Succinic and Reduced Diphosphopyridine Nucleotide Oxidase Systems of Ascaris Muscle

On the Mechanism of Oxidative Phosphorylation. VII. The Energy-Requiring Reduction of Pyridine Nucleotide by Succinate and the Energy-Yielding Oxidation of Reduced Pyridine Nucleotide by Fumarate*

“…Figure 4 shows that 0.4 jug of the inhibitor per mg protein, which gave nearly 100% inhibition of respiration, produced less than 15% inhibition in Reactions ( 1) and (2) in the identical ETPh preparation. In this connection, it is of interest to note that the fumarate-dependent oxidation of NADH observed in extracts of Ascaris (Kmetec and Bueding, 1961) and Mycobacterium avium (Kusunose and Kusunose, 1959) is reported to be insensitive to antimycin. The mode of action of antimycin on normal respiration is supposed to be the prevention of the oxidation of reduced cytochrome b by Ci (Chance and Williams, 1956).…”

Identification of enzymes that have helminth-specific active sites and are required for Rhodoquinone-dependent metabolism as targets for new anthelmintics

“…This often takes the form of a reverse in the direction of a reaction. The canonical example is that of Complex II which uses succinate as a substrate and generates fumarate as a product during aerobic conditions; in anaerobic conditions, it uses fumarate as a substrate and generates succinate as a product [ 92 , 113 ]. There is a similar reverse in reaction direction for ETFDH and as we showed in this paper, ETFDH is also critical for RQ-dependent metabolism.…”

“…Because mammalian hosts only make and use UQ whereas STHs must make and use both RQ and UQ to switch to RQ-dependent anaerobic metabolism in the low oxygen niches of their hosts, several of these enzymes have undergone critical residue changes that has allowed us to identify key targets for potential new classes of anthelmintics. The best characterised molecular change in STHs that is driven by the requirement to be able to use both UQ and RQ is that in the quinone binding pocket of Complex II, succinate dehydrogenase [20,90,92,113,143,144]. Amongst the multiple amino acid changes around the quinone-binding pocket of Complex II, we have previously showed that single residue mutations in this pocket can alter the ability of C. elegans to use RQ-dependent metabolism suggesting that these helminth-specific residues are likely critical for the docking of RQ [34].…”

“…There are 5 QDHs in animals that are linked to the mitochondrial ETC. These comprise Succinate dehydrogenase (also known as Complex II) [26,[91][92][93]; Electron-Transferring Flavoprotein (ETF) dehydrogenase [94][95][96]; Proline dehydrogenase [97][98][99]; Glycerol 3-phosphate dehydrogenase [100][101][102]; and Dihydroorotic acid dehydrogenase [103]. We note that there are other quinone-coupled enzymes in animals including sulphide:quinone oxidoreductase (sqrd-1 in C. elegans [104]) as well as orthologues of D-and L-hydroxyglutarate dehydrogenase [105-107] (D2HGDH and L2HGDH; F45D5.12 and Y45G12B.3 respectively).…”

Ascaris suum NAD-Malic Enzyme Is Activated by l-Malate and Fumarate Binding to Separate Allosteric Sites

“…One equivalent of malate is acted upon by fumarase to produce fumarate, and the second malate equivalent is acted upon by malic enzyme to produce pyruvate, CO 2 and NADH (1,(3)(4). The NADH produced from the malic enzyme reaction is utilized by a flavo-protein-linked succinate dehydrogenase that reduces fumarate to succinate (1,(5)(6)(7). Concomitant with the fumarate reduction is a site I phosphorylation of ADP to ATP, which is the major source of the anaerobic energy production for the worm.…”