PROTEIN METABOLISM

A. Yasmin Syauki
Nutrition Department
Faculty of Medicine-Hasanuddin University
syaukiyasmin@gmail.com
Learning objectives :
 To describe how amino acids form proteins
 To distinguish between essential and non-essential
amino acids and explain why adequate amounts of
each of the essential amino acids are required for
protein synthesis
 To define the general principles of protein turnover
Learning objectives :
 To learn how protein metabolism is controlled by
hormones and mediators
 To accurately determine how and why amino acids
pathways adapt to protein supply
 To understand why protein starvation ultimately leads
to morbidity and mortality
 Introduction
 Thousands of substances in the body are made of
proteins.
 Protein form the major part (after water) of lean body
tissue, totalling about 17% of body weight.
 Amino acids –the building blocks for protein- are
unique because it contain nitrogen bonds to carbon.
 .
 Definition
 Protein : High-molecular-weight polypeptides.
 Amino acids : protein’s unit structures or building
blocks of protein.
 Peptide : Amide linkage of amino acids (linear
linkage of amino acids).
 Proteins
• Proteins are composed primarily of carbon, hydrogen,
nitrogen,and oxygen. However, some contain sulfur.
• They are all composed of structural monomers called
amino acids.
• Their differences from organism to organism is due to
differences in the DNA which contains the
instructions for their formation. Ex. Eye color, Blood
type
 Protein Functions
• Structure: Building structural components of organisms
(collagen, elastin, keratin, microtubules, microfilaments)
• Regulation of metabolic processes: Hormones (insulin)
• Carrying out of metabolic processes:
Enzymes
• Membrane component: Carrier proteins, Protein pumps,
Transport of materials through membrane phospholipid layers
• Self and non-self recognition: Major histocompatibility
complexes (Tissue rejection, immune responses).
• Membrane receptors: Hormone receptors and
neurotransmitter receptors.
 Amino Acids: Structural Monomers
Amino acids derive their name due
to the presence of an amine
group and a carboxylic group
as part of their composition.
They have a central carbon
with the amine group, a
carboxyl group, a hydrogen,
and a variable group (R group)
attached to it. The variable
group is what is different from
amino acid to amino acid and it
is what give the amino acid its
identity. There are twenty
different variable groups,
therefore there are twenty
different amino acids.
Eleven of them are essential
and others are non essential
Amino Acid Variety
 Peptide Bond, Dipeptide, and
Polypeptide Formation
A peptide bond is the bond that
is created when two amino
acids are covalently bonded
together. The carboxyl
group of the first is bonded
to the amine group of the
second. This is carried out
by a dehydration synthesis
reaction with the loss of a
water molecule. This forms
a dipeptide.
 Peptide Bond, Dipeptide, and
Polypeptide Formation
H H O H H O

