Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Protein Metabolism


Published on

Are most abundantly distributed organic compounds.

70 kg man= protein weight constitute 12 kg

Skeleton and connective tissue contains half

Body protein and other half is intracellular.

Published in: Health & Medicine
  • Over the past few days I've been telling you about a NEW 5-second "water hack" that crushes food cravings and melts 62lbs of fat... I know the video is long and you probably don't have time to watch the whole thing, so... I had it transcribed for you, so you can read it whenever you have a few minutes... ➣➣➣
    Are you sure you want to  Yes  No
    Your message goes here
  • What gout treatment options are available to me? ★★★
    Are you sure you want to  Yes  No
    Your message goes here
  • Boy and Girl! Was I wrong! ■■■
    Are you sure you want to  Yes  No
    Your message goes here
  • People laughed at me until I� ◆◆◆
    Are you sure you want to  Yes  No
    Your message goes here
  • NO NO NO... ➤➤
    Are you sure you want to  Yes  No
    Your message goes here

Protein Metabolism

  1. 1. WELCOME Tapeshwar Yadav (Lecturer) BMLT, DNHE, M.Sc. Medical Biochemistry
  2. 2. Tapeshwar Yadav (Lecturer) BMLT, DNHE, M.Sc. Medical Biochemistry
  3. 3. Introduction  Are most abundantly distributed organic compounds.  70 kg man= protein weight constitute 12 kg  Skeleton and connective tissue contains half  Body protein and other half is intracellular.
  4. 4.  Protein Turnover:  The total amount of protein in the body remains constant (i.e Rate of protein synthesis is constnt)  Is equal to protein degradation.  This process is called as protein turnover.  300 to 400 Gm/day.
  5. 5.  Rate turn over  Half-lives Proteins Hours/Days Digestiive Enzymes & Plasma proteins. Months/years Collagen.(Structural Proteins) Proteins rich in Proline, Glutamate, Serine and threonine are rapidly degraded and short half-lives
  6. 6.  AminoAcid pool  Amino acids released by dietary & tissue Protein  Mix with free amino acids of body = Constitutes=100 gm.  Glutamate,Glutamine - 50 %  Essential amino acids - 10%.  Remaining Non-Essential Amino Acids.
  7. 7.  Proteins rich in Proline,Glutamate,Serine and Threonine are rapidly degraded and have short half- lives.  AMINO ACID POOL: -Amino acids released by 1.Dietary and 2.Tissue protein.
  8. 8.  There is no storage form of amino acids like Glycogen and Triglycerides.  Excess intake of proteins(Amino acids) are metabolised then oxidised to provide energy or converted to glucose or fat.  Amino groups lost as Urea→Excreted.
  9. 9.  Body Dietary Synthesis Protein Protein Non-Essential AA Body Protein Porphyrins Purines & Pyrimidins Creatine Neurotransmitters UREA Glucose CO₂ Fattyacids Glycogen Ketone Bodies Steroids AMINO ACID POOL 100 G
  10. 10. Digestion of Dietary Proteins  Proteins are too large to be absorbed by intestine and must be hydrolysed to yield amino acids,which can beabsorbed.  Proteolytic enzymes responsible for degrading proteins are produced by 3 different organs: Stomach,Pancreas and Small intestine.
  11. 11.  PROTEIN DIGESTION:- Dietary protein-50-100 gm/day.  30-100gm/Day- Endogenous protein from digestive enzymes.  Dietary proteins are denatured on cooking.
  12. 12.  Proteins are degraded by hydrolases which cleave peptide bonds known as peptidases. Exopeptidases and endopeptidases. EXOPEPTIDASES ENDO PEPTIDASES 1.Carboxy peptidases. Aspartate Proteinase 2.Amino peptidases. Eg:- Trypsin 3.Tripeptidyl peptidases. Serine Proteinases 4.Dipeptidyl peptidases. Eg:-Trypsin 5.Dipeptidase Cysteine Proteinases Eg:-Papain Metallo Proteinases Eg:-Metal-ion
  13. 13.  DIGESTION @ Stomach  HCl , pH=2, Due to HCl, secreted by parietal cells.  Denature Protein  Destroys microorganisms.  Pepsin = Pepsinogen HCl Pepsin.
  14. 14.  ABSORPTION :- Occurs in small intestine of infants immediately after birth. This process is known as PINOCYTOSIS.  Direct transfer is useful for taking up of maternal γ Globulins.
  15. 15.  ADULTS:-Direct transfer of 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.
  16. 16.  Abnormality of protein digestion:-HARTNUP’S disease is due inability of intestinal absorption of neutral amino acids.  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 for protein synthesis.  20-25% for urea.
  17. 17.  Proteins are 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 ↑.
  18. 18. 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.  The enzymes catalyzing the reaction as a group are known as AMINO TRANSFERASES.  All amino Transferases require coenzyme – Pyridoxal phosphate-B6.
  19. 19. Alanine KetoGlutarate AminoTransferase(GPT) Pyruvate Glutamate(GLU) Aspartate KetoGlutarate AminoTransferase(GOT) OxaloAcetate Gutamate (GLU)
  20. 20.  All amino acids ,except LYSINE,THREONINE participate in Transmination.  The reaction is Cytoplasmic and takes place in liver.  Transminases are induced by Glucocorticoids which promotes Gluconeogenesis.
