Hemoglobin physiology

Heck, R. F., 711 Heme, and dioxygen. 895-897 Hemerythrin. 908 Hemoglobin physiology of, 900-902 structure of, 902-908 Hermann-Mauguin system. 

PLASMA PROTEINS ASSOCIATED WITH HEMOGLOBIN PHYSIOLOGY... 

The Bohr effect in hemoglobin physiology is associated with... 

Diphosphoglycerate (2,3-DPG) is an important mediator of hemoglobin physiology (see Chapter 7). It is synthesized from 1,3-diphosphoglycerate. The... 

The transition between the T and R states of hemoglobin is also deeply involved in the Bohr effect and cooperativity. Therefore stabilization of either of the two stmctures should diminish these effects, which have important physiologic consequences. The clinical consequences of stabilization are not known. 

In 1982 a study of the usefulness of DBBF in the production of a blood substitute was reported (99). A single modification achieved the dual goals of reduced oxygen affinity and restricted tetramer—dimer dissociation. This work was confirmed in 1987 (98). The product, called aa-hemoglobin, was formulated in Ringer s lactate. P q under physiologic conditions is 3.7 kPa (28.0 torr). Hill s parameter is 2.2, and the Bohr effect was reduced (100). Plasma retention was increased, and the product appeared to be less heterogeneous than some of the other derivatives under study. Its production was scaled up by Baxter Healthcare Corp., under contract to the U.S. Army. 

The Physiological Significance of Cooperative Binding of Oxygen by Hemoglobin... 

We can determine quantitatively the physiological significance of the sigmoid nature of the hemoglobin oxygen-binding curve, or, in other words, the biological importance of cooperativity. The equation... 

Toxicity. A 1% concn of the gas in air is lethal to rats in 1 hour, its effect being similar to C monoxide the LD50 in rats when injected intra-peritoneally is 8.2ml/kg (Ref 16). Earlier workers assumed that the toxicity of N trifluoride would be similar to H fluoride and that the latter would be formed by hydrolysis in body tissues (Ref 1). This has recently been shown to be erroneous, and that it is stable under physiological conds. The toxic effect is due to its ability to complex with the hemoglobin of the blood causing anoxia. This effect is reversible, and animals receiving a sublethal dose recover rapidly upon removal from contact with N trifluoride (Ref 14)... 

THE OXYGEN DISSOCIATION CURVES FOR MYOGLOBIN HEMOGLOBIN SUIT THEIR PHYSIOLOGIC ROLES... 

Figure 6-5. Developmental pattern of the quaternary structure of fetal and newborn hemoglobins. (Reproduced, with permission, from Ganong WF Review of Medical Physiology, 20th ed. McGraw-Flill, 2001.)...

Physiologic changes that accompany prolonged exposure to high altitude include an increase in the number of erythrocytes and in their concentrations of hemoglobin and of BPG. Elevated BPG lowers the affinity of HbA for O2 (decreases P50), which enhances release of O2 at the tissues. 

Under physiologic conditions in the human adult, 1—2 X 10 erythrocytes are destroyed per hour. Thus, in 1 day, a 70-kg human turns over approximately 6 g of hemoglobin. When hemoglobin is destroyed in the body, globin is degraded to its constiment amino acids, which are reused, and the iron of heme enters the iron pool, also for reuse. The iron-free porphyrin portion of heme is also degraded, mainly in the reticuloendothehal cells of the liver, spleen, and bone marrow. 

Figure 38-4. Examples of three types of missense mutations resulting in abnormal hemoglobin chains. The amino acid alterations and possible alterations in the respective codons are indicated. The hemoglobin Hikari p-chain mutation has apparently normal physiologic properties but is electrophoretically altered. Hemoglobin S has a p-chain mutation and partial function hemoglobin S binds oxygen but precipitates when deoxygenated. Hemoglobin M Boston, an a-chain mutation, permits the oxidation of the heme ferrous iron to the ferric state and so will not bind oxygen at all.

Under physiological conditions, transfer of Et3PAufrom hemoglobin to albumin has been observed. The transfer is direct and does not require a low-molecular weight thiol such as GSH as an intermediary and indicates that inter-protein transfer of gold can occur spontaneously. The rapid and efficient manner of establishing this equilibrium (for transauration ) could determine many ofthe effects of intracellular and extracellular chemistry of gold. 

Additionally, with chronic hypoxia, normal hemoglobin and hematocrit values may represent relative anemia.12 Increased red blood cell production is a physiologic response to hypoxia however, this response may be blunted in CF and may result in symptoms of anemia despite normal lab values. Abnormal bleeding may also be observed as a result of vitamin K malabsorption or antibiotic-associated depletion of gastrointestinal flora and vitamin K synthesis. 

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