1. Protein metabolism part 1 Dr.basima

2. body.Adult requires 70 -100 gm protein / day. Protein Turnover;
INTRODUCTION;
Dietary proteins are the primary sources of the nitrogen that is metabolized by the
body.Adult requires gm protein / day.
Protein Turnover;
Most proteins in the body are constantly being synthesized and then degraded which leads to the hydrolysis and resynthesis of 300 to 400 gm/day. The turnover is ↑ in infancy and ↓ with age advance. .

3. NITROGEN BALANCE;
evaluate the relationship between the nitrogen intake (in the form of protein) and nitrogen excretion.
1- Nitrogen Equilibrium;the rate of body protein synthesis is equal to the rate of degradation.
2- Positive Nitrogen Balance;nitrogen intake > nitrogen excretion his occurs in growing infants and pregnant women.
3- Negative Nitrogen Balance; nitrogen intake < nitrogen
excretion, i.e. nitrogen output exceeds input and occurs during serious illness , major injury and trauma, in advanced cancer and following failure to ingest adequate or sufficient high quality protein, e.g. in kwashiorkor and marasmus.
• If the situation is prolonged, it will ultimately lead to death.

4. Digestion and absorption

5. Large peptides + some free A.As Further digested by pepsin
Proteins
Parietal cells
Gastric HCL
1st
Denatured proteins
Chief cells
HOW?
Endopeptidase with broad
Specificity (cleaves the
internal peptide bonds in
which the carboxylic group
is of aromatic A.As or leucine)
Pepsinogen
Pepsin
Inactive zymogen
Active enzyme
then
Rennin in infants Ca
Milk
caseinogen
Soluble casein
Ca paracaseinate
(milk clot)
Denaturation
Importance?
Large peptides + some free A.As
Further digested by pepsin
and other proteases

6. Large peptides + some free A.As Smaller peptides + free A.As
Pancreatic endopeptidases including
Intestinal cells
*Trypsinogen Trypsin
(inactive) (active)
*Chymotrypsinogen Chymotrypsin
(inactive) (active)
*Proelastase Elastase
*Collagenase
Cleaves peptide bonds in which the COOH
is of Basic A.As (arginine and lysine)
is of Aromatic A.As or leucine.
is of small non polar A.As (A.As with small
uncharged R as glycine, alanine & serine)
Catalyzes the hydrolysis of collagen
enteropeptidase
Smaller peptides + free A.As

7. In infants, Ig A in the clostrum of milk is
absorbed without digestion by pinocytosis
giving immunity to the babies
Intestinal lumen
Intestinal cell
Blood
IgA
IgA
[gA
[gA
[gA

8. ► Carrier protein transport system
A.As resulting from protein digestion
are absorbed from the small intestine by:
■ passive transport mechanism (For D-A.As).
■ Active transport mechanism (For L-A.As and dipeptides):
► Carrier protein transport system
( sodium – amino acid carrier system ).
► Glutathione transport system
(γ-glutamyl cycle)

9. Carrier protein transport system ( sodium – amino acid carrier system )
Intestinal lumen K+
Na+
A.A.
Na+
A.A
ADP+Pi
Cell membrane
Na/K ATPase
Carrier
ATP
Intestinal cell K+
Na+
A.A
Cytoplasm
Portal blood
A.A.

10. Glutathione transport system (γ-glutamyl cycle)
A.A.
NH2—CH—COOH
γ-glutamyl transpeptidase(transferase) (GGT)
Cell membrane
CO-NH-CH-COOH
CH2 R
γ-glutamyl- cysteinylglycine
cysteinylglycine
CH2
ADP+Pi
CH-NH2
glutathione
synthetase
dipeptidase
COOH
ATP
γ-glutamyl A.A
glycine
γ-glutamyl- cysteine
γ-Glutamyl
cyclotransferase
A.A.
ADP+Pi
γ-Glutamylcysteine
synthetase
cysteine
5-oxoproline
ATP
H2C CH2
Glutamic acid
Oxoprolinase
H2O
O=C
CH-COOH
ADP+Pi
ATP N I H

12. ► 3 ATP molecules are utilized for the transfer of one a. a
► 3 ATP molecules are utilized for the transfer of one a.a. ►Clinical notes: ■The blood conc. of GGT enzyme is increased in cholestasis & chronic alcholism ( so used as a liver function test). ■Oxoprolinuria: Inherited deficiency of glutathione synthetase enzyme , leading to increase levels of 5 oxoproline in blood &urine acidosis & neurological damage .

