Download Protein Metabolism

Protein Metabolism
Dr Hiba Alamodi
Kwashiokor
Metabolic disease that occurs in childhood 1-3 years age
results from a combined of protein deficiency and a high
caloric intake.
Features
muscle wasting with retardation of growth
Oedema due to hypoproteinemia
mental changes
Pigmentation of skin and hair changes
Increased of deposition of fat in subcutaneous tissues with
moon face
Anorexia, vomiting, and diarrhea
Protein Digestion
•Digestion of dietary proteins into
their constituent amino acids, begins
in the stomach and completed in the
intestine.
•Occurred by proteolytic enzymes
(proteases), synthesised as larger,
inactive forms known as zymogens.
After zymogens are secreted into the
digestive tract, they are cleaved to
produce the active proteases.
•Dietary proteins are denatured as a
result of acidic environment of the
stomach (pH is about 2) .
Digestion in the stomach
• pepsin is secreted by epithelial
cells of the stomach as inactive
form (pepsinogen) and activated
by the acid of the stomach lumen
and by itself (autocatalytic
process).
Pepsinogen
Pepsinogen
pH 1.5-2
pepsin
pepsin
pepsin
• Pepsin is an endoenzyme; it
doesn't attack the terminal
peptide bonds. It hydrolyses only
aromatic amino acids
Digestion by pancreatic enzymes
• Exocrine pancreatic enzymes
Trypsinogen
Trypsinogen
Entropeptidase
trypsin
Chemotrypsinogen
proelastase
trypsin
trypsin
procarboxypeptidase A, B
carboxypeptidase A, B
trypsin
trypsin
chemotrypsin
Elastase
trypsin
Digestion by intestinal enzymes
• Intestinal enzymes
Aminopeptidase
Tripeptidase
Dipeptidase
Action of proteolytic enzymes
Absorption of amino acids
• The amino acids and small peptides are transported into the
intestinal cells of the brush border by a family of amino acid
specific transports many of which require Na+
• At least four Na+ dependent amino acid carriers, located in the
apical brush border membrane of the epithelial cells
- neutral and aromatic a.as
- basic a.as (Arg, Lys, and ornithine) and Cys
- proline and hydroxyproline
- acidic a.as
Na+ dependent transport system
• Amino acid and Na+ ion are
transported together in the
same direction (symport).
• This transport is driven by the
Na+ gradient (high in the
intestinal lumen and low in the
intestinal cell).
• The cellular Na+ gradient is
achieved by active transporters
which utilized the energy of ATP
hydrolysis to transport Na+ out of
the cell and K+ into the cells.
• Then, facilitated transporters on
the serosal side transport the
amino acids into the blood
plasma.
Essential and Nonessential of a.as
Non essential amino
acids:
(1) are synthesised in the body if
an adequate amount is not
present in the diet.
(2) They are 11 amino acids, 10 of
them can be produced from
glucose, 11the one (tyrosine)
is synthesised from essential
amino acids (phenylalanine).
Note:- one of 10 amino acids
derived from glucose
(cysteine) obtains its sulfer
atom from essential amino
acids (methionine)
Essential amino acids
(1) Means their carbon skeleton can not
be synthesised in the body and are
required in the diet
(2) They are 9 amino acids
Note: arginine and histidine are
considered to be essential amino acid
during periods of growth
Protein turnover
• Means proteins are continually
synthesised and degraded
• Steady state, when the rate of
synthesis equals the rate of
deragation
• All proteins within cells have a halflife (t1/2 )
• Some proteins are inherently shortlived, within t1/2 of 5-20 minutes
whereas some proteins are present
for extended periods with t1/2 of
many hours or even days.
• A protein's half-life correlates with its N-terminal
residue
Proteins with N-terminal Met, Ser, Ala, Thr, Val, or
Gly have half lives greater than 20 hours.
Proteins with N-terminal Phe, Leu, Asp, Lys, or Arg
have half lives of 3 min or less.
• Process of protein degradation.
(A) Lysosomal proteasome
pathway
Is non-specific protein degradation.
Lysosomes are specialised organells that
operate at low pH (to denature proteins)
and contain proteases for proteins, lipases
for lipids and many other hydrolases.
Both internal proteins (enclosed in
vacuoles that fuse with lysosomes) and
external proteins (obtained via
endocytosis) are transported to lysosomes
where proteins are degraded and the
resulting amino acids either
Recycled for new protein synthesis or
Degraded for energy production or
storage
(B) Ubiquitin Related protein Degrdation
Ubiquitin
• Is a small regulatory
protein (76 a.as), found
in almost all tissues of
eukaryotic organisms.
• Highly conserved among
all eukaryotes.
• When covalently
attached to a protein,
ubiquitin marks that
protein for destruction
proteasome
Proteasome
• Is a 26S cylindrical protein
complex, consists of one 20S
core particle (CP) with multiple
internal proteolytic sites and
two 19S regulatory particles
(RP) that contain multiple
ATPase active sites
• CP of four stacked rings,
composed of two different
types of subunits (α and B)
Tagging of Proteins
• Ubiquitin tags and directs proteins to proteasomes for
degradation and recycling unneeded proteins
• The binding is achieved by the covalent attachment
(isopeptide) of the carboxyl-terminal glycine of ubiquitin with
€-amino group of lysine residues on target protein
• (ATP requiring process).
• Three enzymes involved,
Ubiquitin-activating enzyme (E1), Ubiquitin-conjugating
enzyme (E2), and ubiquitin ligase (E3)
Protein ubiquitination
Programmed protein degradation
(C) Apoptosis
Called programmed cell death, differ from nicrosis
Activated by a variety of signals, including
DNA damage
Entrance of a cell into the S phase under improper conditions
Lack of proper contacts of a cell extracellular matrix
Lack of necessary growth factors
Signals activate cytoplasmic protease, caspases
Apoptosis
characterized by
chromatin condensation
Nuclear fragmentation
cytoplasmic blebbing
cellular fragmentation into small
apoptotic bodies, phagocytosed by
adjacent cells and macrophages.
Apoptosis
Two main pathways activate the
caspase cascade and promote cell
death
Death receptor pathway (extrinsic
pathway) which relays apoptotic
messages via receptors on the cell
membrane
An intrinsic (mitochondrial)
pathway which relays apoptotic
message intracellularly