3. Introduction
⚫Are most abundantly distributed organic compounds.
⚫70 kg man= protein weightconstitute 12 kg
⚫Skeletonand connective tissue contains half
⚫Body protein and other half is intracellular.
4. ⚫Protein Turnover:
⚫The total amountof protein in the body remains
constant (i.e Rateof protein synthesis isconstnt)
⚫Is equal to protein degradation.
⚫This process is called as protein turnover.
⚫300 to 400 Gm/day.
6. ⚫AminoAcid pool
⚫Aminoacids released bydietary & tissue Protein
⚫Mix with freeaminoacids of body = Constitutes=100
gm.
⚫Glutamate,Glutamine - 50 %
⚫Essential aminoacids - 10%.
⚫Remaining Non-Essential Amino Acids.
7. ⚫Proteins rich in Proline,Glutamate,Serine and
Threonineare rapidly degraded and have short half-
lives.
⚫ AMINO ACID POOL: -Aminoacids released by
1. Dietary and 2.Tissue protein.
8. ⚫There is no storage form of aminoacids like
Glycogen and Triglycerides.
⚫Excess intake of proteins(Amino acids) are
metabolised then oxidised to provideenergy or
converted toglucoseor fat.
⚫Aminogroups lostas Urea→Excreted.
10. ⚫Digestionof Dietary Proteins
⚫Proteins are too large to be absorbed by
intestine and must be hydrolysed toyield
aminoacids,which can beabsorbed.
⚫Proteolyticenzymes responsible fordegrading
proteins are produced by 3 different organs:
Stomach,Pancreas and Small intestine.
11.
12.
13. ⚫PROTEIN DIGESTION:- Dietary protein-50-100
gm/day.
⚫30-100gm/Day- Endogenous protein from digestive
enzymes.
⚫Dietary proteinsaredenatured on cooking.
14. ⚫ Proteins are degraded by hydrolases which
cleave peptide bonds known as peptidases.
Exopeptidasesand endopeptidases.
EXOPEPTIDASES
1. Carboxy peptidases.
2.Amino peptidases.
3.Tripeptidyl peptidases.
4.Dipeptidyl peptidases.
5.Dipeptidase
ENDO PEPTIDASES
Aspartate Proteinase
Eg:- Trypsin
Serine Proteinases
Eg:-Trypsin
Cysteine Proteinases
Eg:-Papain
Metallo Proteinases
Eg:-Metal-ion
15. ⚫DIGESTION @ Stomach
⚫HCl , pH=2, Due to HCl, secreted by parietal cells.
⚫Denature Protein
⚫Destroys microorganisms.
⚫Pepsin = Pepsinogen HCl Pepsin.
16. ⚫ABSORPTION :- Occurs in small intestineof infants
immediately after birth. This process is known as
PINOCYTOSIS.
⚫Direct transfer is useful for taking up of maternal
γ Globulins.
17. ⚫ADULTS:-Direct transferof intact protein (or) poly
peptide in body elicits Antibody formation(Food
allergy).
⚫NONTROPICAL SPURE:-Tripeptde digestionof wheat
Glutemate stimulates antibody production.
⚫CELIAC DISEASE in children same phenomena has
been obsreved.
18. ⚫Abnormality of protein digestion:-HARTNUP’S
disease is due inabilityof intestinal absorption of
neutral aminoacids.
⚫PROTEIN TURNOVER:-Continuous degradation and
resynthesis occurs in all cellular proteins.
⚫Adults degrade 1-2% of their body protein
daily(muscle protein).
⚫75-80% are utilized forprotein synthesis.
⚫20-25% forurea.
19.
20. ⚫Proteinsare degraded at varying rates.
⚫1.High mean rates of protein degradation occurs in
uterine tissue during pregnacy.
⚫2.During strvation ,skeletal muscle protein
degradation is ↑.
21.
22.
23. ⚫TRANSMINATION is defined as a process in
which amino group is transferred from an Aminoacid
to Ketoacid to form an corresponding Aminoacid that
itself is forming Ketoacid with out liberation of
ammonia.
⚫Theenzymes catalyzing the reaction as a groupare
known as AMINO TRANSFERASES.
⚫All amino Transferases requirecoenzyme –
Pyridoxal phosphate-B6.
25. ⚫All aminoacids ,except LYSINE,THREONINE
participate in Transmination.
⚫The reaction is Cytoplasmicand takes place in
liver.
⚫Transminases are induced by Glucocorticoids
which promotes Gluconeogenesis.
26. ⚫Clinical significance:- ↑Levels in plasma indicates
damage tocells rich in these enzymes.
⚫SGPT↑ :- Toxic Hepatisis.
Viral Hepatisis
Cirrhosis.
⚫SGOT:- Myocardial infarction,Pulmonary disorders.
⚫Function:- Transmination is useful synthesis of
Non- Essential Aminoacids.
⚫Majoroxidativedeamination is catalysed.
Glutamate DeHydrogenase (GDH)
It is a mitochondrial enzyme in Liver.
30. All aminoacids, aminogroups are funnelled into
glutamate.
High Protein Diet = High Ammonia formation.
When energy levels are low aminoacid degradation
by GDH is High,Provides α-KG forTCA cycle.
Allosteric regulators=
ATP,GTP=Inhibitors
ADP,GDP=Activators
31. ⚫NON-OXIDATIVE DEAMINATION
1. Enzymes that acts as dehydratases forms
correspondingketoacid and ammonia.
Threonine Deaminase Keto Butyrate +NH₃
2.Transulfuration:
Cysteine Pyruvate+NH₃ + H₂S
3. Histidine undergoes non-oxidative deamination
by histidase.
