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| {{MitoPedia
| | #REDIRECT [[Electron-transfer-pathway state]] |
| |description=[[File:SUITp-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.
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| 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 FADH<sub>2</sub>-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.
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| 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 FADH<sub>2</sub> is the ''product'' of SDH. In contrast, FADH<sub>2</sub> is the ''substrate'' of [[electron transferring flavoprotein]] (CETF).
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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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| {{MitoPedia concepts
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| |mitopedia concept=MitoFit Quality Control System
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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
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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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