Title: Conversion of Amino Acids to Specialized Products
1Conversion of Amino Acids toSpecialized Products
Heme purines pyrimidines hormones neurotransmitter
s biologically active peptides
2Formation of glycine conjugates
3Compounds 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. Homocarnosinosi
s is an extremely rare disorder due to
carnosinase deficiency. It is associated
with mental retardation
4Arginine, ornithine, and proline metabolism
5Structures 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.
6Biosynthesis 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.
7Catabolism of polyamines
8Biosynthesis andmetabolism ofmelatonin
tryptophan
Tyrosine hydroxylase
Melatonin regulates circadian rhythms
Serotonin is a potent vasoconstrictor and
stimulator of smooth muscle contraction Inhibitio
n of MAO by iproniazid increases effects of
serotonin
9Eumelanin 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
10Biosynthesis of epinephrine and norepinephrine
11Biosynthesis of creatine and creatinine
Creatine is a high-energy storage compound in
muscle. ATP is made from creatine phosphate by
creatine kinase
12Metabolism of ?-aminobutyrate
13Porphyrins
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.
14Hemoproteins
15Uroporphyrins and coproporphyrins
16Biosynthesis of porphobilinogen
17Conversion 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.
18Decarboxylation of uroporphyrinogens
19Biosynthesis of porphyrin derivatives
20Addition of iron to protoporphyrin
21Absorption 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
22Intermediates, 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.
23Biochemical causes of the major signs and
symptoms of the porphyrias
24Summary of major findings in the porphyrias