BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

                                              Highlights of Vosoritide Program - Vosoritide is the FDA approved drug for the treatment of Achondroplasia  - Developed by Biomarin, and received orphan designation from FDA and EMA - New Drug Application Under Review by FDA with Set PDUFA August 2020 - EMA validated the marketing authorization application - Publication of positive outcome data from Phase 3 study in Lancet Achondroplasia is   the most common form of disproportionate short stature in humans, it is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face, and base of the skull.  This condition is caused by a mutation in the fibroblast growth factor receptor 3 gene (FGFR3), a negative regulator of bone growth. Beyond disproportionate short stature...

  Metabolic Pathway for Phenylalanine and Tyrosine  ( For MCQ Practice click here ) Conversion of Phenylalanine to Tyrosine  - Phenylalanine hydroxylase (PAH) converts phenylalanine to tyrosine  - PAH is encoded by the PAH gene located in Chromosome 12 and consist of 13 exons  - Tetrameters with each monomer consisting of the catalytic site, regulator site, and subunit binding domain  - Phenylalanine hydroxylase is tetrahydrobiopterin (BH4) requiring enzyme  - Dihydrobioteridine reductase catalyzes the conversion of dihydrobiopteridine to tetrahydrobiopterin  - Deficiency of enzyme caused phenylketonuria  Figure- Overview of Phenylalanine and Tyrosine Metabolism   Transamination of Tyrosine  - Tyrosine aminotransferase catalyzes the conversion to tyrosine to p-hydroxyphenylpyruvate  - Tyrosine aminotransferase is a Pyridoxal-5-phosphate requiring enzyme  - In the process, alpha-ketoglutarate is converted into glutama...

Hemoglobin Gene Structure and Arrangement The human hemoglobins are encoded in two tightly linked structures: Alpha Gene Family:  - Alpha gene cluster is encoded by genes located in chromosome 16 - The alpha gene cluster contains  zeta gene that is expressed in the embryonic stage,  the alpha-like genes that are not expressed (pseudogenes) Alpha genes that encode the alpha subunit of hemoglobin Beta Gene Family - The gene for the beta-globin chain is located on chromosome 11 - The beta gene cluster consists of  the beta gene encodes for beta-subunit of adult hemoglobin two gamma genes (G γ  and A γ ) that encode the γ chain of fetal hemoglobin the delta gene that codes for the subunit present in HbA2   Expression of Hemoglobin During Various Developmental Stages Embryonic Hemoglobin:  Red blood cells first appear about six weeks after conception, these RBCs contain the embryonic hemoglobin synthesized by the yolk sac. These include Hb Portland ( ζ 2 γ ...