  21. 21.  Clinical significance:- ↑Levels in plasma indicates damage to cells rich in these enzymes.  SGPT↑ :- Toxic Hepatisis. Viral Hepatisis Cirrhosis.  SGOT:- Myocardial infarction,Pulmonary disorders.  Function:- Transmination is useful synthesis of Non- Essential Aminoacids.  Major oxidative deamination is catalysed. Glutamate DeHydrogenase (GDH) It is a mitochondrial enzyme in Liver.
  22. 22. OXIDATIVE DEAMINATION:- Mammals=L-AminoAcid Oxidase=FMN Plants&Microorganisms =D-Aminoacid Oxidase=FAD All amino acids first transaminated to glutamate and then deaminated. Then coupling of Transamination & Deamination is called as Transdeamination.
  23. 23.  All amino acids, amino groups are funnelled into glutamate. High Protein Diet = High Ammonia formation. When energy levels are low amino acid degradation by GDH is High,Provides α-KG for TCA cycle. Allosteric regulators= ATP,GTP=Inhibitors ADP,GDP=Activators
  24. 24.  NON-OXIDATIVE DEAMINATION 1.Enzymes that acts as dehydratases forms corresponding keto acid and ammonia. Threonine Deaminase Keto Butyrate +NH₃ 2.Transulfuration: Cysteine Pyruvate+NH₃ + H₂S 3.Histidine undergoes non-oxidative deamination by histidase. 4.Glutamine Glutaminase* Glutamate + NH₃ Aspargine Asparginase* Aspartate + NH₃. These enzymes have been utilized as Anti-Tumor Agents. *Acts as anti tumor agents
  25. 25. Metabolism of Ammmonia:-  SOURCES OF AMMONIA :- Amino acids Synthesises Protein, Protein degraded to Amino acids. From Liver : a) Transamination b) Oxidative deamination From Kidney : Glutaminase reaction From Intestine : By Bacterial action From Diet : Amines From Catabolism : Purines (Adenine) Pyrimidines (Cytosine) From Non–oxidative: Deamination : Aminoacids
  26. 26. UTILIZATION OF AMMONIA:-  Glutamate+ Ammonia Glutamine.  Glutamine synthetase- Liver, Brain and Kidney.  Brain :- Major mechanism for removal 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 amino acids.
  27. 27. 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
  28. 28. TRANSPORT OF AMMONIA:-  Ammonia is constantly produed in tissues.  Plasma ammonia - 10-20 μg /dl.  Elevated levels cause symptoms of ammonia intoxication.  SYMPTOMS:-Tremor, Slurring of speech, Blurring of vision→Coma and death.
  29. 29.  HYPER AMMONEMIA:-  1. Acquired.  2. Hereditary.  ACQUIRED HYPER AMMONEMIA:- Cirrhosis of liver caused by Alcoholism. Hepatitis. Biliary obstruction-Resulting formation collateral circulation where portal blood enterssystemic circulation.
  30. 30. HEREDITARY HYPER AMMONEMIA:- All inherited deficiencies of UREA CYCLE ENZYMES result in HYPER AMMONEMIA. Prevalence is 1 in 30000 individuals.
  31. 31. 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
  32. 32.  Urea cycle is also called as Krebs-Henseleit or Ornithine cycle.  Site: Liver  Urea synthesized in Liver, released into Blood, cleared by Kidneys.  Urea cycle is devided into Five steps.
  33. 33. 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.
  34. 34.  Step 2. Formation of Citrulline Carbamoyal phosphate +Ornithine Ornithine Transcarbamoylase Citrulline + Pi  Ornithine trans carbmoylase is also a Mitochondrial enzyme
  35. 35. This step onwards the reactions occurred in CYTOPLASM  Step3- Formation of Argininosuccinate.  Citrulline + Aspartate + ATP Argininosuccinate synthase Argininosuccinate + AMP + PPi
  36. 36.  Step 4. Formation of Arginine. Argininosuccinate Argininosuccinase Arginine + Fumarate  Step 5. Formation of Urea. Arginine + H₂O Arginase Ornithine + Urea.
  37. 37. 2.Regulation of Urea Cycle : a) Carbamoyl Phosphate Synthase-1: Allosteric activator –N-acetylglutamate. More glutamate, 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.
  38. 38. 3 Energetics of Urea cycle: ATP UTILIZED Carbamoyal phosphate synthase -2ATP Argininosuccinate synthase -2ATP ATP GENERATED Fumarate- Malate- MDH +3ATP Net Energy expenditure -1ATP
  39. 39.  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 protein diet b) Increased protein catabolism –starvation c) Gastro-intestinal haemorrhage.
  40. 40.  Renal causes a) Chronic renal failure B) Acute glomerulonephritis c) Nephroscelerosis.  Postrenal causes a) Renal stone B) Prostate enlargement c) Malignant stricture
  41. 41.  Decreased Blood Urea Levels:  a) Low protein diet.  b) Liver diseases  c) Water retention.
  42. 42.  DISORDERS OF UREA CYCLE:  a) Hyperammonemia - Type I -Enzyme Defeciency - CPS 1 -Symptoms - Increased blood ammonia (↑ NH₄) Mental retardation Autosomal recessive .
  43. 43.  HYPER AMMONEMIA Type II  Enzyme deficiency –Ornithine transcarbamoylase  ↑ NH₃ in Blood; Glutamine ↑ in C.S.F, urine, blood.  X-Linked inheritance.  Orotic aciduria, Mental retardation.
  44. 44.  CITRULLINEMIA:-  Argininosuccinate synthetase deficiency. Citrulline↑ in blood, urine (1- 2 gm/day) . Autosomal recessive.  ARGININO SUCCINIC ACIDURIA:- Absence of Arginino succinase. Argininosuccinic acid ↑ blood and urine. TRICHORRHEXIS NODOSA = Friable, brittle ,tufted hair.
  45. 45.  HYPER ARGININEMIA:-  Arginase deficiency.  Arginine in blood and CSF ↑.  Incidence one in 1,00,000 individuals.