Cellular Respiration

Review
Cellular respiration is the first major topic for which you apply your knowledge of chemistry. For the most part, however, the chemistry is descriptivethat is, you wont have to solve chemical equations or even memorize structural formulas. Instead, you need to provide names of major molecules, describe their sequence in a metabolic process, and most importantly, describe how the process accomplishes its metabolic objective. Cellular respiration is an extremely important topic; free-response questions about respiration frequently appear on the AP exam. Cellular respiration is an ATP-generating process that occurs within cells. Energy is extracted from energy-rich glucose to form ATP from ADP and Pi. The chemical equation describing this process is C6H12O6 + 6 O2

C6H12O6 is glucose. Sometimes, you see CH2O or (CH2O)n. These are general formulas for glucose or any carbohydrate. Cellular respiration in the presence of O2 is called aerobic respiration. Aerobic respiration is divided into three components: glycolysis, the Krebs cycle, and oxidative phosphorylation. Refer to Figure 4-1 as you read the following descriptions of the metabolic processes.

Glycolysis
Glycolysis is the decomposition (lysis) of glucose (glyco) to pyruvate (or pyruvic acid). Nine intermediate products are formed, and, of course, each one is catalyzed by an enzyme. In six of the steps, magnesium ions (Mg2+) are cofactors that promote enzyme activity. The steps are summarized here and in Figure 4-1. 1. 2 ATP are added. The first several steps require the input of energy. This changes glucose in preparation for subsequent steps. 2. 2 NADH are produced. NADH, a coenzyme, forms when NAD+ combines with two energy-rich electrons and H+ (obtained from an intermediate molecule during the breakdown of glucose). As a result, NADH is an energyrich molecule. 3. 4 ATP are produced. 4. 2 pyruvate are formed. In summary, glycolysis takes 1 glucose and turns it into 2 pyruvate, 2 NADH, and a net of 2 ATP (made 4 ATP, but used 2 ATP). The process occurs in the cytosol.

The Krebs Cycle

The Krebs cycle details what happens to pyruvate, the end product of glycolysis. Although the Krebs cycle is described for 1 pyruvate, remember that glycolysis produces 2 pyruvate. In Figure 4-1, the 2 next to the pyruvate and the Krebs cycle is a reminder to multiply the products of this cycle by 2 to account for the products of a single glucose. 1. Pyruvate to acetyl CoA. In a step leading up to the actual Krebs cycle, pyruvate combines with coenzyme A (CoA) to produce acetyl CoA. In that reaction, 1 NADH and 1 CO2 are also produced. 2. Krebs Cycle: 3 NADH, 1 FADH2, 1 ATP, CO2. The Krebs cycle begins when acetyl CoA combines with OAA (oxaloacetate) to form citrate. There are seven intermediate products. Along the way, 3 NADH and 1 FADH2 are made, and CO2 is released. FADH2, like NADH, is a coenzyme, accepting electrons during a reaction. Because the first product made from acetyl CoA is the 3-carbon citrate (citric acid), the Krebs cycle is also known as the citric acid cycle or the tricarboxylic acid (TCA) cycle. The CO2 produced by the Krebs cycle is the CO2 animals exhale when they breathe.

6 CO2 + 6 H2O + energy

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glucos e glucos e 2 ATP 2 ADP

2 P GAL

2 NAD+ 2 NADH
4 ADP 4 ATP

GLYCOLYS IS 2 pyruvate
4

ATP

AEROBIC PATHWAY

ANAEROBIC PATHWAYS alcohol fermentation lactic acid fermentation 2 pyruvate 2 NADH 2 NAD+ 2 lactate

pyruvate (x2) CO2 NAD+ NADH acetyl CoA OAA 2 CO2 ATP ADP
FADH 2 FAD

2 pyruvate 2 CO2 2 acetaldehyde

citrate

2 NADH 2 NAD+ 2 ethanol

CO2

KREBS CYCLE (x2) 3NAD+ 3 NADH

ATP NADH NAD+ + H + + 2e -

FADH 2

FAD + 2H + + 2e -

electron ADP transpot ATP chain ADP OXIDATIVE PHOS PHORYLATION ATP 2e 2H+ + O2 H2O

ADP ATP

ATP

O2

H2O

Respiration

Figure 4-1

Oxidative Phosphorylation
Oxidative phosphorylation is the process of extracting ATP from NADH and FADH2. Electrons from NADH and FADH2 pass along an electron transport chain. The chain consists of proteins that pass these electrons from one carrier protein to the next. Some carrier proteins, such as the cytochromes, include nonprotein parts containing iron. Along each step of the chain, the electrons give up energy used to phosphorylate ADP to ATP. NADH provides electrons that have enough energy to generate about 3 ATP, while FADH2 generates about 2 ATP.

