Histidine

Glycine

REF: Harper 26^th e p. 271-275

Steps of porphyrin ring synthesis:

 Heme synthesis—note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)

Isoleucine

Histidine

FIGLU is an intermediate metabolite of histidine catabolism. It is excereted in urine in increased quantity where there is folic acid deficiency as folic acid is needed for further metabolism of FIGLU.

Remember that a buffer is most effective when its pKa is within the pH range of the surrounding medium.

Histidine is the only amino acid with good buffering capacity at physiologic pH.

The imidazole side chain of histidine has a pKa around 6.0 and can reversibly donate and accept protons at physiologic pH.
 

Histidine has dissociaion constant close to physiologic pH of 7.4

The Beta-chain of Hb begins with valine and histidine. Both these amino acids are important in the synthesis and structure of heamoglobin.

 Alignment according to helical designation makes homology evident:

Residue F8 is the proximal heme-linked histidine, and the histidine on the distal side of the heme is E7. 

The iron atom is linked by a coordinate bond to the imidazole nitrogen (N) of histidine F8.

The E7 distal histidine, on the other side of the heme plane, is not bonded to the iron atom but is very close to the ligand-binding site.

Ref: Natarajan K., Townes T.M., Kutlar A. (2010). Chapter 48. Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities. In J.T. Prchal, K. Kaushansky, M.A. Lichtman, T.J. Kipps, U. Seligsohn (Eds), Williams Hematology, 8e

Serine provides the thioethanol moiety of coenzyme A, not Threonine. Because acetyl-CoA has a much higher energy content than acetic acid, it combines readily with substances in reactions that would otherwise require outside energy.

Acetyl-CoA is therefore often called “active acetate.”

pKa of histidine is 6.5 – 7.4. It allows for maximum buffering capacity at neutral pH.

Histamine is derived from the decarboxylation of the aminoacid histidine, a reaction catalyzed by the enzyme L-histidine decarboxylase present in the liver. It is a hydrophilic vasoactive amine.

Ref: Neuroscience in Medicine edited by P. Michael Conn, Page 496

Proteins can be effective buffers of body and intracellular fluids. Buffering capacity is dependent upon the presence of amino acids having ionizable side chains with pKs near physiological pH. In the example given, only histidine has an ionizable imidazolium group that has a pK close to neutrality (pK = 6.0).

Valine and leucine are amino acids with uncharged, branched side chains.

Lysine has a very basic amino group (pK = 10.5) on its aliphatic side chain that is positively charged at physiologic pH, and aspartic acid has a side chain carboxyl (pK = 3.8) that is negative at pH 7.

The pK value of imidazolium group of Histidine is 6.1 and therefore effective as a buffer at the physiological pH of 7.4. The buffering capacity of plasma proteins and hemoglobin is mainly due to histidine residue.

• In folic acid deficiency, transfer of the formimino group is impaired, and Figlu is excreted. 
• Excretion of Figlu following a dose of histidine thus can be used to detect folic acid deficiency.

Hemoglobin is the major intracellular buffer of blood which is present in erythrocytes.

Heamoglobin has 4 polypeptide chains, two identical a- chains and two identical p chains.

Iron (Fe²⁺) of Hb is bound to histidine & four pyrrole rings.

Heme is a derivative of porphyrin (protoporphyrin) porphyrin is composed by fusion of four pyrrole ring linked by methenyl (=CH) bridges, i.e. tetrapyrrole ring. Since an atom of iron is present, heme is a ferroprotoporphyrin. Four methyl, two vinyl and two propionate side chain groups are attached to the porphyrin ring. The iron is held in the center of porphyrin ring in ferrous form (Fe⁺²). Iron has six coordinated bonds: (i) four bonds are formed between the iron and nitrogen atoms of the porphyrin ring system; (ii) fifth bond is formed between nitrogen atoms of histidine residue of globin chain, known as proximal histidine (His F8); (iii) sixth bond is formed with oxygen.

The oxygenated form of hemoglobin is stabilized by the hydrogen bond between oxygen and side chain of another histidine residue of globin chain, known as distal histidine (His E7).