PROTEIN METABOLISM
PROTEINS
Function of Proteins
Catalytic functions
Protection
Transport
Structure
Regulation
Nerve İmpulse transmission
Movement
Receptor
Storage
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• Humans require 20 aminoacids - 9 are essential
- 11 are not essential
• Cellular proteins are synthesized by ribosomes using the information encoded in mRNA
• Proteins are composed of aminoacids that are linked together
by peptide bonds
Hydrolysis
Aminoacid molecules
N H +H
H
C C
O
O- H
R
Aminoacid structure
Protein metabolism is a chemical procedure
Break down dietary or endogenous proteins into amino acids
Ingested dietary proteins are metabolised to amino acids via peptide bond cleaving enzymes (proteinases)
Absorbed into the bloodstream
PROTEIN METABOLISM
No aminoacid stroge in the body
Aminoacids can be provided by diet, de novo synthesis of aminoacids and protein degredation
Aminoacid Pool
Endogenous body proteins Exogenous diyet proteins Non essential aminoacid synthesis
Aminoacid Pool
Protein Synthesis
Synthesis of molecules containing nitrogen
Conversion of amino acids to glucose, glycogen, fatty acids Aminoacid oxidation
Negative Nitrogen Balance
Nitrogen excretion > nitrogen content of the diet
Tissue destruction.
Positive Nitrogen Balance
Nitrogen excretion < nitrogen content of the diet
Protein formaiton
DIGESTION OF DIETARY PROTEINS
A large amount of dietary nitrogen is originated from protein
Proteins are hydrolyzed……Di, tripeptides, aminoacids are produced……….
and they can be absorbed.
Proteolytic enzymes
Responsible for degrading proteins
They are produced by stomach, pancreas, small intestine
Digestion of Proteins (Stomach)
Pepsin is the digestive enzyme in the stomach
Pepsin, pH 2-3 active, pH> 5 inactive
HCl; killing bacteria, protein denaturation, partial activation of pepsinogen
Pepsinojen, is the inactive form of pepsin, activated by HCl and a partially active pepsin enzyme.
DIGESTION BY PANCREATIC ENZYMES
The pancreas secretes pancreatic digestive enzymes. Trypsin, chymotrypsin, carboxypeptidase, elastase.
These proteolytic enzymes are responsible for breaking down polypeptides into smaller peptides.
Secretin and cholecystokinin are hormones secreted by the small intestine.
The secretin stimulates the release of bicarbonate by the pancreas
Cholecystokinin causes digestive enzymes to reach the small intestine by the pancreas.
It contains pancreatic fluid, water, bicarbonate and digestive enzymes.
Zymogens;
Include extra amino acids
Catalytically inactive form of an anzyme
Removal of extra amino acid sequence → appropriate folding → catalytically active enzyme
Activation of
Zymogens
PANCREATITIS
Pancreatic Zymogens
Reach to the small intestine
Then they are normally activated
Inappropriate activation of trypsin Pancreatitis
Normally
Dangeorus sitution occurs
Trypsinogen Trypsin Enterokinase
Trypsin
Chymotrypsin Elastase
Carboxipeptidase A Carboxipeptidase B Chymotrypsinogen
Proelastase
Procarboxipeptidase A Procarboxpeptidase B
Tripsin Arg, lys
Chymotrypsin Trp, Tyr, Phe, Met, Leu
Elastase Ala, Gly, Ser
Carboxypeptidase A
Carboxypeptidase B A.. Ala, Ile, Leu, Val
B.. Arg, Lys
Lippincott’s Illustrated Reviews Biochemistry Denise R. Ferrier Series Editor: Richard A. Harvey, 6th Edition
Absorption of Aminoacids
In enterocytes;
Amino acids, di and tripeptides are absorbed.
Absorption mechanisms of di, tripeptides and aminoacids are different
α-keto glutarate
Glutamine
NH4+
ATP ADP →
Glutamate dehidrogenase
Glutamate NH4+
Glutamine synthatase
NAD (P) + NAD(P)H
Ammonia toxicity
COOH CH2
CH2
C O
COOH COOH
CH2 CH2 CH
COOH
NH2
Glutaminase
NH3
Glutamate is formed as a result of ammonia and alpha keto glutarate reaction
Alpha ketoglutarate↓
The functions of the TCA cycle are disrupted in neurons.
Energy production↓
Glutamate is essential for glutamine production
Glutamate ↓
Glutamate is necessary for GABA synthesis
GABA ↓
Ammonia
concentration↑
Glutamine ↑
Glutamine is
osmotically active in brain astrocytes
Brain Edema
Ammonia toxicity
Ammonia
Sources:
1. Aminoacids 2. Glutamine
3. Bacterial action (Intestine) 4. Amines
5. Pürins and pirimidins
Ammonia Transport
Blood ammonia is quickly cleared by the liver
The release of ammonia from the muscles to the bloodstream occurs in the form of glutamine or alanine.
The release of ammonia from the muscles to the bloodstream occurs in the form of glutamine or alanine.
The main role of the glucose-alanine cycle; is to allow the skeletal muscle to eliminate nitrogen.
The amino acid of alanine plays a role in the non-toxic transport of
ammonia to the liver.
Glucose-Alanine Cycle
Liver Blood stream Muscle
NH4+ Pyruvate
Alanine Alanine
Pyruvate Glutamate
NH4+
Urea Glucose Glucose
REFERENCES
Lippincott’s Illustrated Reviews Biochemistry Denise R. Ferrier Series Editor: Richard A. Harvey, 6th Edition https://www.ncbi.nlm.nih.gov/pubmed/22139560
