Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways

Table 3

Control distribution of oxidative phosphorylation.

Enzyme	𝐶^JATP𝑣𝑖	Rat organ mitochondria	Specific inhibitor	Inhibition mechanism	Reference
NADH-CoQ-oxidoreductase (Site 1 of energy conservation or Complex I of respiratory chain)	0.15	Heart (0.5 mM pyr + 0.2 𝜇M Ca^2+)	Rotenone	Noncompetitive tightly bound	[93]
	0.26	Heart (10 mM pyr + 10 mM mal)			[95]
	0.31	Kidney (0.5 mM pyr + 0.2 𝜇M Ca^2+)			[93]
	0.06	Kidney (10 mM pyr + 10 mM mal)			[95]
	0.06–0.10	Brain (0.05 mM pyr + 0.4 𝜇M Ca^2+)			[91]
	0.25	Brain (10 mM pyr + 10 mM mal)			[95]
	0	Tumor (10 mM glut + 3 mM mal)			[96]
	0.27	Liver (10 mM pyr + 10 mM mal)			[95]
	0.13	Skeletal muscle (10 mM pyr + 10 mM mal)			[95]
CoQ.cytochrome c oxidoreductase (Site 2 of energy conservation or Complex III of respiratory chain)	0.01	Heart	Antimycin	Noncompetitive tightly bound	[93]
	0.19	Heart			[95]
	0.02	Kidney			[95]
	0.05–0.11	Brain			[91]
	0.02	Brain			[95]
	0	Tumor			[96]
	0.43	Liver (5 mM Succ + 1 𝜇M Ca^2+)			[94]
	0.07	Liver			[95]
	0.22	Skeletal muscle			[95]
Cytochrome c oxidase (Site 3 of energy conservation or Complex IV of respiratory chain)	0.11	Heart	Cyanide or azide	Noncompetitive simple	[93]
	0.13	Heart			[95]
	0.04	Kidney			[95]
	0.02–0.07	Brain			[91]
	0.02	Brain			[95]
	0.04	Tumor			[96]
	0.23	Liver			[94]
	0.03	Liver			[95]
	0.20	Skeletal muscle			[95]
ATP/ADP transporter (adenine-nucleotides or ATP/ADP transporter, carrier or exchanger)	0.24	Heart	Carboxy-atractyloside (CAT)	Noncompetitive tightly bound	[93]
	0.04	Heart			[95]
	0	Kidney			[93]
	0.07	Kidney			[95]
	0.08	Brain			[91]
	0.08	Brain			[95]
	0.60–0.70	Tumor			[96]
	0.48	Liver			[93]
	0.01	Liver			[93]
	0.37	Skeletal muscle (10 mM Glut + 3 mM mal)			[97]
	0.08	Skeletal muscle			[95]
ATP synthase	0.34	Heart	Oligomycin	Noncompetitive tightly bound	[93]
	0.12	Heart			[95]
	0.32	Kidney			[93]
	0.27	Kidney			[95]
	0.09–0.20	Brain			[91]
	0.26	Brain			[95]
	0.28	Tumor			[96]
	0.05	Liver			[94]
	0.20	Liver			[95]
	0.10	Skeletal muscle			[97]
	0.10	Skeletal muscle			[95]
Pi transporter	0.15	Heart	Mersalyl	Noncompetitive simple	[93]
	0.14	Heart			[95]
	0.43	Kidney			[93]
	0.28	Kidney			[95]
	0.13	Brain			[91]
	0.26	Brain			[95]
	0	Tumor			[96]
	0.05–0.12	Liver			[94]
	0.26	Liver			[95]
	0.15	Skeletal muscle			[97]
	0.08	Skeletal muscle			[95]
Pyruvate transporter	0.15	Heart	α-cyano-4-hydroxy-cinnamate	Noncompetitive simple	[95]
	0.03	Kidney			[95]
	0.08	Brain			[91]
	0.26	Brain			[95]
	0.21	Liver			[95]
	0.20	Skeletal muscle			[95]
Dicarboxylates transporter	0.05–0.14	Liver	Malate or butyl-malonate	Competitive simple	[94]
External ATPase	0.40	Skeletal muscle	Purified ATPase addition		[94]