Question

B. The electron transport chain (ETC) consists of four protein complexes as shown in the following figure.

1. Name the complex(es) where electrons enter the ETC:

2. How many electrons are accepted at the entry point(s) per cycle?

Complex Complex 111 Complex IV Complex 11 I K АТР Synthase

The Electron Transport Chain showing the four complexes embedded in the inner mitochondrial membrane. Barbiturates inhibits Complex I and cyanide inhibits Complex IV.

3. Barbiturates, a class of drugs, interrupt the flow of electrons in the chain by inhibiting Complex I. Cyanide, a dangerous poison, inhibits Complex IV. Given what you know about the ETC, explain why cyanide can be deadly while barbiturates are less dangerous.

Answer 1

1.

Name the complex(es) where electrons enter the ETC:-

• Complex l
• Complex lll
• Complex lv

2.

How many electrons are accepted at the entry point(s) per cycle :-

Complex l :-

The start of the reaction, and indeed of the entire electron chain, is the binding of a NADH molecule to complex I and the donation of two electrons. The electrons enter complex I via a prosthetic group attached to the complex, flavin mononucleotide (FMN). The addition of electrons to FMN converts it to its reduced form, FMNH2. The electrons are then transferred through a series of iron–sulfur clusters: the second kind of prosthetic group present in the complex.There are both [2Fe–2S] and [4Fe–4S] iron–sulfur clusters in complex I.

Complex ll :-

It is unusual because it is the only enzyme that is part of both the citric acid cycle and the electron transport chain. Complex II consists of four protein subunits and contains a bound flavin adenine dinucleotide (FAD) cofactor, iron–sulfur clusters, and a heme group that does not participate in electron transfer to coenzyme Q, but is believed to be important in decreasing production of reactive oxygen species. It oxidizes succinate to fumarate and reduces ubiquinone. As this reaction releases less energy than the oxidation of NADH, complex II does not transport protons across the membrane and does not contribute to the proton gradient.

Complex lll :-

As only one of the electrons can be transferred from the QH2 donor to a cytochrome c acceptor at a time, the reaction mechanism of complex III is more elaborate than those of the other respiratory complexes, and occurs in two steps called the Q cycle. In the first step, the enzyme binds three substrates, first, QH2, which is then oxidized, with one electron being passed to the second substrate, cytochrome c. The two protons released from QH2 pass into the intermembrane space. The third substrate is Q, which accepts the second electron from the QH2 and is reduced to Q.−, which is the ubisemiquinone free radical. The first two substrates are released, but this ubisemiquinone intermediate remains bound. In the second step, a second molecule of QH2 is bound and again passes its first electron to a cytochrome c acceptor. The second electron is passed to the bound ubisemiquinone, reducing it to QH2 as it gains two protons from the mitochondrial matrix. This QH2 is then released from the enzyme.

As coenzyme Q is reduced to ubiquinol on the inner side of the membrane and oxidized to ubiquinone on the other, a net transfer of protons across the membrane occurs, adding to the proton gradient. The rather complex two-step mechanism by which this occurs is important, as it increases the efficiency of proton transfer. If, instead of the Q cycle, one molecule of QH2 were used to directly reduce two molecules of cytochrome c, the efficiency would be halved, with only one proton transferred per cytochrome c reduced.

Complex lv :-

This enzyme mediates the final reaction in the electron transport chain and transfers electrons to oxygen and hydrogen (protons), while pumping protons across the membrane.

3.

why cyanide can be deadly while barbiturates are less dangerous :-

Amytal, a barbiturate, a plant product used as insecticide and pesticide, block the ETC between NADH dehydrogenase (Complex I) and CoQ. Consequently, they prevent the utilization of NADH as a substrate. On the contrary, electron flow resulting from the oxidation of Complex II is not affected, because these electrons enter through QH2, beyond the block.

The effect of Amytal has been observed in vitro, since the intoxication with amytal and other barbiturates in vivo affect mainly the CNS by acting on GABA-sensitive ion channels, an effect not related to the action of Amytal on Complex I.

On the contrary, in cyanide intoxication the inhibition of the respiratory chain has a primary role. Intoxication by cyanide can be seen relatively frequent in patients with smoke inhalation from residential or industrial fires. Also in persons related professionally with cyanide or derivatives in certain industries. Intentional poisoning can be seen in suicidal persons with access to cyanide compounds.

Cyanide affects practically all metalloenzymes, but its principal toxicity derives from the binding to the Fe+++ in the Hem groups in cytochrome Oxidase, inhibiting the functioning of the Electron Transport Chain. As a consequence, redox reactions in the respiratory chain will stop, energy will not be released, proton pumps will not function, so they will not return through Complex V, and the production of ATP will cease.

So, cyanide can be deadly while barbiturates are less dangerous.

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