14. Enter in the formation of A.A. pool
Fate of absorbed A.As
Enter in the formation of A.A. pool

16. CATABOLISM OF AMINO ACIDS
following stages:
1. The removal of α-amino group in the form of
ammonia by following reactions:
i-Transamination by the enzyme aminotransferase also called transaminases.
Most amino acids undergo transamination reaction except lysine, threonine, proline and hydroxyproline.
ii. Deamination may be;
a. Oxidative deamination is by glutamate dehydrogenase or amino acid oxidase.
b. Nonoxidative deamination is by amino acid dehydratase.
2. Disposal of ammonia in the form of urea in the liver by reactions of the urea cycle.
3. Disposal (catabolism) of the remaining carbon skelton of amino acid to carbon dioxide and water by reactions of citric acid cycle.

20. METABOLIC FATE OF AMMONIA
NH4+ is produced in most tissues. NH4+ is extremely toxic, it is immediately converted to nontoxic metabolites to urea. Ammonia is transported to the liver.
Two mechanisms are available in humans for the transport of ammonia from the peripheral tissues to the liver.

21. Transport of Ammonia in the Form of Glutamine,In many tissues (liver, kidney and brain), ammonia is enzymatically combined with glutamate to yield glutamine by the action of glutamine synthetase..
Transport of ammonia in the form alanine from muscles to the liver through glucose alanine cycle.

22. urea cycle

24. Significance of Urea Cycle
• The toxic ammonia is converted into nontoxic urea. It disposes off two waste products, ammonia and CO2.
• It forms semi essential amino acid, arginine. It participates in the regulation of blood pH, which is depends upon the ratio of dissolved CO2, e.g H2CO3toHCO3.
• Ornithine is a precursor for the formation of polyamines like, spermidine and spermin .
Regulation of Urea Cycle
• Carbamoyl phosphate synthetase-I is an allosteric regulatory enzyme of urea cycle, which is activated by N-acetylglutamate (NAG). NAG is synthesized from acetyl-CoA and glutamate by NAG-synthase to activate CPS-I.

25. Ammonia Intoxication
Symptoms of ammonia intoxication includes:
– An impaired function of the brain
– Tremor
– Ataxia
– Convulsions
– Lethargy
– Nausea
– Vomiting
– Slurred speech
– Blurred vision
– In severe cases, coma and death. The toxic effect of NH4+ may be due to:
↓in the formation of ATP by citric acid cycle because of diversion of excessive
amounts of α-ketoglutarate from citric acid cycle intermediates to form glutamate and glutamine (to detoxify ammonia) in the brain and ↓the rate of oxidation of glucose, the major fuel of the brain. By ↑ formation of GABA(Ƴ-amino butyric acid) from glutamate leads to impaired neural transmission process. One more possibility is that ↑ levels of glutamine, formed from NH4+and glutamate produce osmotic effect that leads directly to swelling of the brain.

26. Metabolic Inborn Errors of Urea Cycle
5 disorders associated with each of the 5 enzymes of urea cycle.
non-toxic urea, all defects in urea synthesis result in hyperammonemia and ammonia intoxication. more severe when the metabolic block occurs at reaction I or II, since it accumulates ammonia itself.
Clinical symptoms.
Ammonia intoxication
Protein induced vomiting
Intermittent ataxia
Irritability
Lethargy
Mental retardation

28. CATABOLISM OF CARBON SKELETON OF AMINO ACIDS;
(20 ) amino acids are convered into 7 products.
• Pyruvate
• Acetyl-CoA
• Acetoacetyl-CoA
• α-Ketoglutarate
• Succinyl-CoA
• Fumarate
• Oxaloacetate.
All these enter the citric acid cycle and are used for the synthesis of glucose or lipid or in the production of energy through their oxidation to CO2and H2O.• Amino acids that are degraded to acetyl-CoA or acetoacetyl-CoA are termed ketogenic• Amino acids, that are degraded to pyruvate, α-ketoglutarate, succinyl-CoA, fumarate or oxaloacetate,are termed glucogenic.•

30. Metabolic Importance of Glycine ; : 1
Metabolic Importance of Glycine ; : 1. Synthesis of heme: Glycine along with succinyl CoA serves as a precursor for heme synthesis. 2. Synthesis of glutathione: the formation of biologically important peptide,glutathione (γ-glutamyl-cysteinyl-glycine). 3. Formation of purine ring: It provides C4, C5and N7of the purine ring.

31. 4. Formation of bile acids:cholic acid are conjugated with glycine to form glycocholic acid and glycochenodeoxy cholic acid respectively. Conjugation lowers the pK of the bile salts, making them better detergents. 5. Glycine is involved in detoxification reactions. 6. Synthesis of creatin: Creatin is present in muscle and brain tissue as the high energy compound creatin phosphate. 7. Collegen formation: In collagen glycine occurs at every third position of a chain of the triple helix. 8. Glycine is glucogenic amino acid, synthesis of glucose. 9. Glycine is constituent of various tissue proteins, hormones and enzyme.

32. Thank you dr.basema