Glutamate-anaplerotic pathway control state

high-resolution terminology - matching measurements at high-resolution

Glutamate-anaplerotic pathway control state

Description

G: Glutamate is an anaplerotic NADH-linked type 4 substrate (N). When supplied as the sole fuel substrate in the glutamate pathway control state, G is transported by the electroneutral glutamate-/OH- exchanger, and is oxidised via mt-glutamate dehydrogenase in the mitochondrial matrix. The G-pathway plays an important role in glutaminolysis.

Abbreviation: G

Reference: Gnaiger 2014 MitoPathways - Chapter 3.3

MitoPedia concepts: SUIT state 

Communicated by Gnaiger E 2016-01-25, edited 2016-11-29.

G(L)

LEAK state (L) with G alone as substrate can be evaluated in the following SUIT protocol:

• SUIT-007

• DL-Protocol for permeabilized cells (pce): SUIT-007 O2 pce D030

G(P)

OXPHOS state (P) with G alone as substrate can be evaluated in the following SUIT protocol:

• SUIT-007

• DL-Protocol for permeabilized cells (pce): SUIT-007 O2 pce D030

G(E)

ET state (E) with G alone as substrate can be evaluated in the following SUIT protocol:

• SUIT-007

• DL-Protocol for permeabilized cells (pce): SUIT-007 O2 pce D030

Details

In human skeletal muscle mitochondria, OXPHOS capacity with glutamate alone (G_P) is 50% to 85% of respiration in the GM pathway control state (GM_P). Accumulation of fumarate inhibits succinate dehydrogenase and glutamate dehydrogenase.

Glutaminolysis: Glutamate derived from hydrolyzation of glutamine is an important aerobic substrate in cultured cells, supporting anaplerosis. Mitochondrial glutamate dehydrogenase is particularly active in astrocytes, preventing glutamate induced neurotoxicity.

Anaplerosis from malate: mtNAD-malic enzyme supports an anaplerotic pathway when carbohydrate is limiting.