Basic structures of protein and protein metabolism-Student Copy PDF

Basic structures of protein and Protein metabolism Dr Moe Thida Kyaw Lecturer Human Biology Department [email protected] Inspir...

Basic structures of protein and Protein metabolism Dr Moe Thida Kyaw Lecturer Human Biology Department [email protected] Inspire Empower Elevate  1. List the various functions of proteins 2. Describe amino acids and its role in the protein structure Learning 3. Differentiate between globular and fibrous proteins outcome 4. Explain why the structure of the protein is important for its function (haemoglobin as an s example). 5. Describe breakdown, synthesis of amino acids 6. Explain how excess nitrogen in secreted from the body 2  Proteins are organic compounds made of amino What are acids arranged in a linear proteins? chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. Biological Roles of Proteins 1. Building materials - Growth and maintenance - Muscle tissue - Bone tissue - Ligaments and tendons - Blood - Skin - Hair, Nails, Scar tissue - GI tract cells - Repair - clotting factors - Scar tissue (wound healing) 2. Proteins as enzymes Enzymes are usually composed of a protein. They act as catalysts, allowing reactions to occur more quickly and efficiently. 3. Proteins as hormones Insulin – Polypeptide hormone 4. Regulate fluid balance 5. Regulates acid – base Outside balance Plasma membrane Eg. Haemoglobin Inside Transporter Enzyme Cell surface receptor 6. Transporters and Receptors - In Blood - Albumin, Globulins, Cell surface Attachment to the identity Cell adhesion cytoskeleton Haemoglobin marker - In cells Membrane Protein Functions - Transport of molecules - Hormone receptors 7. Immunoglobulins/Antibodi es Knowledge check-1 Which type of protein is involved in muscle contraction? (A) Actin (B) Hemoglobin (C) Collagen (D) Thyroxin  1. List the various functions of proteins 2. Describe amino acids and its role in the protein structure Learning 3. Differentiate between globular and fibrous proteins outcome 4. Explain why the structure of the protein is important for its function (haemoglobin as an s example). 5. Describe breakdown, synthesis of amino acids 6. Explain how excess nitrogen in secreted from the body 10  Protein Structure Why study structure?  Structure helps us understand function  Many disorders are due to aberrant protein structure Sickle cell anemia Can aid in design of therapeutics  Disruption of structure causes disruption of function Denaturation  Amino acid: Basic unit of protein Proteins are polymers made out by the condensation of amino-acids  All amino-acids have an amino group and a carboxylic group connected through a single carbon (called alpha-carbon, shown in blue)  The 20 amino-acids differ from one another in the chemical structure of the chain connected to the alpha carbon (called side- chain, shown as a red R) Chemical Structure of the 20 Natural Amino acids - Aliphatic - Aromatic - Polar - Sulfur-containing - Charged (Positive, Negative) These properties are crucial to provide the ability to fold into specific 3D structures. Each of the 20 amino-acids has a common name, a three-letter acronym and a 1 letter acronym. Peptide Formation  Structure of Proteins Sequence of Recurring AAs structural patterns 3D folding of Arrangement PPs of two or more PPs in space Sickle cell anaem ia HbS disease (Sickle Cell Anemia)nonpolar Val is substituted for Glu Sickled RBCs cause infarction because the rigid polymer of HbS makes the sickled cells less deformable than the non-sickled cells and, therefore, less able to move through blood vessels. This can cause a blockage that obstructs the delivery of O2 Knowledge check-2 Which type of bond stabilizes the secondary structure of proteins? (A) Covalent bond (B) Ionic bond (C) Hydrogen bond (D) Van der Waals forces  (1) Which level of protein structure depicted can be correctly described as the “three-dimensional shape of a folded polypeptide Knowledge chain”? Check - Flash (2) Answer the followings: (i) At which level of protein Card-1 structure that mutations (insert, delete, or replace amino acids change) occurs? (ii) Describe the consequences of the above changes.  