protein metabolism

Nitrogen Metabolism:

Proteins

Topic At the end of the topic, the students
Learning should be able to:
Outcomes
•identify the main metabolic pathways

of proteins and the importance of the
pathways

•differentiate between the different

metabolic pathways

Nitrogen
Cycle

Proteins Nucleic
Acids

Sources of • majority of useful
Biological nitrogen for
Nitrogen metabolism

• not needed as dietary
supplement
• synthesis provided by

protein degradation

Proteins •cellular concentration of a protein is a consequence of a
Metabolism
balance between its synthesis and degradation  protein
turnover and half-life

•proteins degraded by proteases or proteinases  proteolysis

forming peptides and amino acids

 protein digestion:
in stomach by hydrochloric

acid and pepsin
 in small intestine 
trypsin, chymotrypsin,

carboxypeptidase,
aminopeptidase



• amino acids are used in three ways in the body:
 protein synthesis

 synthesis of a variety of other compounds  e.g. purines and

pyrimidines; catecholamines; neurotransmitters; histamine

and porphyrins

Amino Acids in •  as a biological fuel
Proteins however, amino acids are not stored in the body or excreted:

Metabolism  amino acids pool:
grand mixture of amino acids
available in the cell derived from
dietary sources or the
degradation of protein
nitrogen balance  negative
and positive

Amino Acids •amino acids to be degraded are transported
Catabolism
into blood to gut to liver  facilitated
diffusion using transporters

•3 major steps in catabolism of amino acids:

removal of amino group by deamination
urea synthesis

degradation of carbon skeleton

Amino Acids •a process by which an amine group is
Catabolism:
removed from a molecule
Deamination
•takes place in liver (also in kidney for Glu)

when amino acids are in excess

•amino group removed is converted into

ammonia while carbon skeleton is further
degraded

•involves 2 types: transamination and

oxidative deamination

•transfer of an amine group from one molecule to another
•results in the exchange of an amine group on one acid with a

ketone group on another acid:

Transamination

e.g.

• an oxidative reaction that occurs under aerobic conditions in all tissues but

especially the liver

• occurs primarily on Glu

α-ketoglutarate is then utilized as metabolic fuel, feeding into citric acid
cycle

ammonia produced is converted to urea

Oxidative • other amino acids are deaminated via
deamination
combination of transamination and
deamination of Glu:

glutamate dehydrogenase

• excess N excreted as ammonium ion (in fish), urea (in terrestrial
animals) and uric acid (in birds)
• formation of urea from ammonia, CO2 and Asp in a cyclic pathway
referred to urea cycle  disposes 90% of surplus N
• urea is synthesized in the liver, secreted into the bloodstream,

taken up by the kidney, excreted in the urine

Amino Acids Urea CO2
Catabolism: Asp

Urea Synthesis

Ammonia



Relationship Between Urea Cycle and Citric Acid Cycle

(i.e. Kreb’s Bicycle)

Amino Acids • carbon skeleton is converted into one or more major
Catabolism:
metabolic intermediates as end products and used as
Degradation of metabolic fuel:
Carbon
Skeleton  pyruvate
 α-ketoglutarate

 succinyl-CoA
 fumarate

 oxaloacetate
 acetyl-CoA
 acetoacetyl-CoA

• follows 2 general pathways:

 glucogenic amino acids
 ketogenic amino acids

• glucogenic amino acids:
 amino acid that can be converted into glucose
through gluconeogenesis
 end product pyruvate, α-ketoglutarate,
succinyl-CoA, fumarate and oxaloacetate

• ketogenic amino acids:
 amino acid that can be converted into ketone
bodies through ketogenesis
 end product either acetyl-CoA or acetoacetate

both carbon atoms in the ketone body are
ultimately degraded to CO2 in the citric acid

cycle

Classification of glucogenic and ketogenic amino acids

Glucogenic amino Ketogenic amino Glucogenic and
acids acids ketogenic amino

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

Fate of carbon in
amino acids

•living organisms differ in their capacity to

synthesize amino acids:

Amino Acids e.g. mammals can only synthesize some of the
Biosynthesis standard amino acids:

essential amino acids are amino acids that
must be obtained from diet

non-essential amino acids are amino acids
that can be synthesized

Classification of essential and non-essential amino acids

Essential Non-essential
Ile Ala
Leu Arg*
Lys Asn
Met Asp
Phe Cys
Thr Glu
Trp Gln
Val Gly
His*
* amino acids that are essential Pro
to infants Ser
Tyr

•carbon skeleton is derived from

commonly available metabolic
intermediates:

 -ketoglutarate
 oxaloacetate
 3-phosphoglycerate

 pyruvate
 phosphoenolpyruvate
 ribose-5-phosphate

The Glu
family

(Glu, Gln, Pro
Arg)

The Asp
family

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

The Ser
family

(Ser, Gly, Cys)

in animals,
Cys is

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

The pyruvate
family

(Ala, Leu, Val)

The aromatic
family

(Trp, Tyr, Phe)

His biosynthesis

•ultimate source of nitrogen for amino acid
biosynthesis  atmospheric N2

•cNNyH2am3n,oubbsytancbiteterrroiegadeaunncfdeidxtahttoeioasnymmbeybtsiaoobtmoicleibcsaaolclityleburaisacetfeurlifao, rm,
Rhizobium that invade the root nodules of
leguminous plants

•namitrmogoennia-c, oNnHt3aiinsiansgsicmomilaptoeudnbdysa(lalmorignaonaiscmidss,into
nucleotides, etc.)



Nitrogen fixation •conversion of N2 to NH3
•only a few microorganisms

involved = diazatrophs

•invasion of legume roots by

Rhizobium form root nodules
where fixation takes place

•fixation is carried out by the

nitrogenase complex:
reductase – provides

electrons with high reducing
power; and

nitrogenase – uses electrons
to reduce N2 to NH3

• assimilation of NH3 into organic nitrogen-containing compounds
• 2 main reactions:

Nitrogen
assimilation

• the amino nitrogen in Glu and the amide nitrogen in Gln are then
used further to give rise to other compounds

Ammonium assimilation into amino acids

The Glu family

The Asp family
The Ser family

The pyruvate family (e.g. Ala)
The aromatic family

Protein •process in which cells build proteins
Synthesis •refers to a multi-step process, beginning with

amino acid synthesis and transcription of
nuclear DNA into messenger RNA, which is
then used as input to translation

•after synthesis, proteins may undergo post-

translational modification and protein folding

Protein folding process

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

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

I end the lectures with these
reminders…