La protección ambiental y la distribución de la renta

The respiratory chain (RC) is composed of five key enzyme complexes (I-V) that are imbedded within the inner membrane (Hatefi 1985). Electrons are donated from NADH and FADH2 and flow through the complexes. As mentioned previously, NADH is

generated in the matrix and electron transport in the respiratory chain begins with reoxidizing NADH by removing a hydride ion (2 electrons) to regenerate NAD+ (Equation 1.28).

These two electrons are passed to the first of many electron carriers in the RC. They start with very high energy, which is gradually lost as the electrons are passed along the chain

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(Alberts, Johnson et al. 2008). Essentially, the electrons pass along metal ions bound to proteins, altering the electron affinity of the metal ions. The proteins are grouped into the RC enzyme complexes that are held in the inner mitochondrial membrane by transmembrane proteins. The complexes have increasing levels of affinity for electrons, which are passed along each complex until they are transferred to oxygen, which has the highest affinity. This complicated process of electron transfer exists in cells in order to avoid the huge free-energy drop of simply transferring the electrons from NADH directly to molecular oxygen (O2), in which the majority of the energy would be released as heat

(Alberts, Johnson et al. 2008). Instead, cells manage to store approximately half of the energy that is released by utilizing the electron transport chain (ETC).

It is important to briefly define some of the other proteins and enzymes that are involved in the RC. Flavoproteins are a polypeptide that contains a flavin adenosine dinucleotide (FAD) or a flavin mononucleotide (FMN) prosthetic group. Flavoproteins can accept or donate electrons as pairs (Equation 1.29-1.30) (Karp 2008). Cytochromes are proteins that contain bound heme groups and only facilitate one-electron transfers. They accomplish this by changing the oxidation state of their iron atom from Fe3+ to Fe2+ when accepting an electron (Karp 2008). There are other iron-sulfur proteins that can carry electrons, and like cytochrome, participate in one-electron transfer. Usually, these contain either two or four iron atoms bound to an equal number of sulfur atoms and to cysteine side-chains. Another important component is Coenzyme Q (CoQ), quinone (Q), or ubiquinone (uq), which is is a small, soluble electron carrier within the lipid bilayer of the

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inner membrane (Equation 1.31). Bound to these respiratory chain proteins are flavins, and two copper atoms that also carry electrons.

Table 1-2 Electron transfer in mitochondria Equations 𝐻> _{→ 𝐻}I_{+ 2𝑒}> _(1.28) 𝐹𝐴𝐷 + 2𝑒>_{+ 2𝐻}I _{→ 𝐹𝐴𝐷𝐻} 0 (1.29) 𝐹𝑀𝑁 + 2𝑒>_{+ 2𝐻}I _{→ 𝐹𝑀𝑁𝐻} 0 (1.30) 𝑄 + 2𝑒>_{+ 2𝐻}I _{→ 𝑄𝐻} 0 (1.31) 2𝑂₀>_{∙ +2𝐻}I _{→ 𝐻} 0𝑂0+ 𝑂0 (1.32) 𝐻₀𝑂₀+ 𝐹𝑒0I_{→ 𝐹𝑒}bI_{+ 𝑂𝐻 ∙ +𝑂𝐻}> _(1.33)

The individual complexes contain several electron carriers (Table 1-3) (Karp 2008).

1. Complex I, known as NADH dehydrogenase (or NADH-coenzyme Q reductase)

is the largest complex, containing over 45 polypeptides (Guenebaut, Schlitt et al. 1998). It accepts two electrons from NADH, making it the first link between the products of the TCA cycle / fatty acid oxidation and the respiratory chain. Within Complex I, electrons flow from: NADHà FMNà iron-sulfur centersà

ubiquinoneà cytochrome bc1 complex. The end result is the net transport of protons from the matrix to the intermembrane space, generating a proton-motive force (Grivennikova, Kapustin et al. 2001).

2. Complex II, known as succinate dehydrogenase (or succinate-coenzyme Q

reductase) (SDH) provides another direct link to the TCA cycle, as it is the only enzyme of the TCA cycle that is also an integral membrane protein. Here, succinate binds and a hydride is transferred to FAD, resulting in electron transfer to iron-sulfur centers before a final transfer to 2 electrons to CoQ: succinate + CoQ à Fumarate + CoQH2. Unlike complex 1, there is no proton-motive force

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generated due to the small free energy of the reaction, and only ~1.5ATP are generated per FADH2, contrasted with the 2.5ATP per NADH (Cecchini 2003).

3. Complex III, or coenzyme Q reductase, transfers electrons from CoQH2

generated either by Complex I or Complex II to reduce cytochrome c. Complex III functions as a dimer and utilizes a pathway known as the Q-cycle. Briefly, CoQH2 binds to the Q site, and then one electron is transferred to an iron-sulfur

protein, and then to cytochrome c1. This allows 2 protons to be released into the intermembrane space. The second electron is transferred to a heme, generating CoQ, which can diffuse from the Q site. This process occurs twice within to complete a Q-cycle, with a net result of two electrons transported to cytochrome c1, and finally to cytochrome c (Karp 2008).

4. Complex IV, or cytochrome c reductase, transfers electrons, one at a time, from

cytochrome c, which are passed (four at a time) to reduce molecular oxygen into water. This is a key point: that the cell can use O2 for respiration because this

complex holds onto molecular oxygen at a special bimetallic center until it picks up four electrons, and can be safely released while avoiding the generation of superoxide radicals (𝑂₀>_{∙). This reaction accounts for ~90% of total oxygen}

uptake in most cells, and is vital for aerobic respiration (Alberts, Johnson et al. 2008).

5. Complex V or ATP synthase is composed of two principle sectors, F1 and F0. It

has a ring of six subunits that project out onto the matrix side of the inner membrane. This ring is held in place by an “arm” that connects it to a group of

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transmembrane proteins that form a “stator” within the membrane. This piece is in contact with the “rotor”—a ring of 10-14 transmembrane protein subunits (Abrahams, Leslie et al. 1994).

Table 1-3 Properties of the components of the mitochondrial respiratory chain Complex Mass (kD) # subunits Substrate binding _{site sides} Electron _carriers

I 850 46 NADH (matrix) _{CoQ (lipid) Iron-sulfur} FMN

II 140 4 Succinate (matrix) _{CoQ (lipid) Iron-sulfur} FAD

III 248 11 Cyt c (intermembrane) CoQ (lipid) Iron-sulfur Heme IV 162 13 O2 (matrix) Cyt c (intermembrane) Heme Copper

Cytochrome c 13 1 Cyt c1,a Heme