1. List the various functions of proteins 2. Describe amino acids and its role in the protein structure Learning 3. Differentiate between globular and fibrous proteins outcome 4. Explain why the structure of the protein is important for its function (haemoglobin as an s example). 5. Describe breakdown, synthesis of amino acids 6. Explain how excess nitrogen in secreted from the body 19 Differences between fibrous and globular proteins Fibrous protein Globular protein Purpose of Structural –these Functional – these proteins Proteins proteins helps to maintain carry out a specific biological cell shape by providing a function in the body scaffolding Shape of long and narrow spherical in shape Proteins Sequence of Amino acid sequence is Amino acid sequence is irregular A.A repetitive in nature Resilience Less sensitive to factors More sensitive to temperature such as changes in and pH temperature and pH Solubility Insoluble in water Soluble in water Examples Keratin, collagen, Haemoglobin, myoglobin, elastin, fibrin insulin, enzymes https://byjus.com/biology/difference-between-globular-and-fibro us-protein/  1. List the various functions of proteins 2. Describe amino acids and its role in the protein structure Learning 3. Differentiate between globular and fibrous proteins outcome 4. Explain why the structure of the protein is important for its function s (haemoglobin as an example). 5. Describe breakdown, synthesis of amino acids 6. Explain how excess nitrogen in secreted from the body 21 Structure of Proteins The structure of proteins are specific. The specific structure allows to protein to perform a specific function. Loss of structure means loss of function Protein shape and function Example: - Hemoglobin found in the red blood cell - carries oxygen from the lungs to the tissues - returns carbon dioxide and protons from the tissues to the lungs The formation of the tetrameric quaternary structure of hemoglobin, but not of myoglobin, is determined by hydrophobic and hydrogen-bonding interactions and salt bridges between amino acid residues on the surface of hemoglobin monomers. Knowledge check-3 Which of the following features of haemoglobin is crucial for its ability to carry oxygen? (A)Four polypeptide chains (B)Heme groups containing iron (C)Globular shape (D)High molecular weight  1. List the various functions of proteins 2. Describe amino acids and its role in the protein structure Learning 3. Differentiate between globular and fibrous proteins outcome 4. Explain why the structure of the protein is important for its function (haemoglobin as an s example). 5. Describe breakdown, synthesis of amino acids 6. Explain how excess nitrogen in secreted from the body 25 OVERVIEW OF PROTEIN & NITROGEN Body Protein METABOLISM Protein Turn Over N2 containing Dietary Protein Amino acid Pool compounds; Heme, 30-60 mg/dl Melanin, ect Kidney Catabolism of amino acids NH3 -Keto acids (Common Metabolic Pool) Aminoacid uria Urea Glucose or Ketone bodies Rate of Protein Turnover  Varies widely for individual proteins Short-lived Proteins (regulatory proteins & misfolded proteins ) rapidly degraded, having half-lives measured in minutes or hours. Long-lived Proteins Majority of proteins of the cell are long-lived, with half-lives of days or hours. Structural proteins, such as collagen, are metabolically stable, & have half-lives measured in months or years. Nitrogen balance The normal state in the adult, occurs when degradation of body protein equals synthesis of new protein. Negative nitrogen balance : degradation of body protein > synthesis of new protein More nitrogen is excreted than ingested. It results from an inadequate amount of protein in the diet or from the absence of one or more essential amino acids. (e.g. acute/chronic illness, convalescence, prolong starvation) Positive nitrogen balance : degradation of body protein < synthesis of new protein Catabolism of Amino acid H Catabolism + NH3-C-COO- of carbon skeleton R Catabolism of Amino Common Metabolic group Pool (4 steps) Pyruvate Acetyl CoA ,Acetoacetyl 1. Transamination CoA 2. Oxidative -ketoglutarate deamination Succinyl CoA Fumarate 3. Ammonia transport Oxaloacetate 4. Urea cycle Glucose Ketone Both Rest Leu, Lys Phe Ile, Tyr, Trp Step 1. Transamination: Funneling of Amino Acids to Glutamate d Lys, Thr o aci  -amino m i n acid -a - a m inoac id Transamination GLUTAMATE  Enzymes involved in Transamination Transamination is catalyzed by Aminotransferases Found in the cytosol & mitochondria of all cells (especially in the liver, kidney, intestine, & muscle) Two important enzymes: 1)Alanine aminotransferase (ALT) 2)Aspartate aminotransferase (AST)  Pyridoxal phosphate (Vit B6) acts as coenzyme. Step 2. Oxidative Deamination of Amino Acids  Enzyme: Glutamate dehydrogenase  present in Liver and kidneys  The final reaction which removes the amino groups from all amino acids.  