DEGRADATION OF

PROTEIN AND AMINO

ACID
By Group 1
 Our Team

Putri Kamilah
(2202101010017) Alya Mardhatillah
(2202101010080)
Hana Khairunnisa Dewi Ann Liberty Opanto
(2202101010076) (2202101010078)
 Our Team

Wafiq Nasna Thamrin

(2202101010087) Muhammad Rahmat
Al-Anshori
Fathia Azari Ramadhani Mhd Kasfi Muselza (2202101010177)
(2202101010094) Siagian
(2202101010163)
 Defenition

Protein degradation is part of a cell’s protein homeostasis

regulatory network that ensures unnecessary proteins are
removed from the cellular environment when they are no
longer needed or are damaged or faulty in some way.

 Process
There are two main enzyme systems
that play a role in the degradation
of damaged or unnecessary
proteins:
Lysosomes use the enzyme
The proteasome-ubiquitin
acid hydrolases to carry
mechanism that is ATP-
out the non-selective
dependent in the cytosol,
and the degradative
breakdown of intracellular
proteins ("autophagy") and
enzymes in lysosomes that
extracellular proteins
are not ATP-dependent.
("heterophagy") such as
Proteasomes selectively plasma proteins that are
decompose damaged or taken up into the cell by
short-lived proteins. the process of endocytosis
 Factors In
Protein
Degradation
 Factors

Protein degradation is the process by which

proteins are broken down into smaller peptides
and amino acids. There are several factors
that can contribute to protein degradation.
 Including
Proteases
Proteases are enzymes that
specifically cleave peptide bonds
between amino acids, resulting in
protein degradation. There are
different types of proteases that
can be found in cells, such as serine
proteases, cysteine proteases, and
metalloproteases.
Ubiquitin-
proteasome
This is a pathway for targeted protein
degradation in which proteins are
tagged with ubiquitin, a small protein,
and then degraded by the
proteasome. The ubiquitin-proteasome
system plays an important role in
regulating protein levels and
controlling cellular processes.
 Including
Autophagy Oxidative Stress

Oxidative stress, which is caused by

Autophagy is a process by which
an imbalance between the production
cells degrade and recycle their own
of reactive oxygen species and the
components, including proteins. In
ability of cells to detoxify them, can
this process, the proteins are
contribute to protein degradation by
engulfed by autophagosomes, which
causing damage to proteins and
fuse with lysosomes for
triggering their degradation.
degradation.
 Including
Denaturation
Denaturation is the process by which
proteins lose their three-dimensional
structure and become unfolded.
Denaturation can be caused by
changes in temperature, pH, or
exposure to chemicals, and can lead
to protein degradation.
Disease States
In certain disease states, such as
cancer or neurodegenerative
disorders, abnormal protein
accumulation can occur due to
impaired protein degradation
pathways. This can lead to protein
aggregation, which can be toxic to cells
and contribute to disease progression.
Signal & Site
of Protein
Degradation
Protein Degradation Signal

A degradation signal, or ‘degron’, is usually defined

as a minimal element within a protein that is
sufficient for recognition and degradation by a
proteolytic apparatus.
 Devides into
a). N-degrons and the ‘N-end rule
pathway’
In this degradation pathway, termed b). C-degron
the ‘n-end rule pathway,’ the half-life C-degron is any degron located at
of a protein is determined by the
the C-terminus of a protein.
nature of its n-terminal residue. The n-
terminal-region in a substrate that is
sufficient for ubiquitin-dependent
turnover constitute the ‘n-degron’.
Protein Degradation Sites

The principal sites for protein degradation in cells are

lysosomes and proteasomes. Both are involved in the
constitutive turnover of cellular proteins; typically,
short-lived proteins are degraded by proteasomes,
whereas lysosomes are responsible for the degradation
of long-lived proteins.
The Ubiquitin-Proteasome Pathway

-The major pathway of selective protein degradation in

eukaryotic cells uses ubiquitin as a marker that targets
cytosolic and nuclear proteins for rapid proteolysis.
-Ubiquitin is a 76-amino-acid polypeptide that is highly
conserved in all eukaryotes (yeasts, animals, and plants).
-The stability of many proteins is determined by whether
they become ubiquitinated.
Ubiquitination is a
multistep process: Activation
The initiating step, E1, is
known as the activating
step. An activating enzyme,
such as UBE1 (Ubiquitin-
activating enzyme E1),
activates ubiquitin and
begins a cascade of
enzymatic/substrate
activity.
Conjugation
The intermediate step, E2,
is known as the conjugating
step. A conjugating
enzyme, such as UBE2D2
(Ubiquitin-conjugating
enzyme E2 D2), grabs the
ubiquitin molecule and
creates an E2-Ubiquitin
conjugate intermediate.

Ligase
The final step, E3, is known as the ligase step. A
ligase, such as MurRF1 (muscle-specific RING-
finger protein 1), takes the ubiquitin molecule
from the Ub-E2 intermediate and completes the
pathway by conjugating the ubiquitin to the
target substrate.
 Lysosomal Proteolytic
Lysosomal proteolytic is a process of protein degradation which occurs
within lysosomes. Lysosomes are membrane-enclosed organelles that
contain an array of digestive enzymes, including several proteases,
which are responsible for breaking down proteins into smaller peptide
fragments or amino acids. The lysosomal proteolytic pathway plays a
crucial role in maintaining cellular homeostasis by eliminating damaged
or misfolded proteins, degrading internalized proteins from autophagy,
and recycling the resulting breakdown products for cellular processes
such as energy production or protein synthesis.

 The containment of proteases and other digestive

enzymes within lysosomes prevents uncontrolled
degradation of the contents of the cell. Therefore, in
order to be degraded by lysosomal proteolysis,
cellular proteins must first be taken up by lysosomes.
 Autophagy
Autophagy is a conserved cellular process whereby long-lived and
aggregated proteins, as well as excess and damaged organelles
are targeted by a double membrane vesicle or autophagosome for
elimination.
Basal autophagic activity is present in all cells and plays a
homeostatic role, allowing the use of basic molecular components
(amino acids) as building blocks or energy source.
Types:
Macroautophagy
Macroautophagy involves the sequestering of
cytosolic components within a double membrane
organelle called the autophagosome, transport
to the lysosome, and the subsequent cargo
degradation. Hereafter, macroautophagy is
referred to as autophagy.
Chaperone-Mediated Autophagy
Is unique from the other two types of
autophagy in that the process does not involve
generation of autophagic bodies. Similar to
microautophagy, CMA also occurs independent
of the autophagosome, however, CMA does not
involve lysosomal invagination

Microautophagy
Microautophagy is the process where
lysosomes directly engulf cytosolic
components via lysosomal membrane
invagination or protrusion without prior
formation of an autophagosome
 Conclusion
From the explanation we can conclude that protein degradation is the breakdown of
residual proteins into peptides or amino acids generally assisted by lysosomal enzymes
and proteasomes, short-lived proteins are degraded by proteasomes, while lysosomes
are responsible for the degradation of long-lived proteins. The ubiquitin-proteasome
system is a pathway for protein degradation that plays a vital role in regulating protein
levels and controlling cellular processes. The degron or degradation signal is divided into
the N-degron and the N-end, which determines the nature of the n-terminal residue. C-
degron is located at the C-terminus of the protein. Autophagy is where long-lived and
aggregated proteins are removed, allowing the use of amino acids as an energy source.
Types of Autophagy are differentiated according to the role of the lysosomes, namely
Macroautophagy, Chaperone-Mediated Autophagy, and Microautophagy.