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The final electron acceptor of the electron transport chain is oxygen. The 12 O2 accepts the two electrons and, together with 2 H+, forms water. One of the carrier proteins in the electron transport chain, cytochrome c, is so ubiquitous among living organisms that the approximately 100-amino-acid sequence of the protein is often compared among species to assess genetic relatedness.

How Many ATP?

How many ATP can theoretically be made from the energy released from the breakdown of 1 glucose? In the cytoplasm, 1 glucose molecule produces 2 NADH, 2 ATP, and 2 pyruvate during glycolysis. When the 2 pyruvate (from 1 glucose) are converted to 2 acetyl CoA, 2 more NADH are produced. From 2 acetyl CoA, the Krebs cycle produces 6 NADH, 2 FADH2, and 2 ATP. If each NADH produces 3 ATP during oxidative phosphorylation, and FADH2 produces 2 ATP, the total ATP count from 1 original glucose appears to be 38. However, this number is reduced to 36 because the 2 NADH that are produced in the cytoplasm during glycolysis must be transported into the mitochondria for oxidative phosphorylation. The transport of NADH across the mitochondrial membrane reduces the net yield of each NADH to only 2 ATP (Table 4-1). However, the total yield from 1 glucose actually hovers around 30 ATP due to variations in mitochondria efficiencies and competing biochemical processes.

Table 4-1
Source glycolysis glycolysis pyruvate to acetyl CoA Krebs cycle Krebs cycle Krebs cycle Total 2 FADH2 6 NADH = = 2 NADH 2 NADH = = FADH2 Produced NADH Produced ATP Yield 2 ATP 4 ATP 6 ATP 2 ATP 18 ATP 4 ATP 36 ATP

A balance sheet accounting for ATP production from glucose by aerobic respiration. Total ATP production is theoretically 36 ATP for each glucose processed.

Mitochondria
The two major processes of aerobic respiration, the Krebs cycle and oxidative phosphorylation, occur in mitochondria. There are four distinct areas of a mitochondrion, as follows (Figure 4-2). 1. Outer membrane. This membrane, like the plasma membrane, consists of a double layer of phospholipids. 2. Intermembrane space. This is the narrow area between the inner and outer membranes. H+ ions (protons) accumulate here. 3. Inner membrane. This second membrane, also a double phospholipid bilayer, has convolutions called cristae (singular, crista). Oxidative phosphorylation occurs here. Within the membrane and its cristae, the electron transport chain, consisting of a series of protein complexes, removes electrons from NADH and FADH2 and transports H+ ions from the matrix to the intermembrane space. Some of these protein complexes are indicated in Figure 4-2 (PC I, PC II, PC III, and PC IV). Another protein complex, ATP synthase, is responsible for the phosphorylation of ADP to form ATP. 4. Matrix. The matrix is the fluid material that fills the area inside the inner membrane. The Krebs cycle and the conversion of pyruvate to acetyl CoA occur here.

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outer membrane intermembrane space inner membrane crista matrix

Mitochondrion

outer membrane intermembrane space

H+ H+ H+ H+ protein complexes

H+ H+

H+ H+

H+ H+ H+

H+ H+ H+ H+

H+ 4A

H+ H+

H+

PC I inner membrane 3A H+ NADH matrix 2A NAD+ 2e -

PC II 2e -

PC III

ATP synthase

PC IV 2e -

FADH 2 2B

FAD

3B H+

H+ 3C

ADP + P i H+

4B H+ + O2 H2O

ATP 5

1 FADH2 NADH ATP CO2 K r e b s c y c l e FAD NAD+ ADP + P i

Chemiosmosis in Mitochondria

Figure 4-2

Chemiosmosis in Mitochondria
Chemiosmosis is the mechanism of ATP generation that occurs when energy is stored in the form of a proton concentration gradient across a membrane. A description of the process during oxidative phosphorylation in mitochondria follows (Figure 4-2). 1. The Krebs cycle produces NADH and FADH2 in the matrix. In addition, CO2 is generated and substrate-level phosphorylation occurs to produce ATP. 2. Electrons are removed from NADH and FADH2. Protein complexes in the inner membrane remove electrons from these two molecules (2A, 2B). The electrons move along the electron transport chain, from one protein complex to the next (shown as a shaded strip within the inner membrane).

