Notes on Nitrogen Metabolism (Proteins)

Nitrogen Metabolism

Proteins
Nucleic Acids

Topic Learning Outcomes

At the end of the topic, the students
should be able to:

• identify the main metabolic pathways

of proteins and the importance of the
pathways

• differentiate between the different

metabolic pathways

Nitrogen
Cycle

e.g. Rhizobium e.g. Pseudomonas,
e.g. Azotobacter Clostridium

e.g. Nitrobacter

e.g. Nitrosomanas

Sources of Biological Nitrogen

proteins nucleic
acids

nucleoprotein

• majority of useful

nitrogen for

metabolism

• not needed as

• dietary supplement
synthesis provided

by protein

degradation

Proteins Metabolism

digestion starts cellular concentration
in the stomach of a protein is a

by HCl and consequence of a
pepsin balance between its

then in small synthesis and
intestine by trypsin, degradation  protein
turnover and half-life
chymotrypsin,
carboxypeptidase, proteins degraded
by proteases or
aminopeptidase proteinases 

proteolysis forming
peptides and amino

acids



Amino Acids from Proteins
Degradation

transported into catabolized in 2
blood to gut to main stages:

liver  removal of
facilitated –NH2 group
diffusion using
transporters synthesis of
urea
degradation
of carbon
skeleton

Deamination

a process by takes place in
liver (also in
which an –NH2
group is removed kidney for Glu)
when amino
from a molecule acids are in

excess

involves 2 types: –NH2 group
transamination removed is
and oxidative converted into
ammonia while
deamination carbon skeleton

is further
degraded

Deamination: Transamination

transaminase or PLP
aminotransferase

++

amino acid 1 keto acid 1 keto acid 2 amino acid 2

e.g.

alanine transaminase

except Lys,
Thr, Pro,

hydroxyPro

Deamination: Oxidative Deamination

an oxidative occurs other amino
reaction that primarily acids are
occurs in all tissues on Glu
especially the liver deaminated via
combination of
transamination

and
deamination of

Glu:

utilized as glutamate
metabolic dehydrogenase
fuel, feeding
into citric
acid cycle

Other deamination mechanisms

• oxidation of L-/D-amino acids by L-/D-amino acid oxidase to

produce α-keto acid, ammonia and hydrogen peroxide:

L-amino acid oxidase

L-amino acid + FMN + H2O -keto acid + FMNH2 + NH3

D-amino acid oxidase

D-amino acid + FAD + H2O -keto acid + FADH2 + NH3

FMNH2 (FADH2) + O2 FMN (FAD) + H2O2

2H2O2 2H2O + O2

• action of dehydratase to deaminate amino acids containing –

OH group (e.g. Ser, Thr) and desulfhydrase to deaminate amino

acids containing –SH group (e.g. Cys):

serine dehydratase

Serine + PLP + H2O Pyruvate + NH3 + H2O

threonine dehydratase -ketobutyrate + NH3 +
Threonine + PLP + H2O H2O

desulfhydrase Pyruvate + NH3 + H2S

Cysteine + PLP + H2O

Urea Synthesis

excess nitrogen can uric acid by
be excreted in 3 major uricotelic

forms: organisms (e.g.
birds)
ammonium ions
by ammoniotelic urea by ureotelic
organisms (e.g. organisms (e.g.

fishes) terrestrial
mammals) 90%

synthesized in the

Asp CO2 liver, secreted into
the bloodstream,

taken up by the

kidney, excreted in

Ammonia the urine

(or Krebs-
Hanseleit Cycle

or Ornithine
Cycle)

Relationship between Urea Cycle and Citric

Acid Cycle

Kreb’s
Bicycle

Fumarate Arginine urea

Malate

Aspartate- Urea Cycle
Arginosuccinate

Shunt of Citric Argininosuccinate Ornithine
Acid Cycle

Oxaloacetate

-amino Aspartate carbamoyl
acid phosphate

Citrulljne

-keto
acid

Degradation of carbon skeleton

follows 2 glucogenic converted into
general amino acids one or more major
pathways
metabolic
ketogenic intermediates as
amino acids end products and
used as metabolic

fuel

amino acid that amino acid that
can be converted can be
into ketone bodies
converted into
through glucose through
ketogenesis gluconeogenesis

end products: acetyl-CoA or end products: pyruvate, α-
acetoacetate ketoglutarate, succinyl-CoA,
fumarate and oxaloacetate

Classification of glucogenic and ketogenic amino acids

Glucogenic amino Ketogenic amino Glucogenic and
ketogenic amino
acids acids
acids
Ala Leu Thr
Ser Lys
Cys Ile
Gly
Asn Phe
Asp
Met Trp
Val
Arg Tyr
Gln
Glu
Pro
His

Fate of carbon
in amino acids

Amino Acids Biosynthesis

Essential Non-essential 2 types of amino
acids based on
Ile Ala
capacity of
Leu Arg * mammals to
synthesized
Lys Asn
them
Met Asp
starting from the
Phe Cys formation of

Thr Glu carbon skeleton,
followed by the
Trp Gln assimilation of –

Val Gly NH2 group

His *

Pro

* amino acids that are Ser
essential to infants Tyr

Amino Acids Biosynthesis: Carbon Skeleton Synthesis

carbon skeleton is intermediates of
derived from citric acid cycle
commonly
available oxaloacetate -ketoglutarate
metabolic
intermediates intermediates of
pentose-
intermediates of phosphate
glycolysis pathway

pyruvate ribose-5-phosphate
3-phosphoglycerate

phosphoenolpyruvate

The Ser family

(Ser, Gly, Cys)

in animals,
Cys is

synthesized
from Met;
donor of –
SH group in
Cys (& Met)
comes from
homoCys

The aromatic family

(Trp, Tyr, Phe)

The pyruvate family

(Ala, Leu, Val)

The Asp family

(Asp, Asn, Thr, Lys,
Ile, Met)

The Glu family

(Glu, Gln, Pro, Arg)

His biosynthesis
(His)



Amino Acids Biosynthesis: Nitrogen Fixation

N2 is carried out by
converted microorganisms

into NH3 known as

nitrogenase diazatrophs (e.g.
complex
Rhizobium in legume
reductase – root nodules)
provides
nitrogenase –
electrons with uses electrons to
high reducing reduce N2 to NH3

power

Amino Acids Biosynthesis: Nitrogen Assimilation

NH3 is added includes 2
into nitrogen primary

containing reactions:

compounds

Ammonium assimilation into amino acids

The Ser family

The aromatic family

The pyruvate family (e.g. Ala)

The Glu family

The Asp family

Protein Synthesis

process in 1. amino acid
which cells synthesis
build proteins
2. transcription
Involves:
3. translation

5. protein 4. post-
folding translational
modification



Post-translational Modification and Protein Folding

Other roles of amino acids

Amino acids Precursors to synthesis of
Gln, Gly, Ser Purine nucleotides

Asp, Gln Pyrimidine nucleotides
Met Polyamines
Glutathione
Glu, Cys, Gly
Arg Creatine phosphate
Neurotransmitters
Tyr, Trp, Glu, Arg
Phe Lignin, aromatic compounds,
pigments
Tyr, His Hormones
Gly, Glu Porphyrins

Prepared by

DR. HAZLINA AHAMAD ZAKERI
School of Fundamental Science
Universiti Malaysia Terengganu (UMT)

21030 Kuala Terengganu
Terengganu
Malaysia

for

Semester I 2016/2017