Proton transport blood

The lactate and proton concentrations, and hence the pH in the blood, depend not only on the rate of release from muscle, and other tissues, but also on the rate of their removal from the blood. The transporter that transports lactate and protons out of cells also transports them into cells. There are two tissues that are important in then-removal from the blood liver and heart (Figure 6.8). 

Carbon dioxide is a major end product of aerobic metabolism. In complex organisms, this carbon dioxide is released into the blood and transported to the lungs for exhalation. While in the blood, carbon dioxide reacts with water. The product of this reaction is a moderately strong acid, carbonic acid (pAT = 3.5), which becomes bicarbonate ion on the loss of a proton. 

The enzyme carbonic anhydrase promotes the hydration of COg. Many of the protons formed upon ionization of carbonic acid are picked up by Hb as Og dissociates. The bicarbonate ions are transported with the blood back to the lungs. When Hb becomes oxygenated again in the lungs, H is released and reacts with HCO3 to re-form HgCOj, from which COg is liberated. The COg is then exhaled as a gas. 

Under some conditions, the rate of glycolysis from glycogen to lactate plus protons can be greater than the capacity of the transporter to transport all the lactate and protons out of the muscle. In this case, they accumulate in the muscle and the pH falls to about 6.5 or even lower (Chapter 13). This can occur, for example, when a muscle is working close to maximum, or when there is a poor blood supply to a working muscle. If this continued for any length of time, the increase in proton concentration could be sufficient to damage some of the proteins in the muscle. Indeed, if this decrease in pH occurred in the blood, it would be very serious and could rapidly lead to death. This is prevented in two ways ... 

Although the condition is hypothetical, it can be calculated that if all of the skeletal muscles in the body degraded glycogen to lactic acid at the maximum rate and, if aU of the protons that were produced were transported into the blood, it would exceed the buffering capacity of the blood and the pH would fall dramatically (see below). This could soon result in death. Hence the inhibitory effect of protons... 

Omeprazole (p. 167) can cause maximal inhibition of HCl secretion. Given orally in gastric juice-resistant capsules, it reaches parietal cells via the blood. In the acidic milieu of the mucosa, an active metabolite is formed and binds covalently to the ATP-driven proton pump (H+/K+ ATPase) that transports H+ in exchange for IC into the gastric juice. Lansoprazole and pantoprazole produce analogous effects. The proton pump inhibitors are first-line drugs for the treatment of gastroesophageal reflux disease. 

Urea (H2N-CO-NH2) is the diamide of carbonic acid. In contrast to ammonia, it is neutral and therefore relatively non-toxic. The reason for the lack of basicity is the molecule s mesomeric characteristics. The free electron pairs of the two nitrogen atoms are delocalized over the whole structure, and are therefore no longer able to bind protons. As a small, uncharged molecule, urea is able to cross biological membranes easily. In addition, it is easily transported in the blood and excreted in the urine. 

In the red blood cell this reaction plays an important role in COj transport from the tissues to the lungs. In the kidney, the protons of the H3O+ are exchanged for Na+ ions, which are reabsorbed, while HCO3 is decomposed through a shift of the equilibrium to the left. Carbonic anhydrase therefore plays a crucial role in maintaining the ion and water balance between the tissues and urine. 

Organic cation transporters OCT SLC22A2/3 Luminal Blood to endothelium Organic cation/proton exchange... 

Figure 20-4 Proposed function of ceruloplasmin copper (CpCu " ) as a proton (hydrogen ion) recipient from cellular ferrous iron.The resulting oxidation of Fe to the ferric state permits its binding and transport by plasma transferrin. CpCu" is oxidized (regenerated to CpCu ) by reaction with oxygen, oxidized thiol groups, or other oxidizing substances, (Modified from Johnson AM. Ceru/op/osm/n. In Ritchie RF, Navolotskaia 0, editors. Serum proteins in clinical medicine. Vol. I Laboratory section. Scarborough, ME Foundation for Blood Research, 1996 13.01-13.03.)...

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