Succinate dehydrogenase

Ribbon model of complex II (from chicken according to PDB  1YQ3 ) in the membrane with the subunits SdhA (green), SdhB (cyan), SdhC (magenta) and SdhD (yellow).

Scheme of electron transport in complex II

The enzyme succinate dehydrogenase (SDH), more precisely succinate: ubiquinone oxidoreductase (systematic name), also called complex II , is an enzyme complex consisting of four subunits. It is the only membrane-bound protein of the citric acid cycle and, as complex II of the respiratory chain, is directly integrated into the electron transport chain of the inner mitochondrial membrane. The enzyme catalyzes

the oxidation of succinate to fumarate with FAD as oxidant :

+   FAD   + FAD H ₂ ${\displaystyle \rightleftharpoons }$

the simultaneous transport of two electrons across the membrane boundary :

2e ^- (inside) + FAD H ₂     2e ^- (outside) + FAD + 2H ⁺ ${\displaystyle \rightleftharpoons }$

with the help of these electrons the reduction of ubiquinone ( coenzyme Q ) to ubiquinol ( EC  1.3.5.1 ):

Q + 2H ⁺ + 2e ^-   Q H ₂ ${\displaystyle \rightleftharpoons }$  

Mutations in one of the four coding genes can be responsible for hereditary metabolic diseases in humans (see table).

structure

Ribbon model of complex II, the cofactors as spherical caps from top to bottom: heme, ubiquinone (pink), 3Fe4S, 4Fe4S, 2Fe2S, FAD (red) with substrate succinate (black).

In humans, the protein consists of four protein subunits (see table).

gene	protein	Amino acids	UniProt	OMIM	comment
SDHA	Flavoprotein subunit	621	P31040	600857	Complex II deficiency
SDHB	Iron-sulfur protein subunit	252	P21912	185470	Pheochromocytoma , paraganglioma , Carney-Stratakis syndrome
SDHC	Cytochrome b560 subunit	140	Q99643	602413	4 isoforms; Paraganglioma , Carney Stratakis Syndrome
SDHD	Cytochrome b560 subunit	103	O14521	602960	Pheochromocytoma , paraganglioma , Carney-Stratakis syndrome , Leigh syndrome, and colorectal cancer

In evolutionary terms , the flavoprotein is the oldest subunit and homologous proteins can therefore already be found in many bacteria ( EC  1.3.99.1 ). With the evolution of the eukaryotes, the iron-sulfur protein was added, and with the vertebrates and the then added cytochrome, the complex was anchored in the membrane.

function

The enzyme catalyzes the oxidation of succinate to fumarate and the reduction of ubiquinone ( coenzyme Q ) to ubiquinol. In contrast to NADH , the FADH ₂ that is produced as a hydrogen carrier during this oxidation in the citric acid cycle does not occur freely, but is bound as a prosthetic group to the SdhA subunit of the enzyme complex. Its reoxidation takes place through a chain of one-electron transfers starting with the three iron-sulfur clusters Fe ₂ S ₂ , Fe ₄ S ₄ , Fe ₃ S _{4 of} the SdhB subunit, up to cytochrome b ₅₆₀ (in mitochondria) or cytochrome b ₅₅₆ ( in bacteria) of the subunits SdhC and SdhD. This ultimately reduces the quinoid - i.e. oxidized - form of coenzyme Q (ubiquinone) into the phenolic form, ubiquinol.

Since the iron complexes involved are only capable of one-electron transfers , the reoxidation of FADH ₂ to FAD or the reduction of ubiquinone, which each provide or require two electrons, takes place in two stages via radical , but stable, semichinoid intermediate stages . The binding pocket for succinate is in the subunit SdhA; that for ubiquinone is formed by the three subunits SdhB, SdhC and SdhD. Due to its lipophilic polyisoprenyl chain , ubiquinone / ubiquinol is membrane- soluble. It therefore serves as a mobile electron carrier from complex II to complex III of the respiratory chain.

The succinate dehydrogenase redox chain :

The balance of this step of the citric acid cycle results in a transfer of two electrons from succinate to ubiquinone. However, this enzyme does not transport protons.

Inhibitor

• Malonate

Individual evidence

1. ↑ UniProt P31040
2. ↑ UniProt P21912
3. ↑ UniProt Q99643
4. ↑ UniProt O14521
5. ↑ Fumarate reductase / succinate dehydrogenase FAD-binding site

See also

• Citric acid cycle
• Respiratory chain

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Citric Acid Cycle  - Learning and Teaching Materials

• Video: succinate dehydrogenase . Institute for Scientific Film (IWF) 2005, made available by the Technical Information Library (TIB), doi : 10.3203 / IWF / C-12757 .