N C C –OH + N C C –OH

H R1 H R2

H2O

The peptide bond This is called a

H H O H O
is created between dipeptide. If the
the carboxyl carbon process is
N C C– N C C –OH
of the first amino acid repeated many
and the amine group H times a
R1 H R2
of the second amino polypeptide is
acid. Peptide Bond formed.
 Levels of Protein Structure
Proteins are very complex molecules and their
shape or structure determines their function.
Most proteins have 4 levels of structure. They
are:
a. Primary Level
b. Secondary Level
c. Tertiary Level
d. Quaternary Level
If any level of structure is changed it can create
faulty or nonfunctioning proteins!
 Levels of Protein Structure
The Primary Level is
determined by the
number of amino
acids, the type of
amino acids, and
the sequence of the
amino acids in the
polypeptide chain.
 Levels of Protein Structure
The Secondary Level is
due to interactions
between amino acids in
the chain, usually due
to hydrogen bonding
between oxygen and
hydrogen atoms in
different amino acids.
Two general forms are
taken. Alpha helix, a
spiral structure,
common in globular
proteins, or a Beta
pleated sheet structure,
common in structural
proteins.
 Levels of Protein Structure
The Tertiary Level is due to
the “folding over” of the
alpha helical or beta
pleated sheet structure
on itself. This
configuration is due again
to hydrogen bonding,
hydrophobic
interactions, ionic
bonding interactions,
and the interaction of
sulfur groups on the
variable groups of some
amino acids forming
weak interactions called
disulfide bridges.
 Levels of Protein Structure
The Quaternary Level
of structure is due to
the interactions of
more than one
polypeptide chain to
form the complete,
functional protein.
Hemoglobin and
antibodies exhibit this
level of structure.
Levels of Protein Structure
 Example of Modification in Levels
of Protein Structure
Sickle-cell anemia is
due to a change in
protein structure at
the primary level.
Once the change is
made at the primary
level it has an effect
on all subsequent
levels. Resulting the
formation or irregular
hemoglobin protein
that cause the
molecule to take on
an irregular form
which in turns affects
its normal function
and the shape of the
erythrocytes (red
blood cells).
 Reactions in Amino Acid
Metabolism
 Two types of reaction, both perform the same
function -> removal of the amino group (-NH2)
 Transamination : conversion of any amino acid
into alanine, glutamate or aspartate
 Oxidative deamination :
 Nucleic Acids
• Composed of carbon, hydrogen, oxygen,
nitrogen, and phosphorus
• Carriers of the genetic code (recipe book
for proteins)
• Two types: DNA (deoxyribonucleic acid)
and RNA (ribonucleic acid)
• Molecule responsible for heredity
 Nucleotide Monomers
Nucleic acids are composed of many monomers
linked together by dehydration synthesis. These
monomers are called nucleotides
(nucleosides). These monomers are
composed of a monosaccharide
(deoxyribose in DNA or ribose RNA), a
phosphate group, and a nitrogenous base.
The nitrogenous bases found in DNA are
adenine A, Thymine T, Guanine G, and
Cytosine C. The nitrogenous bases found in
RNA are Adenine A, Guanine G, Cytosine C,
and Uracil U, which replaces thymine.
Nucleotide Structure
 DNA Structure
The structure of DNA was
discovered by an American
scientist (James Watson) and
a British scientist (Francis
Crick) based on the work of
Rosalind Franklin and Maurice
Wilkins. In 1962 Watson and
Crick received the Nobel Prize
for their work. Wilkin later
received a Nobel Prize for
work relating to his
contribution. Rosalind Franklin
however, never received a
Nobel Prize because she died
of cancer before she was
publicly recognized for her
contributions to this effort.
The Double Alpha Helix of DNA
DNA is a double stranded, 5’
alpha helical molecule.
Each strand is composed
of nucleotide covalently
bonded between their
phosphate groups and
the deoxyribose sugar
components in a 5,3
linkage between the
sugars and phosphates.
The nitrogenous bases
point outward from the
linear alternating sugar
phosphate backbone.
3’
The Double Alpha Helix of DNA
When two strands of DNA
join to form the alpha
helix, it is due to
hydrogen bonding
between the
complimentary purine and
pyrimidine bases on each
complimentary strand.
Adenine forms hydrogen
bonds with Thymine and
Guanine forms hydrogen
bonds with Cytosine.
This is called
Complimentary Base
Pairing.
The Double Alpha Helix of DNA
The complimentary
strands run in
opposite directions or
anti-parallel to each
other.
The Double Alpha Helix of DNA
The strands begin to spiral and due to hydrogen
bonding takes on the double alpha helix form.
 Comparing and Contrasting DNA
and RNA
• DNA bases (A,T,G,C) • RNA bases (A,U,G,C)
• Deoxyribose sugar • Ribose sugar
• Original information for • Working copy for making
making proteins proteins
• One form or type • Variety of forms, m-RNA,
• Found primarily in the t-RNA, r-RNA
nucleus forms • Found in nucleus and
chromosomes during cell through the cell
division • Smaller molecules (single
• Large molecule (double stranded)
stranded)
 Protein turnover
 Protein represent the largest pool of amino acids (AAs) in
the body (99,8 %).
 Free Aas represent only small fraction, 85% are in
intracellular and 15-20% in the plasma and the
interstitium.
 Free AAs and protein pools are balanced, on a 24-hour
basis, with the whole body protein synthesis of 300 g of
proteins and an equivalent degradation.
 Food provides ≈ 80 g of proteins which with a similiar
loss in urine (88%) or by other routes (12%).
 Protein turnover
 Protein balance (B), which is the difference between
synthesis (S) and catabolism (C).
 B=S-C
 In the healthy adults, the balance is 0.34 g N/kg (S=C)
 However, protein balance is a dynamic equilibrium with
an anabolic phase in the post-prandial state and a
catabolic phase between meals.
 Whether these variations result from variations in
synthesis rate, catabolism rate or a combination of both
remains to be elucidated.
 Protein turnover
 The whole-body net balance is equal to the sum of the net
balances of individual tissues.
 The rate of protein synthesis (and catabolism) varies strongly
from one tissue to another.
 The mass of given tissue has to be taken into consideration
when calculating its contribution to whole-body net balance.
 Protein turnover is lower in muscle than in other tissues but
the mass is much higher, resulting in the high contribution of
muscle to protein turnover.
 The certain situations also can influence the whole-body net
balance.
 Protein turnover
Table 1. Protein synthesis according to tissue

