Download Chapter 23 - Evangel University

Mary K. Campbell
Shawn O. Farrell
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Chapter 23
The Metabolism of Nitrogen
Paul D. Adams • University of Arkansas
Nitrogen Fixation
• Nitrogen fixation is the reduction of ____________:
• Bacteria are responsible for the reduction and
typically form symbiotic relationships that result in
nodules on the roots of leguminous plants
• Reduction is catalyzed by the nitrogenase enzyme
complex
• N2 to NH4+is a six-electron reduction
The Path of Electrons from Ferrodoxin to N2
Summary
• Nitrogen enters the biosphere by the process of
nitrogen fixation.
• Atmospheric nitrogen is converted to ammonia in
its conjugate acid form, ammonium ion.
• The nitrogenase enzyme found in root nodules of
leguminous plants catalyzes crucial reactions in
nitrogen fixation
Feedback Inhibition in Nitrogen Metabolism
• If there is a high level of
end product amino acid
or nucleotide, the cell
saves energy by not
making the compound
through a feedback
mechanism
• In summary, because
the biosynthetic
pathways for many
nitrogen-containing
compounds are long
and complex, feedback
inhibition helps ______
____________
Amino Acid Biosynthesis
• Common features of amino acid biosynthesis include:
_________________ & _____________________ transfers
• Glutamate is formed by reductive amination of
-ketoglutarate and NH4+
• Amidation of glutamate gives glutamine
• All amino acids are grouped into families based on their
__________________________________
Amino Acid Biosynthesis
Amino Acids and The Citric Acid Cycle
Role of Pyridoxal Phosphate in Amino Acid Rxns
• The biologically active form of vitamin ______ is
pyridoxal phosphate (PyrP)
• PyrP participates in the catalysis of a wide variety of
reactions of amino acids, including transaminations
and decarboxylations
• Pyridoxal phosphate forms an imine (a Schiff base)
with the -amino group of an amino acid
• Rearrangement gives an isomeric imine
• Hydrolysis of the isomeric imine gives an -ketoacid
and pyridoxamine
• All reactions are ______________________
Role of Pyridoxal Phosphate in Amino Acid Rxns
Role of Pyridoxal Phosphate in Amino Acid Rxns
• Transamination reactions switch ____________
___________ from one amino acid to an -keto acid
A Transamination Rxn Produces Serine
Serine to Glycine
• Serine to glycine is an example of a one-carbon
transfer
• The one-carbon acceptor is tetrahydrofolate, which
is derived from folic acid
Serine to Glycine
• Reduction of folic acid gives tetrahydrofolic
acid (THF), the ________________ form of
the coenzyme
• Tetrahydrofolate is a carrier of the one-carbon
groups shown in Figure 23.11 (see next slide)
Structure and Reactions of Folic Acid
Serine to Cysteine
• In ____________ & ____________, serine is
acetylated to form O-acetylserine
• The source of sulfur in plants and bacteria differ
from that in animals
• Sulfur donor comes from PAPS
(3’-Phospho-5’adenylylsulfate)
Serine to Cysteine
Methionine
• Methionine cannot be
produced in animals,
making it an _________
amino acid
• Methionine reacts
with ATP to form
S-adenosylmethionine
(SAM)
Cysteine in Animals
• SAM is a _________________________________
• The methyl group can be transferred to a number of
acceptors producing S-adenosylhomocysteine
Summary
• Two of the most important classes of reactions in the
biosynthesis of amino acids are transamination
reactions and one-carbon transfers
• The amino acids glutamate and glutamine are the
principal donors of amino groups in transamination
reactions
• Carriers of one-carbon groups include biotin, SAM,
and derivatives of folic acid
Essential Amino Acids
• The biosynthesis of proteins requires the presence of
all the constituent amino acids
• Some species, including humans, cannot produce all
of the amino acids and they must come from
____________ and are called essential amino acids
Amino Acid Catabolism
• First step is removal of the -amino group by
transamination
• -amino group is transferred to -ketoglutarate to
give glutamate and an -ketoacid
• The breakdown of carbon skeletons follows two
pathways, depending on the type of end product
• _________________ amino acid: one whose carbon
skeleton is degraded to pyruvate or oxaloacetate, both
of which may then be converted to glucose
• _________________ amino acid: one whose carbon
skeleton is degraded to acetyl-CoA or acetoacetylCoA, both of which may then be converted to ketone
bodies
Amino Acid Catabolism
Amino Acid Catabolism
The -amino group which
has been transferred to
-ketoglutarate has one of
two fates:
1. It may be used for
biosynthesis
2. It may be excreted as
a part of a nitrogencontaining product
The Urea Cycle
• The urea cycle is the central pathway in nitrogen
metabolism
• The nitrogen atoms come from several sources
• Steps of the cycle are outlined in Figure 23.18
(next slide)
Fig 23.18, p.688
The Urea Cycle
Fig 23.19, p.690
The Urea Cycle
Summary
• The carbon skeleton has two fates in the breakdown
process.
