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| {{MitoPedia
| | #REDIRECT [[Electron-transfer-pathway state]] |
| |description=[[File:SUIT-Catg NFSGpTm.jpg|right|400px]]
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| '''Substrate types''' in mitochondrial [[SUIT protocols]] are types of reduced substrates feeding electrons into the [[electron transfer system]] (ETS) at different levels of mitochondrial pathways. Distinction of substrate types on the basis of four mt-pathway types provides the rationale for defining [[categories of SUIT protocols]].
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| Substrates of '''type 4''' feed electrons into dehydrogenases and enzyme systems upstream of the type 3 pathway level. Electron transfer from type 4 substrates (N and F) converges at the NADH-junction and FADH<sub>2</sub>-junction (N- and F-junction). Representative '''type N substrates''' are pyruvate, glutamate and malate, and also citrate, oxoglutarate. The corresponding dehydrogenases ([[Pyruvate dehydrogenase |PDH]], [[Glutamate dehydrogenase |GDH]], [[Malate dehydrogenase |MDH]] and [[Malic enzyme |mtME]]; [[Isocitrate dehydrogenase |IDH]], [[Oxoglutarate dehydrogenase |OgDH]]) generate NADH, the substrate of [[Complex I]] (CI). '''Type F substrates''' are fatty acids involved in β-oxidation, generating (enzyme-bound) FADH<sub>2</sub>, the substrate of [[electron transferring flavoprotein]] (CETF). Succinate does not belong to the type 4 substrates, since FADH<sub>2</sub> is the ''product'' of CII, whereas FADH<sub>2</sub> is the ''substrate'' of CETF. 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.
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| Substrates of '''type 3''' (e.g. [[succinate]], [[glycerophosphate]]) feed electrons into respiratory complexes directly upstream of the [[Q-junction]]. Succinate is the substrate of [[succinate dehydrogenase]] (SDH, CII) localized on the inner side of the inner mt-membrane. [[Glycerophosphate]] is the substrate of [[glycerophosphate dehydrogenase complex]] (CGpDH) localized on the outer face of the inner mt-membrane. [[Choline]] is the type 3 substrate of [[choline dehydrogenase]].
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| Substrates of '''type 2''' feed electrons into Complex III (CIII) with further electron transfer downstream of the [[Q-junction]].
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| 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).
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| |info=[[Gnaiger 2014 MitoPathways]]
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| }}
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| {{MitoPedia concepts
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| |mitopedia concept=MitoFit Quality Control System
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| }}
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| {{MitoPedia methods}}
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| {{MitoPedia O2k and high-resolution respirometry
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| |mitopedia O2k and high-resolution respirometry=SUIT protocol, SUIT state
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| }}
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| {{MitoPedia topics
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| |mitopedia topic=Substrate and metabolite
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| }}
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| Contributed by [[Gnaiger E]] 2016-02-01, edited 2016-02-10
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| == Substrate types on different pathway levels ==
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| ::::* Substrate types on the pathway level of converging NADH- and FADH<sub>2</sub>-linked dehydrogenases, including the TCA cycle and beta-oxidation:
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| :::'''N:''' [[NADH]]-linked substrates ('CI-linked')
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| :::'''F:''' [[FADH2 |FADH<sub>2</sub>]]-linked substrates (FAO)
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| ::::* Substrate types on the pathway level of electron transfer complexes converging at the Q-junction:
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| :::'''S:''' [[Succinate]] ('CII-linked')
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| :::'''Gp:''' [[Glycerophosphate]] ('CGpDH-linked')
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| ::::* Substrate types on the single step level of cytochrome ''c'' oxidase (CIV), the terminal step in the aerobic electron transfer system:
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| :::'''Tm:''' Artificial electron transfer susbstrate [[TMPD]] (Tm) maintained in a reduced state by [[ascorbate]] (As) and reducing cytochrome ''c'' as the substrate of [[CIV]].
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