4. Derived from beta-alanine and histidine
Anserine is formed by methylation of carnosine
by S-adenosylmethione
(beta-alanine is derived from cytosine)
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
Decarboxylation of histidine
forms histamine. Other compounds
arising from histidine are shown here
5.
6. 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.
7. 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.
10. Melanin polymers contain both
eumelanin and pheomelanin in
varying amounts.
Albinism accompanies defective
melanin biosynthesis. Tyrosine
hydroxylase-negative albinos lack
all visual pigment
11.
12. Creatine is a high-energy storage compound in muscle. ATP is
made from creatine phosphate by creatine kinase
13.
14. 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.
15.
16.
17.
18. 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.
19.
20.
21.
22. 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
23. 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.
Editor's Notes
Many metabolites and pharmaceuticals are excreted as water-soluble glycine conjugates. The capacity of the liver to convert benzoate to hippuric acid formerly was used to assess liver function.
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.
Addition of inhibitors of ornithine decarboxylase, the enzyme that catalyzes the initial reaction in polyamine biosynthesis, triggers overproduction of ornithine decarboxylase. (hence, the machinary that makes the protein is regulated tightly in order that a supply of the precursors to spermidine and spermine is always available.
ALA synthase is the rate-controlling enzyme in porphyrin biosynthesis. ALA dehdratase is sensitive to inhibition to lead, as can occur in lead poisoning.
