Download
1 / 25
E N D
Conversion of Amino Acids toSpecialized Products M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.
Conversion of Amino Acids toSpecialized Products Heme purines pyrimidines hormones neurotransmitters biologically active peptides
Compounds related to histidine Decarboxylation of histidine forms histamine. Other compounds arising from histidine are shown here (beta-alanine is derived from cytosine) Derived from beta-alanine and histidine Anserine is formed by methylation of carnosine by S-adenosylmethione Carnosine and anserine occur in muscle and activate myosin ATPase activity (myosin is the chief enyzme involved in contraction of muscle) Homocarnosine occurs in the brain. Homocarnosinosis is an extremely rare disorder due to carnosinase deficiency. It is associated with mental retardation
Structures of natural polyamines Spermidine and spermine function in diverse physiologic processes that share as a common thread a close relationship to cell proliferation and growth. The fact that they are polycations allows these compounds to bind to DNA and RNA and they are involved in packaging of DNA in bacteriophages.
Biosynthesis of spermidine and spermine Addition of inhibitors of ornithine decarboxylase, the enzyme that catalyzes the initial reaction in polyamine biosynthesis, triggers overproduction of ornithine decarboxylase. (hence, the machinery that makes the protein is regulated tightly in order that a supply of the precursors to spermidine and spermine is always available). Ornithine decarboxylase has a half-life of 10 minutes.
tryptophan Biosynthesis andmetabolism ofmelatonin Tyrosine hydroxylase Melatonin regulates circadian rhythms Serotonin is a potent vasoconstrictor and stimulator of smooth muscle contraction Inhibition of MAO by iproniazid increases effects of serotonin
Eumelanin and pheomelanin biosynthesis Melanin polymers contain both eumelanin and pheomelanin in varying amounts. Albinism accompanies defective melanin biosynthesis. Tyrosine hydroxylase-negative albinos lack all visual pigment
Biosynthesis of creatine and creatinine Creatine is a high-energy storage compound in muscle. ATP is made from creatine phosphate by creatine kinase
Porphyrins Porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of various porphyrins. Examples of important porphyrins in nature are the iron porphyrins such as the heme of hemoglobin, and the magnesium porphyrin in chlorophyll.
Conversion of porphobilinogen to uroporphyrinogens Usually, type III is formed but in certain porphyrias, the type I isomers are formed in excess. These compounds are not conjugated due to the methylene groups. Oxidation is catalyzed by light leading to formation of the colored porphyrins.
Absorption spectrum of hematoporphyrin Porphyrins have a very strong absorbance due to extended conjugation of double bonds. Porphyrins are used in cancer phototherapy. Tumors often take up more porphyrins than normal tissue. Lasers will excite the porphyrin to a high energy intermediate that breaks down and resleases cytotoxic agents that kill the tumor. Accumulation of porphyrinogens can cause sensitivity to light leading to skin damages
Intermediates, enzymes, and regulation of heme synthesis Mutations in in enzymes 2- 8 cause the porphyrias. Regulation of heme synthesis occurs at ALA synthase by a repression-derepression mechanism mediated by heme. The dotted lines indicate the negative regulation by repression.
Biochemical causes of the major signs and symptoms of the porphyrias
