<P> The causes of shift to right can be remembered using the mnemonic, "CADET, face Right!" for CO, Acid, 2, 3 - DPG, Exercise and Temperature . Factors that move the oxygen dissociation curve to the right are those physiological states where tissues need more oxygen . For example, during exercise, muscles have a higher metabolic rate, and consequently need more oxygen, produce more carbon dioxide and lactic acid, and their temperature rises . </P> <P> A decrease in pH (increase in H ion concentration) shifts the standard curve to the right, while an increase shifts it to the left . This occurs because at greater H ion concentration, various amino acid residues, such as Histidine 146 exist predominantly in their protonated form allowing them to form ion pairs that stabilize deoxyhemoglobin in the T state . The T state has a lower affinity for oxygen than the R state, so with increased acidity, the hemoglobin binds less O for a given P (and more H). This is known as the Bohr effect . A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH is called the root effect . This is seen in bony fish . The binding affinity of hemoglobin to O is greatest under a relatively high pH . </P> <P> Carbon dioxide affects the curve in two ways . First, CO accumulation causes carbamino compounds to be generated through chemical interactions, which bind to hemoglobin forming carbaminohemoglobin . CO is considered an Allosteric regulation as the inhibition happens not at the binding site of hemoglobin . Second, it influences intracellular pH due to formation of bicarbonate ion . Formation of carbaminohemoglobin stabilizes T state hemoglobin by formation of ion pairs . Only about 5--10% of the total CO content of blood is transported as carbamino compounds, whereas (80--90%) is transported as bicarbonate ions and a small amount is dissolved in the plasma. The formation of a bicarbonate ion will release a proton into the plasma, increasing acidity which also shifts the curve to the right as discussed above; low CO levels in the blood stream results in a high pH, and thus provides more optimal binding conditions for hemoglobin and O . This is a physiologically favored mechanism, since hemoglobin will drop off more oxygen as the concentration of carbon dioxide increases dramatically where tissue respiration is happening rapidly and oxygen is in need . </P> <P> 2, 3 - Bisphosphoglycerate or 2, 3 - BPG (formerly named 2, 3 - diphosphoglycerate or 2, 3 - DPG) is an organophosphate formed in erythrocytes during glycolysis and is the conjugate base of 2, 3 - bisphosphoglyceric acid . The production of 2, 3 - BPG is likely an important adaptive mechanism, because the production increases for several conditions in the presence of diminished peripheral tissue O availability, such as hypoxaemia, chronic lung disease, anaemia, and congestive heart failure, among others . High levels of 2, 3 - BPG shift the curve to the right (as in childhood), while low levels of 2, 3 - BPG cause a leftward shift, seen in states such as septic shock, and hypophosphataemia . In the absence of 2, 3 - BPG, hemoglobin's affinity for oxygen increases . 2, 3 - BPG acts as a heteroallosteric effector of hemoglobin, lowering hemoglobin's affinity for oxygen by binding preferentially to deoxyhemoglobin . An increased concentration of BPG in red blood cells favours formation of the T, low - affinity state of hemoglobin and so the oxygen - binding curve will shift to the right . </P>

Which of the following can shift the hemoglobin-oxygen dissociation curve to the right