ETS pathway types

high-resolution terminology - matching measurements at high-resolution

ETS pathway types

Description

Substrate types in SUIT protocols are types of reduced substrates feeding electrons into the electron transfer system (ETS) at different levels of mitochondrial pathways.

Substrates of type 4 feed electrons into dehydrogenases and enzyme systems upstream of the type 3 pathway level. Succinate does not belong to the type 4 substrates. Electron transfer from type 4 substrates (N and F) converges at the NADH-junction and FADH₂-junction (N- and F-junction). Representative type N substrates are pyruvate, glutamate and malate, whereas type F substrates are fatty acids. Fatty acid oxidation (FAO) not only depends on electron transfer through the F-junction (which is typically rate-limiting) but simultaneously generates NADH and thus depends on N-junction throughput. Hence FAO can be inhibited completely by inhibition of Complex I (CI). In addition and independent of this source of NADH, the type N substrate malate is required as a co-substrate for FAO in mt-preparations, since accumulation of AcetylCo inhibits FAO in the absence of malate. Malate is oxidized in a reaction catalyzed by malate dehydrogenase to oxaloacetate (yielding NADH), which then stimulates the entry of AcetylCo into the TCA cycle catalyzed by citrate synthase.

Substrates of type 3 (e.g. succinate, glycerophosphate) feed electrons into respiratory complexes upstream of the Q-junction. Note that succinate is the substrate for succinate dehydrogenase (SDH), whereas FADH₂ is the product of SDH. In contrast, FADH₂ is the substrate of electron transferring flavoprotein (CETF).

Substrates of type 2 feed electrons into Complex III (CIII) with further electron transfer downstream of the Q-junction.

Substrates of type 1 may be artificial electron donors (e.g. TMPD, Tm) essentially bypassing the ETS and feeding electrons directly into the terminal electron acceptor, cytochrome c oxidase (CIV) or alternative oxidases (single enzymatic step).

MitoPedia concepts: "MitoFit Quality Control System" is not in the list (MiP concept, Respiratory state, Respiratory control ratio, SUIT concept, SUIT protocol, SUIT A, SUIT B, SUIT C, SUIT state, Recommended, ...) of allowed values for the "MitoPedia concept" property. MitoFit Quality Control System"MitoFit Quality Control System" is not in the list (Enzyme, Medium, Inhibitor, Substrate and metabolite, Uncoupler, Sample preparation, Permeabilization agent, EAGLE, MitoGlobal Organizations, MitoGlobal Centres, ...) of allowed values for the "MitoPedia topic" property.

MitoPedia O2k and high-resolution respirometry: "SUIT protocol" is not in the list (O2k hardware, DatLab, Oroboros QM, O2k-Open Support, O2k-Respirometry, O2k-FluoRespirometry) of allowed values for the "MitoPedia O2k and high-resolution respirometry" property. SUIT protocol"SUIT protocol" is not in the list (O2k hardware, DatLab, Oroboros QM, O2k-Open Support, O2k-Respirometry, O2k-FluoRespirometry) of allowed values for the "MitoPedia O2k and high-resolution respirometry" property.

MitoPedia topics: Substrate and metabolite

Contributed by Gnaiger E 2016-02-01, edited 2016-02-10

Substrate types on different pathway levels

Substrate types on the pathway level of converging NADH- and FADH₂-linked dehydrogenases, including the TCA cycle and beta-oxidation:

N: NADH-linked substrates ('CI-linked')

F: FADH₂-linked substrates (FAO)

Substrate types on the pathway level of electron transfer complexes converging at the Q-junction:

S: Succinate ('CII-linked')

Gp: Glycerophosphate ('CGpDH-linked')

Substrate types on the single step level of cytochrome c oxidase (CIV), the terminal step in the aerobic electron transfer system:

Tm: Artificial electron transfer susbstrate TMPD (Tm) maintained in a reduced state by ascorbate (As) and reducing cytochrome c as the substrate of CIV.