these hydrogens that are interacting with the various hydrogen carriers?  It passes them on to the....

If the reaction

 

Respiratory Chain:

 

in eukaryotes the respiratory chain of proteins, along with the TCA (Citric Acid) cycle enzymes, are normally found in the mitochondria.

in prokaryotes (that are able to respire aerobically)- the chain is found in the .....inner cell membrane.

 

  

 

The respiratory chain, which is simply a series of proteins embedded within the membrane of mitochondria (or the cytoplasmic membrane of prokaryotes), is the final component of complete glucose oxidation, and is needed to make full use of the generated reducing agents and the energy they possess.

Remember, it all boils down to two things.

(a) those "Redox reactions" that we reviewed in the last lecture.......

A gain of one or more electrons or hydrogen atoms is called reduction.

The loss of one or more electrons or hydrogen atoms is called oxidation.

Whenever one material is reduced, another is oxidized.

 

                  

 

(b) the maintenance of a H+gradient, coupled to an "energy turbine", that is placed (in Eukaryotes) in the mitochondrial membranes.

If the complete oxidation of NADH + H+ is allowed to proceed in short, decremental steps....

 

 

...wherein a protein is reduced by NADH + H+ and the attached electrons- required to balance the charge of the reactants_followed by another protien being reduced by this newly oxidised protein......then, not only can the NAD+ of glycolysis and the citric acid cycle be "recycled", but the process can be repeated until more and more H+ 's can be exchanged from "carriers" within and the potential energy of the whole reaction can be harnessed and used to create ATP.

 

 

 

 

NADH + H+ + 1/2 O2  ---->  NAD+ H2O

 

In this way electrons pass along a series of membrane-associated electron carriers called the respiratory chain.

The flow of electrons by way of a series of redox reactions causes the active transport of protons across the inner mitochondrial membrane and into the intermembrane space, creating a concentration gradient of H+ 's.

If these protons are then allowed to diffuse -through specific proton channels- back into the cell, down their concentration- (and electrical-) gradients, back into the matrix of the mitochondrion, then ATP can be created in the process through a  special ATP generating turbine system.

 

 

 

Nobel Prize 1997

The entire process of ATP synthesis by electron transport through the respiratory chain is called oxidative phosphorylation.

Thus, the respiratory chain transports electrons out of the and releases energy

NADH + H+ passes its hydrogen atoms to the NADH-Q reductase protein complex. The NADH-Q reductase passes the hydrogens on to ubiquinone(Q) forming QH2.

The QH2 passes electrons to cytochrome c reductase, which in turn passes them to cytochrome c. Next to receive them is cytochrome c oxidase. The cytochrome oxidase passes them on to oxygen.

Reduced oxygen unites with two hydrogens to form water.

FADH2can also enter the chain through succinate-Q reductase.

As electrons pass through the respiratory chain, the associate protons are continuously pumped into the intermembrane space against a concentration and electrical gradient

The potential energy generated by this gradient of Protons is called the proton-motive force.

The subsequent movement of these proton (down their gradient, through the ATPase pump/cchannel causes the physical rotation of the core of the enzyme, which pushes the ADP and Pi so close together that they bond.

The synthesized ATP is transported out of the mitochondrial matrix almost as quickly as it is made, and is now available to the cell.

 

Contrasting Energy Yield:

A total net of 38 ATP molecules can be generated from each glucose molecule in glycolysis followed by complete aerobic respiration.

The inner mitochondrial membranes of most mitochondria are impermeable to NADH. To get into the matrix requires the energy of one ATP for each of the two NADH2+ produced per molecule of glucose. This reduces the net yield somewhat.

In contrast, fermentation has a net yield of only 2 ATP molecules from each glucose molecule.

The end products of fermentation (such as lactic acid and ethanol) contain much more unused energy than the end products of aerobic respiration.

In aerobic respiration, each NADH + H+ generates three ATP molecules, and each FADH2 generates two ATP molecules when consumed in the electron transport chain.

Coupled with glycolysis, aerobic respiration captures ~ 63 percent of the energy stored in glucose; fermentation captures only ~ 3.5 percent. Consequently, Aerobic respiration is 18 times more efficient at harvesting energy from glucose.

Metabolic Pathways.... It is no accident

 

Glucose utilization pathways can yield more than just energy. They are interchanges for diverse biochemical traffic.

Intermediate chemicals are generated that are substrates for the synthesis of lipids, amino acids, nucleic acids, and other biological molecules.

 

Catabolism and anabolism involve interconversions using "carbon skeletons"

 

  

 

Catabolic uses of molecules include the following:

Polysaccharides are hydrolyzed into sugars, which pass on to glycolysis.
Lipids are converted to fatty acids, which become acetate (and then acetyl CoA), and glycerol, which is converted to dihydroxyacetone phosphate, an intermediate in glycolysis.

Proteins are hydrolyzed into amino acids, which feed into glycolysis or the citric acid cycle.

Anabolic interconversions include the following:
Gluconeogenesis is the process by which intermediates of glycolysis and the citric acid cycle are used to form glucose.
Acetyl CoA can form fatty acids. Amino acids can be polymerized into proteins.
Common fatty acids have even numbers of carbons because they are formed by adding two-carbon acetyl CoA units.

The citric acid cycle intermediate alpha-ketoglutarate is the starting point for the synthesis of purines. Oxaloacetate is a starting point for pyrimidines.

In this way, catabolism and anabolism are integrated

The levels of the products and substrates of energy metabolism are remarkably constant.

Cells regulate the enzymes of catabolism and anabolism to maintain a balance.

What happens if inadequate fuel molecules are available?

Polysaccharides are an intermediate storage form of energy. A typical person has about one day's worth of energy stored as the carbohydrate glycogen.

A typical person has about a week of needed amino acids stored as protein, and over a month's energy stored as fats.

Fats are compact energy storage molecules because they exclude water and are particularly hydrocarbon rich.

If food is withheld, glycogen is used up first, then fats. As fats are depleted, in humans this leads to a build up of ketones in the body, which develops into a condition called ketosis which elicits a mild euphoric state, and dulls the senses....as in a diabetic shock.

Fats cannot cross the blood-brain barrier. To supply glucose to the brain, glucose must be synthesized by gluconeogenesis (which is a reversal of glycolysis). This requires the use of amino acids.

After fats are depleted, proteins alone provide the energy.

At this point, however, in humans the important disease-fighting proteins (antibodies) are also consumed, and the likeliness of severe illness increases.