ATP in mitochondria

The mechanism of active transport is of fundamental importance in biology. As we shall see in Chapter 19, the formation of ATP in mitochondria and chloroplasts occurs by a mechanism that is essentially ATP-driven ion transport operating in reverse. The energy made available by the spontaneous flow of protons across a membrane is calculable from Equation 11-3 remember that AG for flow down an electrochemical gradient has a negative value, and AG for transport of ions against an electrochemical gradient has a positive value. 

This reaction is fully reversible, so after the intense demand for ATP ends, the enzyme can recycle AMP by converting it to ADP, which can then be phosphorylated to ATP in mitochondria A similar enzyme, guanylate kinase, converts GMP to GDP at the expense of ATP. By pathways such as these, energy conserved in the catabolic production of ATP is used to supply the cell with all required NTPs and dNTPs. 

During the 1940s, when it had become clear that formation of ATP in mitochondria was coupled to electron transport, the first attempts to pick the system apart and understand the molecular mechanism began. This effort led to the identification and at least partial characterization of several flavoproteins, iron-sulfur centers, ubiquinones, and cytochromes, most of which have been described in Chapters 15 and 16. It also led to the picture of mitochondrial electron transport shown in Fig. 10-5 and which has been drawn in a modem form in Fig. 18-5. 

C. Fatty acids cross the inner mitochondrial membrane on a carnitine carrier. This process is inhibited during fatty acid synthesis by malonyl CoA. Fatty acids are very insoluble in water and are transported in the blood by serum albumin. They cross the plasma membrane and are converted to fatty acyl CoA by CoASH and ATP. In the process, ATP is converted to AMP, so fatty acid activation utilizes the equivalent of 2 ATP. In mitochondria, fatty acids are oxidized to C02 and H20. They cannot be oxidized in red blood cells, which lack mitochondria. 

Mitochondrial oxidative phosphorylation is the process by which ATP is synthesized in mitochondria during the passage of electrons along a chain of carriers. Chemical and chemiosmotic theories for this process have been propounded by their respective adherents, and mechanisms in bioenergetics have been reviewed, but experimental evidence to support these theories has been difficult to obtain with living systems. However, this year, reduced lipoic acid and unsaturated fatty acids have been shown to function as cofactors in the energy-linked synthesis of ATP in mitochondria, and this observation has prompted much activity in this field which will be discussed more fully in Section 6 of this Chapter. 

Energy transfer between mitochondria and the myofibrillar ATPases is mediated by phosphocreatine (Chapter 17). The phosphocreatine shuttle is illustrated schematically in Figure 21-13. Synthesis of ATP in mitochondria is closely coupled to that of phosphocreatine. Since the reaction... 

The anaerobic phosphorylation of ADP to ATP in mitochondria offers an excellent site for chemotherapeutic attack. The uncoupling of oxidative phosphorylation would lead to inhibition of ATP synthesis and subsequent starvation of the worms. A number of uncouplers of oxidative phosphorylation are now known, the first being 2,4-dinitrophenol (9) described by Loomis and Lipmann in 1948 [44]. Niclosamide (10) and other salicylanilide anthelmintics have been found to inhibit an-... 

There are many ways to seriously disrupt our biological machine. Carbon monoxide binds to hemoglobin and prevents oxygen from getting to our cells. Cyanide shuts down the production of ATP in mitochondria. Hemlock is a weed that contains a mixture of at least eight rather toxic molecules that target the nervous system. Thallium ions (TH) are particularly toxic because they are highly water soluble and once in the body they bind to ion channels and disrupt other processes that normally function with potassium ions (K" "). 

---