Succinate (succinic acid)

A citric acid cycle intermediate, substrate of succinate dehydrogenase (complex II of the respiratory chain). Raised with mitochondrial dysfunction and inflammation.

What succinate does in the body

Succinate is formed in the citric acid cycle from succinyl-CoA; in this step the cell directly produces an energy-rich molecule (GTP or ATP). Succinate dehydrogenase, which converts succinate into fumarate, has a special position: it is also complex II of the respiratory chain and passes the electrons via its cofactor FAD (from vitamin B2) and iron-sulphur centres directly to coenzyme Q10. Succinate thus links the citric acid cycle directly with the respiratory chain. Outside the mitochondria, succinate acts as a signal: via the receptor SUCNR1 and by stabilising the low-oxygen factor HIF-1α, it stimulates immune cells to produce inflammatory messengers.

Low succinate – what happens in the body?

A low value usually shows that succinate is processed promptly and succinate dehydrogenase is working well. Less succinate is also formed when the preceding steps run more slowly – for example when alpha-ketoglutarate dehydrogenase is slowed by a lack of vitamin B1 or other B vitamins – or when succinyl-CoA is increasingly diverted to other pathways, for example to make haem, the pigment component of haemoglobin. The respiratory chain then also receives fewer electrons via complex II.

High succinate – what happens in the body?

When succinate builds up, it is being formed faster than succinate dehydrogenase can convert it. The enzyme needs vitamin B2 and intact iron-sulphur centres and passes its electrons to coenzyme Q10 – if one of these components is lacking or the respiratory chain is overloaded by a lack of oxygen, succinate is broken down more slowly. When oxygen is lacking, the enzyme can even work in the reverse direction, so that succinate accumulates further. Accumulated succinate passes from the cells into the blood and stimulates inflammatory reactions via SUCNR1 and HIF-1α; when oxygen returns, it is oxidised rapidly, and more reactive oxygen compounds are produced in the respiratory chain in the process. Raised values have been observed in studies with inflammation, after intense exertion and with disorders of the respiratory chain; gut bacteria also produce succinate.

The interpretation is given in your report.