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3. H+ ions (protons) are transported from the matrix to the intermembrane compartment. Protein complexes transport H+ ions from the matrix, across the inner membrane, and to the intermembrane space (3A, 3B, 3C). 4. A pH and electrical gradient across the inner membrane is created. As H+ are transferred from the matrix to the intermembrane space, the concentration of H+ increases (pH decreases) in the intermembrane space (4A) and decreases in the matrix (pH increases). The concentration of H+ in the matrix decreases further as electrons at the end of the electron transport chain (PC IV) combine with H+ and oxygen to form water (4B). The result is a proton gradient (equivalent to a pH gradient) and an electric charge (or voltage) gradient. These gradients are potential energy reserves in the same manner as water behind a dam is stored energy. 5. ATP synthase generates ATP. ATP synthase, a channel protein in the inner membrane, allows the protons in the intermembrane compartment to flow back into the matrix. The protons moving through the channel generate the energy for ATP synthase to generate ATP. It is similar to how turbines in a dam generate electricity when water flows through them.

Two Types of Phosphorylation

Two metabolic processes for generating ATP occur. 1. Substrate level phosphorylation occurs when a phosphate group and its associated energy is transferred to ADP to form ATP. The substrate molecule (the molecule with the phosphate group) donates the high energy phosphate group. Such phosphorylation occurs during glycolysis. 2. Oxidative phosphorylation occurs when a phosphate group is added to ADP to form ATP, but the energy for the bond does not accompany the phosphate group. Instead, electrons in the electron transport chain of oxidative phosphorylation supply the energy. That energy is used to generate the H+ gradient which, in turn, supplies the energy to ATP synthases to generate ATP from ADP and a phosphate group.

Anaerobic Respiration
What if oxygen is not present? If oxygen is not present, no electron acceptor exists to accept the electrons at the end of the electron transport chain. If this occurs, then NADH accumulates. After all the NAD+ has been converted to NADH, the Krebs cycle and glycolysis both stop (both need NAD+ to accept electrons). When this happens, no new ATP is produced, and the cell soon dies. Anaerobic respiration is a method cells use to escape this fate. Two common metabolic pathways, alcohol and lactic acid fermentation, are slightly different, but the objective of both processes is to replenish NAD+ so that glycolysis can proceed once again. Anaerobic respiration occurs in the cytosol alongside glycolysis.

Alcohol Fermentation
Alcohol fermentation (or sometimes, just fermentation) occurs in plants, fungi (such as yeasts), and bacteria. The steps, illustrated in Figure 4-1, are as follows: 1. Pyruvate to acetaldehyde. For each pyruvate, 1 CO2 and 1 acetaldehyde are produced. The CO2 formed is the source of carbonation in fermented drinks like beer and champagne. 2. Acetaldehyde to ethanol. The important part of this step is that the energy in NADH is used to drive this reaction, releasing NAD+. For each acetaldehyde, 1 ethanol is made and 1 NAD+ is produced. The ethanol (ethyl alcohol) produced here is the source of alcohol in beer and wine. It is important that you recognize the objective of this pathway. At first glance, you should wonder why the energy in an energy-rich molecule like NADH is removed and put into the formation of ethanol, essentially a waste product that eventually kills the yeast (and other organisms) that produce it. The goal of this pathway, however, does not really concern ethanol, but the task of freeing NAD+ to allow glycolysis to continue. Recall that in the absence of O2, all the NAD+ is bottled up in NADH. This is because oxidative phosphorylation cannot accept the electrons of NADH without oxygen. The purpose of the fermentation pathway, then, is to release some NAD+ for use by glycolysis. The reward for this effort is 2 ATP from glycolysis for each 2 converted pyruvate. This is not much, but its better than the alternative0 ATP.

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Lactic Acid Fermentation

Only one step occurs in lactic acid fermentation (Figure 4-1). A pyruvate is converted to lactate (or lactic acid) and in the process, NADH gives up its electrons to form NAD+. As in alcohol fermentation, the NAD+ can now be used for glycolysis. In humans and other mammals, most lactate is transported to the liver where it is converted back to glucose when surplus ATP is available.

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