4.Glutamine
Aspargine
Glutaminase*
Asparginase*
Glutamate + NH₃
Aspartate + NH₃.
These enzymes have been utilized as Anti-Tumor
Agents.
*Acts as anti tumor agents
32. Metabolism of Ammmonia:-
⚫SOURCES OF AMMONIA :-
Aminoacids Synthesises Protein,
Protein degraded to Aminoacids.
From Liver : a) Transamination
b) Oxidativedeamination
From Kidney : Glutaminasereaction
From Intestine : By Bacterial action
From Diet : Amines
From Catabolism : Purines (Adenine)
Pyrimidines (Cytosine)
From Non–oxidative: Deamination : Aminoacids
33. UTILIZATION OF AMMONIA:-
⚫ Glutamate+ Ammonia Glutamine.
⚫ Glutamine synthetase- Liver, Brain and Kidney.
⚫ Brain :- Major mechanism forremoval of
Ammonia is Glutamate formation.
⚫αKG+NH3+NADPH+H⁺ Glutamate+NADP⁺
⚫Glutamate may be considered as a major transport
form of NH₃ from tissue to liver.Concentration of
Glutamate in blood is 10 times more than other
aminoacids.
34. 3 Important disposal route of ammonia is formation
of Urea.
End product Amino Nitrogen
In mammals is Urea - Ureotelic.
Fishes is Ammonia - Ammonotelic.
Birds & Reptiles is Uric acid - Uricotelic
35. TRANSPORT OF AMMONIA:-
⚫Ammonia is constantly produed in tissues.
⚫Plasma ammonia - 10-20 μg /dl.
⚫Elevated levelscause symptoms of ammonia
intoxication.
⚫SYMPTOMS:-Tremor, Slurring of speech, Blurring of
vision→Comaand death.
36. ⚫HYPER AMMONEMIA:-
⚫1. Acquired.
⚫2. Hereditary.
⚫ACQUIRED HYPER AMMONEMIA:-
Cirrhosis of livercaused by Alcoholism.
Hepatitis.
Biliary obstruction-Resulting formation
collateral circulation where portal blood
enterssystemic circulation.
37. HEREDITARY HYPER AMMONEMIA:-
All inherited deficienciesof UREA CYCLE ENZYMES
result in HYPER AMMONEMIA.
Prevalence is 1 in 30000 individuals.
38.
39. UREA CYCLE
⚫1.Enzymes of Urea cycle
⚫2.Regulation of Urea cycle
⚫3.Energetics of Urea cycle
⚫4.Clinical significance of blood Urea
⚫5.Disorders of Urea cycle
40. ⚫Urea cycle is also called as Krebs-Henseleit or
Ornithinecycle.
⚫Site: Liver
⚫Urea synthesized in Liver, released into Blood, cleared
by Kidneys.
⚫Urea cycle is devided into Fivesteps.
41.
42. Two nitrogen atoms of urea are derived from
ammonia and alpha amino group of aspartic
acid.
One mol of urea synthesis requires 4 mol of ATP.
Step 1 in Mitochondria:-
CO₂ + Ammonia + 2 ATP Carbamoyl
Phosphate+2ADP+PPi
Carbamoyl phosphate synthase 1(CPS-1)
It is a Mitochondrial enzyme,
Allosteric activator is N-Acetyl Glutamate.
43. ⚫Step 2. Formation of Citrulline
Carbamoyal phosphate +Ornithine
Ornithine Transcarbamoylase
Citrulline + Pi
⚫Ornithine trans carbmoylase is also a Mitochondrial
enzyme
44. This step onwards the reactions occurred in
CYTOPLASM
⚫ Step3- Formation of Argininosuccinate.
⚫ Citrulline + Aspartate + ATP
Argininosuccinate synthase
Argininosuccinate + AMP + PPi
46. 2.Regulation of Urea Cycle :
a) Carbamoyl Phosphate Synthase-1:
Allosteric activator –N-acetylglutamate.
Moreglutamate, more N-acetylglutamate,
more CPS-1 activity, leads more Urea synthesis.
b)During starvation, Urea cycle enzyme activities are
increased to meet the demands of increased rate of
protein catabolism.
47. 3 Energetics of Urea cycle:
-2ATP
-2ATP
ATP UTILIZED
Carbamoyal phosphate synthase
Argininosuccinate synthase
ATP GENERATED
Fumarate- Malate- MDH +3ATP
Net Energyexpenditure -1ATP
48. ⚫ Clinical significance of Blood Urea:
Normal Blood Urea = 15 - 40 mgs %
Normal Urine Urea = 15 - 30 grams/day
Increased Blood Urea levels:
Prerenal causes
a) High proteindiet
b) Increased protein catabolism –starvation
c) Gastro-intestinal haemorrhage.
49. ⚫Renal causes
a) Chronic renal failure
B) Acute glomerulonephritis
c) Nephroscelerosis.
⚫Postrenal causes
a) Renal stone
B) Prostateenlargement
c) Malignant stricture
50. ⚫Decreased Blood Urea Levels:
⚫a) Low protein diet.
⚫b) Liver diseases
⚫c) Water retention.
51. ⚫DISORDERS OF UREA CYCLE:
⚫a) Hyperammonemia - Type I
-Enzyme Defeciency - CPS 1
-Symptoms - Increased blood ammonia (↑ NH₄)
Mental retardation
Autosomal recessive .
52. ⚫HYPER AMMONEMIA Type II
⚫Enzymedeficiency –Ornithine transcarbamoylase
⚫↑ NH₃ in Blood; Glutamine ↑ in C.S.F, urine, blood.
⚫X-Linked inheritance.
⚫Oroticaciduria, Mental retardation.
