Download Lecture 40

Lecture 40
Amino Acids 2
Amino Acid Biosynthesis
Nitrogen Fixation
Amino Acids as Precursors
Key Concepts
• Amino acid biosynthesis
• Herbicides and RoundUp Ready soybeans
• Nitrogen fixation in the biosphere
• Amino acids are precursors of numerous biomolecules
Amino acid biosynthesis
Atmospheric nitrogen is reduced to ammonia (N2 ---> NH3) primarily by
microorganisms that live in the soil and are associated with plant roots.
Humans need to obtain 9 of the 20 amino acids from their diet because
we lack the necessary enzymes for de novo biosynthesis.
There are at least 20 different pathways to specify the synthesis of all 20 amino
acids. Most, but not all, of these pathways are present in humans. Some
essential amino acids obtained in the diet provide substrates for other amino
acid biosynthetic pathways.
One example of this is the conversion of phenylalanine (essential amino acid) to
tyrosine (non-essential amino acid) by the enzyme phenylalanine hydroxylase.
Tyrosine is not only an
amino acid required for
protein synthesis, but also
a precursor for
neurotransmitter synthesis
(DOPA) and skin pigments
(melanins).
The enzyme tyrosinase is
required for melanin
synthesis.
Biosynthetic pathways found in plants are responsible for the production
of amino acids that are "essential" to humans. (Similar pathways are
found in bacteria).
Where does this come from?
Where do these come from?
Biosynthetic pathways found in plants are responsible for the production
of amino acids that are "essential" to humans. (Similar pathways are
found in bacteria).
Where do these come from?
Where do these come from?
Which human enzyme is required to keep tyrosine off of the Essential Amino
Acid list (i.e., how do humans make tyrosine?).
The most common form of albinism is due to a deficiency in the enzyme
tyrosinase. Would a diet rich in the amino acid tyrosine be an effective
treatment for albinism? Explain.
Why aren't individuals with the disease phenylketonuria (PKU) also albinos
considering that they have a deficiency in phenylalanine hydroxylase, the
enzyme required to convert phenylalanine to tyrosine?
Do individuals with PKU entirely lack proteins containing the amino acid
phenylalanine? Explain.
Herbicides and RoundUp Ready Soybeans
De novo synthesis of aromatic
amino acids (phenylalanine,
tryptophan, tyrosine) in plants and
bacteria requires the Shikimate
Pathway.
A key enzyme in this pathway
(EPSP synthase) is the target of
the herbicide glyphosate, also
known as Round-Up.
Genetically engineered crop plants such as soybeans have been
developed that are resistant to glyphosate to permit herbicide application
directly to fields.
The use of these "Round-Up Ready" crops is controversial for a
number of reasons. In fact, use of genetically modified organisms
(GMOs), including plants, is a hot topic both in the USA and
internationally.
If cows ate Round-Up Ready alfalfa that was recently sprayed with the
herbicide glyphosate, would they get sick? Explain.
Phenoxy-based herbicides such as 2,4-D are used on golf courses to
control broadleaf weeds that can grow within the turf grass. Do you think
that 2,4-D kills "weeds" but not grass by inhibiting the Shikimate pathway?
Explain.
Plants and most bacteria contain all the enzymes required for de novo
synthesis of amino acids, yet vertebrates synthesize only half of the 20
amino acids. What might explain this observation?
Nitrogen fixation in the biosphere
The nitrogen in amino acids, nucleotides and other biomolecules ultimately
comes from atmospheric nitrogen.
Conversion of N2 → NH3 is carried out by bacteria and blue-green algae.
Note that the pKa of NH3 is 9.2 so at physiological pH (~7), ammonia exists
as an ammonium ion NH4+
All organisms can use ammonia (NH3) in metabolic pathways to
synthesis amino acids, nucleotides and porphyrins, but only bacteria and
blue-green algae can fix atmospheric nitrogen into NH3.
The best studied nitrogen-fixing soil bacteria is Rhizobium which invades
the roots of leguminous plants such as soybean and saguaro cacti.
Why are the nodules red?
The Nitrogen Fixing Enzyme
Buchanon et al., Fig. 16.6
The biological process requires a complex enzymatic reaction involving
multiple redox centers. The two primary enzymatic activities are the
reductase and the nitrogenase.
Nitrogenases contain an iron-sulfur (Fe4S4) cluster for redox reactions
Nitrogen fixation is very costly with 16 ATP being hydrolyzed
for each N2 that is reduced.
N2 + 8 e- + 16 ATP + 16 H2O →
2 NH3 + H2 + 16 ADP + 16 Pi + 8 H+
Many desert plants are legumes, for example palo verde trees. What might
be the evolutionary advantage of this for palo verde trees?
