Welcome to class of
Metabolism of nitrogen compound
Dr. Meera Kaur
Learning objectives
• To understand:
– The process by which atmospheric nitrogen is made
available to plants and animal.
– To understand the transamination reactions.
– The reaction of oxidative deamination.
– The reactions of urea cycle.
– The inborn errors of amino acid metabolism
Nitrogen fixation
Nitrogen enters the biosphere by nitrogen fixation
• Few plants can from nitrogen- containing compounds from
nitrogen in air, no animals can, but certain bacteria can. It is
through nitrogen-fixing bacteria that atmospheric nitrogen enters
the biosphere- the domain of living things. Nitrogen-fixing
bacteria reduces atmospheric nitrogen to ammonia, a water
soluble form of nitrogen that can be used by plants and animals.
• Plants and animals incorporate ammonia into nitrogen
compound such as proteins. The plants and animal die and
decay, aided by other bacteria. Decaying matter returns nitrogen
to the soil as ammonia, nitrite ions or nitrate ions, Moreover,
some nitrogen gas is returned to the atmosphere. This flow of
nitrogen between the atmosphere and, the earth with its living
creatures is the nitrogen cycle.
Root nodules from clover
The nitrogen cycle
Protein turnover
Proteins are continuously hydrolyzed and synthesized by the body
• In the human body dietary proteins are hydrolyzed to their
constituent amino acids as a part of digestion. Many of the body’s
proteins are continuously hydrolyzed and synthesized within the
cells. This dynamic process is called protein turnover.
• The enzymes responsible for intracellular hydrolysis of proteins
are cathepsins — a class of peptidases similar to trypsin, peosin
and chymotrypsin.
• In cells, the cathepsins are confined to the lysosomes, where the
protein degradation occurs.
• We have already discussed about translation— the process of
protein synthesis.
Amino acid metabolism
Amino acids meet several cellular needs
• Amino acids produced by digestion of dietary protein and during
protein turnover in the body cells become part of the body’s
amino acid pool.
• The amino acid pool is the total quantity of free amino acids
present in tissue cells, plasma and other body fluids.
• The amino acids of amino acid pool are available for several
cellular needs.
Transamination reactions
Amino acids part with their amino groups by transamination reactions
•
Many of the reactions of amino acid metabolism require that amino acids first
lose their alpha amino group. The most common way for this to occur is by
transamination — the transfer of an amino group from one molecule to
another. An intermediate of the citric acid cycle, -ketoglutaric acid, is the
usual acceptor of the amino group. The products of the reaction are an -keto
acid and glutamic acid.
•
Transamination reactions are catalyzed by transaminases. Transaminases
are the indicators of disease or trauma that affects tissues. The principal
transaminase of liver is glutamic- pyruvic transaminase (GPT), an enzyme
that catalyzes the formation of pyruvate from alanine.
•
The principal transaminase of the heart muscle is glutamic- oxaloacatic
transaminase (GOT), an enzyme that catalyzes the formation of oxaloacetate,
one of the intermediates of the citric acid cycle, from aspertic acid.
•
Transamination
Oxidative deamination
• Glutamic acid serves as the depot of receiving amino groups
removed from amino acids by transamination reactions. Since
there is limited quantity of -ketoglutarate in cells, it must be
regenerated so that the transamination reactions and citric acid
cycles continue
• The -ketoglutarate is regenerated from glutamic acid by an
oxidation reaction catalyzed by glutamate dehydrogenase. The
enzyme use NAD+ as co anzyme. The chemical reaction is called
oxidative deamination.
Glutamic acid + water
Ammonium ion + -ketoglutarate
The urea cycle…
Ammonia produced by oxidation of glutamic acid is
excreted as urea
• With the regeneration of -ketoglutarate the cellular
concentration of -ketoglutarate is restored. Oxidative
deamination has also produced ammonia. Ammonia even in low
concentration is very toxic to brain cells and can result in coma
and death. The reason for this toxicity is unclear. If ammonia is
permitted to accumulate it may also reverse the activity of
glutamate dehydrogenase and this will deplete the supply of ketoglutarate to citric acid cycle. Whatever the reasons for
ammonia’s toxicity, it is important that it be removed from the
body. This is accomplished by the reactions of the urea cycle.
Steps of the urea cycle
Step 1: Carbamoyl phosphate reacts with ornithine. The product of this
reaction is citruline.
Step 2: Citruline reacts with aspartic acid to give a complex molecule
called arginosuccinic acid.This reaction requires the expenditure of two
more high energy phosphate bond of ATP.
Step 3: An enzyme now cleaves the arginosuccinic acid into arginine and
fumaric acid. Fumaric acid is one of the intermediates of the citric acid
cycle.
Step 4: The production of urea occurs when arginine is hydrolyzed to
ornithine and urea. The ornithine re enters the urea cycle by reacting
with another molecule of carbamoyl phosphate. After entering the blood
stream, urea is filtered by the kidneys and disposed of in the urine.
The four reactions of the urea cycle
Nitrogen metabolism in context
Amino acid catabolism
Inborn errors of metabolism…
Inborn errors of metabolism…
Inborn errors of metabolism
Xanthine oxidase
Urease breaks down urea
Urease