Fumarate

A citric acid cycle intermediate between succinate and malate. Raised fumarate can indicate that the next step, conversion to malate by fumarase, is running more slowly.

What fumarate does in the body

Fumarate is formed in the citric acid cycle when succinate dehydrogenase – complex II of the respiratory chain – oxidises succinate; the electrons released go to coenzyme Q10. The enzyme fumarase then adds water to fumarate, forming malate. Fumarate is also produced outside the citric acid cycle: in the urea cycle, with which the liver disposes of nitrogen from protein breakdown, in the breakdown of the amino acids phenylalanine and tyrosine, and in building the purine components of DNA. A fumarase in the cytoplasm also converts this fumarate into malate, which enters the mitochondria and returns there to energy metabolism.

Low fumarate – what happens in the body?

Little fumarate is formed when the citric acid cycle runs more slowly before succinate dehydrogenase or the enzyme itself is slowed – for example with a lack of vitamin B2 or with damaged iron-sulphur centres; succinate then tends to rise while fumarate stays low, and complex II supplies fewer electrons to the respiratory chain. The value is also low when fumarate is processed into malate promptly. A low value is meaningful mainly in relation to succinate and malate.

High fumarate – what happens in the body?

A raised value shows that fumarate is being formed faster than fumarase can convert it into malate. The rest of the citric acid cycle then receives less supply: less malate and oxaloacetate are formed, less NADH reaches the respiratory chain and the cell produces less ATP. Accumulated fumarate also reacts with proteins and with glutathione (succination) and can thereby alter their function. Raised values occur with acquired disorders of the mitochondria, with increased fumarate from the urea cycle and amino acid breakdown – for example with high protein turnover – and rarely with inherited disorders of fumarase.

The interpretation is given in your report.