The tissue Protein synthesis

Intestinal mucosa 123 ± 4
Bone 90 ± 2
Liver 86 ± 6
Skin 64 ± 2
Heart 20 ± 1
Muscle 17 ± 5
 Protein turnover
Table 2 Physiopathological modifications of protein turnover

Conditions/situations Synthesis Catabolism Net balance

Children ↑↑ = ++
Elderly ↓ = -
Sport training ↑↑ ↑ +
Starvation ↓↓ ↓ -
Cancer ↓ ↑ -
Surgery ↓ = -
Burn, sepsis ↑ ↑↑↑ --
 Regulation of protein and amino acid
metabolism by hormones and mediators
Hormones :
Insulin
 Insulin exerts actions of every level of AA metabolism :
 It increases the cell transport of numerous AAs, especially in the
muscle and liver;
 It favors net protein anabolism by decreasing protein breakdown
 It inhibits gluconeogenesis by both decreasing the availability of
precursors and inhibiting key enzymes in this pathway.
 Regulation of protein and amino acid
metabolism by hormones and mediators
Hormones :
Growth hormone
 Growth hormone stimulates protein synthesis, increases
cellular AA uptake and stimulates IGF-1/Sm-C release. IGF-
1/Sm-C release in turn promotes protein synthesis.
Testosterone
 Testosterone stimulates protein synthesis in muscle
Cortisol and glucagon
 Cortisol and glucagon coordinate to modulate protein
turnover, leading to unidirectional flux of nitrogen from the
muscle to lthe liver. .
 Regulation of protein and amino acid
metabolism by hormones and mediators
Hormones :
Cortisol and glucagon
 In muscle, cortisol increases protein breakdown and favors free
AA release in the bloodstream.
 In the liver, glucagon stimulates AA uptake and flavors their
use in gluconeogenesis.
Cathecolamines
 Considered as catabolic hormones for lipids and carbohydrates.
 But, for proteins, cathecolamine are actually anabolic,
promoting proteosynthesis and inhibiting protein breakdown in
muscle and possibly the liver.
 Regulation of protein and amino acid
metabolism by hormones and mediators
Pro-inflammatory cytokines :
Physiologically, pro-inflammatory cytokines play an only minor
role (except perhaps in the elderly)
In the disease, however, pro-inflammatory cytokines like tumor
necrosis factor α and interleukin 1 and 6 are overproduced and
act synergistically with glucagon and cortisol on AA
metabolism.
 Metabolism according to prandial phase
In the fed state, after digestion and transport into enterocytes,
AAs are used for neosynthesis (e.g nucleotida synthesis) and
energy supply (mainly glutamine)
To make neosynthesis (protein synthesis), should maintance AA
in the body.
There are 20 AA, 9 of which are essential.
Key reactions of AA are transamination and oxidative
deamination
 Metabolism according to prandial phase
For energy supply (gluconeogenesis) :
1. The transfer of AAs from muscle to liver
2. The removal of the amine moeity from the AAs.