Why do organic farmers rotate soybean crops through their planting fields?
Amino acids are precursors of numerous
biomolecules
A variety of
biomolecules are
derived from
amino acids
including
nucleotide bases,
sphingosine,
histamine, a
potent vasodilator,
the hormones
thryoxine and
epinephrine, the
pigment melanin,
the
neurotransmitter
serotonin, and the
nicotinamide ring
of NADH.
Two other important biomolecules
are nitric oxide, a first messenger
signaling molecule that is derived
from arginine, and the porphyrin ring
of hemes which is derived from
reactions utilizing glycine as the
source of nitrogen and for some of
the carbon atoms (other carbon
atoms come from acetate).
The first step in the biosynthesis of porphyrins in mammals is the
condensation of glycine and succinyl CoA to form δ-aminolevulinate.
Two molecules of δ-aminolevulinate condense to form porphobilinogen
which is the precursor to heme ring synthesis.
Genetic defects in porphyrin metabolism have been identified. The most notable
disease of this type is congenital erythropoietic porphyria which causes urine to
turn red, the skin to become light sensitive and teeth to glow in the dark (red
fluorescent teeth).
Moreover, red blood cells are short-lived due to very low levels of heme and
patients are anemic. One way people treated anemia in the middle ages was to
drink blood.
The known cause of erythropoietic porphyria is lack of the enzyme
uroporphyrinogen III cosynthase which leads to a buildup of the symmetric (but
physiological inert) intermediate uroporphyrinogen I. This compound absorbs UV
light.
Could it be that erythropoietic porphyria is the
biochemical explanation for the Vampire legend …
drinks blood, sensitive to light, fluorescent teeth.
It does make a good biochemistry story,
but perhaps a bit of a stretch.
Since erythropoietic porphyria is
a form of anemia, and drinking
animal blood was a common
treatment for anemic symptoms
(although it won't cure porphyria
because dietary heme cannot
enter red blood cells), it
wouldn't be a surprise if
someone with the disease was
in fact labeled a vampire by the
villagers (hard to miss the
fluorescent teeth).
In 1897 an Irish writer by the name of Bram Stoker
published a book called "Dracula" that has served as
the Vampire Guidebook. It is thought that Stoker's story,
which is based in Transylvania, is loosely tied to Vlad III
Dracula, aka Vlad Tepes, aka Vlad the Impaler, who
lived in Transylvania in the 15th century.
Our good buddy Vlad Tepes
Bram Stoker
Vlad Tepes’ father was known as Vlad Dracul, or
Vlad the Dragon
“Dracul” means dragon and devil in Romanian.
Dracula, with the “a” on the end, means son of
Dracul. So, Vlad Dracula was the son of the
dragon or the son of the devil.
He ruled much of what is now modern day
Romania with an iron fist. If any village or town
opposed him in his conquests, he would take half
of the adults and impale them on stakes set in a
large circle. He would then have a banquet in the
middle of the circle, forcing the rest of the villagers
to watch. His reputation spread quickly. Very
effective crowd control, don’t you think? No one
knows if he drank the blood of the impaled.
Dracula’s Childhood Home
Sighisoara, Transylvania, Romania
Copyright © 2003 David R. Gang
Copyright © 2003 David R. Gang
Stoker set Dracula’s “Castle” in the Tihutsa Pass,
in Eastern Transylvania, Romania
This is what the real pass looks like. Not the Craggy Rocky
Desolate Place that the movies lead you to believe, is it!
Copyright © 2003 David R. Gang
The only Dracula’s “Castle”
you find in the Tihutsa Pass
is this Hotel
Dracula’s “Castle” in Bran
Transylvania, Romania
Transylvania, Romania
Copyright © 2003 David R. Gang
Copyright © 2003 David R. Gang
The rooms all have Dracula themes
Blood red satin sheets, black curtains,
stuff like that.
This place claims to be Dracula’s
Castle, but Vlad probably only stayed
a few nights here. It belonged to
someone else. He never lived here.
Great touristy place.
If you want to see a truly great “Dracula” movie…
Check out Werner Herzog’s 1979 film:
Nosferatu, Phantom Der Nacht
Starring:
Klaus Kinski as Dracula,
Isabella Adjani as Lucy Harker,
and Bruno Ganz as Jonathan Harker.
This is a creepy, eerie, make your skin crawl
movie without the gore of most Vampire
movies.
Also has significant political statements
about the Communist Regimes of Eastern
Europe and Government in general.
Black Plague as a metaphor
And the rats …