Haldane effect
Encyclopedia
The Haldane effect is a property of hemoglobin
first described by the Scottish
physician
John Scott Haldane. Deoxygenation of the blood increases its ability to carry carbon dioxide; this property is the Haldane effect. Conversely, oxygenated blood has a reduced capacity for carbon dioxide.
compounds. Amino groups are available for binding at the N-terminals and at side-chains of arginine
and lysine
residues in hemoglobin. This forms carbaminohemoglobin
. Carbaminohemoglobin is the major contributor to the Haldane effect.
residues in hemoglobin can accept protons and act as buffers
. Reduced (deoxygenated) hemoglobin is a better proton acceptor
than the oxygenated form.
In red blood cells, the enzyme carbonic anhydrase
catalyzes the conversion of dissolved carbon dioxide to carbonic acid
, which rapidly dissociates to bicarbonate
and a free proton
:
CO2 + H2O → H2CO3 → H+ + HCO3-
By Le Chatelier's principle
, anything that stabilizes the proton produced will cause the reaction to shift to the right, thus the enhanced affinity of deoxyhemoglobin for protons enhances synthesis of bicarbonate and accordingly increases capacity of deoxygenated blood for carbon dioxide. The majority of carbon dioxide in the blood is in the form of bicarbonate. Only a very small amount is actually dissolved as carbon dioxide, and the remaining amount of carbon dioxide is bound to hemoglobin.
In addition to enhancing removal of carbon dioxide from oxygen-consuming tissues, the Haldane effect promotes dissociation of carbon dioxide
from hemoglobin in the presence of oxygen
. In the oxygen-rich capillaries of the lung, this property causes the displacement of carbon dioxide to plasma as low-oxygen blood enters the alveolus and is vital for alveolar gas exchange.
The general equation for the Haldane Effect is:
H+ + HbO2 ←→ H+Hb + O2; however, this equation is confusing as it reflects primarily the Bohr effect
. The significance of this equation lies in realizing that oxygenation of Hb promotes dissociation of H+ from Hb, which shifts the bicarbonate buffer equilibrium towards CO2 formation; therefore, CO2 is released from RBCs.
This partially explains the observation that some patients with emphysema
might have an increase in PaCO2 (partial pressure of arterial dissolved carbon dioxide) following administration of supplemental oxygen even if content of CO2 stays equal.
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
first described by the Scottish
Scottish people
The Scottish people , or Scots, are a nation and ethnic group native to Scotland. Historically they emerged from an amalgamation of the Picts and Gaels, incorporating neighbouring Britons to the south as well as invading Germanic peoples such as the Anglo-Saxons and the Norse.In modern use,...
physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
John Scott Haldane. Deoxygenation of the blood increases its ability to carry carbon dioxide; this property is the Haldane effect. Conversely, oxygenated blood has a reduced capacity for carbon dioxide.
Carbamino
Carbon dioxide can bind to amino groups, creating carbaminoCarbamino
Carbamino refers to a compound composed by the addition of carbon dioxide with a free amino group in an amino acid or a protein, such as hemoglobin forming carbaminohemoglobin....
compounds. Amino groups are available for binding at the N-terminals and at side-chains of arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
and lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
residues in hemoglobin. This forms carbaminohemoglobin
Carbaminohemoglobin
Carbaminohemoglobin is a compound of hemoglobin and carbon dioxide, and is one of the forms in which carbon dioxide exists in the blood. When carbon dioxide binds to hemoglobin, carbaminohemoglobin is formed, lowering hemoglobin's affinity for oxygen via the Haldane effect...
. Carbaminohemoglobin is the major contributor to the Haldane effect.
Buffering
HistidineHistidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
residues in hemoglobin can accept protons and act as buffers
Buffering agent
A buffering agent is a weak acid or base used to maintain the acidity of a solution at a chosen value. The function of a buffering agent is to prevent a rapid change in pH when acids or bases are added to the solution. Buffering agents have variable properties—some are more soluble than others;...
. Reduced (deoxygenated) hemoglobin is a better proton acceptor
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
than the oxygenated form.
In red blood cells, the enzyme carbonic anhydrase
Carbonic anhydrase
The carbonic anhydrases form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons , a reversible reaction that occurs rather slowly in the absence of a catalyst...
catalyzes the conversion of dissolved carbon dioxide to carbonic acid
Carbonic acid
Carbonic acid is the inorganic compound with the formula H2CO3 . It is also a name sometimes given to solutions of carbon dioxide in water, because such solutions contain small amounts of H2CO3. Carbonic acid forms two kinds of salts, the carbonates and the bicarbonates...
, which rapidly dissociates to bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
and a free proton
Proton
The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....
:
CO2 + H2O → H2CO3 → H+ + HCO3-
By Le Chatelier's principle
Le Châtelier's principle
In chemistry, Le Chatelier's principle, also called the Chatelier's principle, can be used to predict the effect of a change in conditions on a chemical equilibrium. The principle is named after Henry Louis Le Chatelier and sometimes Karl Ferdinand Braun who discovered it independently...
, anything that stabilizes the proton produced will cause the reaction to shift to the right, thus the enhanced affinity of deoxyhemoglobin for protons enhances synthesis of bicarbonate and accordingly increases capacity of deoxygenated blood for carbon dioxide. The majority of carbon dioxide in the blood is in the form of bicarbonate. Only a very small amount is actually dissolved as carbon dioxide, and the remaining amount of carbon dioxide is bound to hemoglobin.
In addition to enhancing removal of carbon dioxide from oxygen-consuming tissues, the Haldane effect promotes dissociation of carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
from hemoglobin in the presence of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
. In the oxygen-rich capillaries of the lung, this property causes the displacement of carbon dioxide to plasma as low-oxygen blood enters the alveolus and is vital for alveolar gas exchange.
The general equation for the Haldane Effect is:
H+ + HbO2 ←→ H+Hb + O2; however, this equation is confusing as it reflects primarily the Bohr effect
Bohr effect
Bohr effect is a property of hemoglobin first described in 1904 by the Danish physiologist Christian Bohr , which states that an increasing concentration of protons and/or carbon dioxide will reduce the oxygen affinity of hemoglobin...
. The significance of this equation lies in realizing that oxygenation of Hb promotes dissociation of H+ from Hb, which shifts the bicarbonate buffer equilibrium towards CO2 formation; therefore, CO2 is released from RBCs.
Clinical significance
In patients with lung disease, lungs may not be able to increase alveolar ventilation in the face of increased amounts of dissolved CO2.This partially explains the observation that some patients with emphysema
Emphysema
Emphysema is a long-term, progressive disease of the lungs that primarily causes shortness of breath. In people with emphysema, the tissues necessary to support the physical shape and function of the lungs are destroyed. It is included in a group of diseases called chronic obstructive pulmonary...
might have an increase in PaCO2 (partial pressure of arterial dissolved carbon dioxide) following administration of supplemental oxygen even if content of CO2 stays equal.