Protein Metabolism
Dr Hiba Alamodi
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 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).
process).
Pepsinogen pepsin Pepsinogen pepsin
• Pepsin is an endoenzyme; it doesn't attack the terminal
peptide bonds. It hydrolyses only aromatic amino acids
pH 1.5-2 pepsin
Digestion by pancreatic enzymes
• Exocrine pancreatic enzymes
Trypsinogen trypsin Trypsinogen trypsin
Entropeptidase trypsin
Chemotrypsinogen chemotrypsin proelastase Elastase
procarboxypeptidase A, B carboxypeptidase A, B
trypsin
trypsin
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
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 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 (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 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 half- life (t1/2 )
• Some proteins are inherently short- lived, 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.
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 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
€-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 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 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 Death receptor pathway (extrinsic
pathway) which relays apoptotic messages via receptors on the cell membrane
An intrinsic (mitochondrial)
pathway which relays apoptotic message intracellularly