• Some carbon skeletons give rise to pyruvate or
oxaloacetate, which can be used in ______________
• Others give rise to acetyl-CoA or acetoacetyl-CoA,
which can form _______________
• The urea cycle, which has links to the citric acid
cycle, plays a central role in nitrogen metabolism.
• It is involved in both the anabolism and the catabolism
of _____________ _______________
Purine Biosynthesis
• Where do the atoms of purines come from?
How is IMP converted to AMP and GMP
• IMP is the precursor to AMP and GMP, and the
conversion takes place in 2 stages
Regulation of ATP and GTP
Purine nucleotide biosynthesis is
regulated by __________________
In Summary:
• The growing ring system of
purines is attached to ribose
phosphate during the synthesis
process
• The biosynthesis of nucleotides
requires considerable
expenditures of energy by
organisms in long and complex
pathways.
• Feedback inhibition at all stages
plays a key role in regulating the
pathway
Purine Catabolism
• The catabolism of purine nucleotides proceeds by hydrolysis
to the nucleoside and subsequently to the free base, which is
further degraded
• Salvage reactions are important in the metabolism of purine
nucleotides because of the amount of energy required for the
synthesis of the purine bases
• In Summary:
• Purines are degraded to uric acid in primates and are
further degraded in other organisms. Overproduction
of uric acid causes gout in humans
• Salvage reactions allow some purines to be reused
Purine Catabolism
Purine Salvage
Pyrimidine Biosynthesis and Catabolism
• The overall scheme of pyrimidine biosynthesis
differs from that of purines because the pyrimidine
ring is assembled ___________ it is attached to
ribose-5-phosphate
• Carbon and nitrogen atoms of the pyrimidine ring
come from carbamoyl phosphate and aspartate
• The production of N-carbamoylaspartate is the
_________________ step in pyrimidine biosynthesis
Pyrimidine Biosynthesis and Catabolism
Pyrimidine Biosynthesis and Catabolism
Pyrimidine Biosynthesis and Catabolism
• Feedback inhibition in
pyrimidine nucleotide
biosynthesis takes
place in several ways
Pyrimidine Biosynthesis and Catabolism
• Pyrimidine catabolism involves the breakdown of the
molecule first to the nucleoside, and then to the base
• This is similar to what happens in purine catabolism
Summary
• The ring system of pyrimidines is assembled
before it is attached to ribose phosphate
• During breakdown, the nucleoside is formed
first, then the base.
• Ring-opening reactions of the base complete
the degradation.
Conversion of Ribonucleotides to Deoxyribonucleotides
• Ribonucleoside diphosphates are reduced to
2’-deoxyribonucleoside diphosphates in all
organisms
• _______________ is the reducing agent
Conversion of Ribonucleotides to Deoxyribonucleotides
Conversion of dUDP to dTTP
The addition of a methyl
group to uracil to produce
thymine requires
___________________
as the one-carbon
carrier.
This process is a target
for cancer chemotherapy
Thymidylate Synthase