Products of deamination reactions are (1) α-ketoglutarate (can enter the TCA cycle) (2) Ammonia (a source of nitrogen in urea synthesis)  About 50 – 70 g of amino acids are deaminated per day.  Step 3. Transport of Ammonia to the liver Ammonia is highly toxic – even minute quantities can produce CNS toxicity. It is vital to efficiently eliminate/detoxify the ammonia generated. Disposal of ammonia involves its transport from the peripheral tissues to the liver for its ultimate conversion to urea. Two mechanisms are available in humans : 1. Trapping of ammonia by Glutamate (Glu) to form Glutamine (Gln) & transport of glutamine to the liver & final conversion to urea 2. Glucose–Alanine cycle : Formation of Alanine (Ala) by pyruvate & alanine is transported by the blood to the liver Step 4. Final Disposal of Ammonia: The Urea Cycle Urea is the major disposal form of amino groups of amino acids , and accounts for 90% of nitrogen-containing compounds in urine.  Source of Nitrogen Atoms of Urea The two nitrogen atoms of urea are derived from two different sources: - one from ammonia - the other directly from the α-amino group of Aspartic acid  Location of Reactions 1) The 1st two reactions take place within the mitochondria 2) The remaining reactions occur in the cytosol  Fate of Urea - Urea diffuse from the Liver and is transported in the blood to the kidneys for filtration and excretion in urine - Some diffuse in the intestine and is cleaved to CO2 & NH3 by bacterial urease The Urea Cycle NH3 + CO2 + 2 ATP CARBAMOYL –P- SYNTHETASE 1 Carbamoyl-P + 2ADP + Pi Mitochondria ORNITHINE TRANSCARBAMOYLASE Matrix Ornithine Citrulline Asp ATP ARGININOSUCCINATE SYNTHETASE Urea AMP + 2Pi ARGINASE Argininosuccinate Arginine Cytoplasm ARGININOSUCCINATE LYASE FUMERATE INTEGRATION OF AMINO ACID, CARBOHYDRATE & FAT METABOLISM R – CH (NH3+) – COO Dietary Proteins Proteins of the – AMINO ACIDS Body Deaminatio n of excess to meet Essential Non- immediate Protein Nitrogenous requiremen ts Tissue Constituents: Amino Nitrogen Neurotransmitters Catecholamines Membrane R – CO – COO – components NH3 Keto Acids Haem Nucleotide bases, etc. Glucogeni Ketogenic Amino c Amino Acids Urea Acetyl CoA Acids Pyruvate or TCA Cycle Urine Components Fat CO2 + CO2 + Glucose H2O H2O (Glycogen) Glucogenic/Ketogenic/Nonessential/Essential Amino Acids  Glucogenic: aa of which catabolism yields pyruvate or one of the intermediates of the TCA cycle  Ketogenic : aa of which catabolism yields either acetoacetate or one of its precursors (acetyl CoA or acetoacetyl CoA)  Non-essential: aa whose carbon skeletons can be synthesized  Essential: aa those cannot be synthesized in the body. Must be obtained from the diet.  Leucine & Lysine are the only exclusively ketogenic amino acids found in proteins.  Conversion of amino acids to Specialized products Tryptophan  Serotonin  Melatonin Histidine  Histamine Glutamate  GABA Serine  Ethanolamine  Choline  Acetylcholine Phenylalanine  Tyrosine  DOPA  Dopamine  Catecholamine DOPA  Dopaquinone  Melanin Tyrosine  T3, T4 Glycine  Heme Arginine, Glycine  Creatine phosphate  Creatinine  Summary  Proteins, which are composed of amino acids, serve in many roles in the body (e.g., as enzymes, structural components, hormones, and antibodies).  Interactions between amino acid residues produce the three-dimensional conformation of a protein, starting with the primary structure, leading to secondary and tertiary structures, and for multi- subunit proteins, a quaternary structure.  Amino acids are used by cells for the synthesis of proteins, which is a dynamic process; proteins are constantly being synthesized and degraded.  After nitrogen is removed from amino acids, the carbon skeletons can be oxidized for energy.  The nitrogen of amino acids is converted to urea in the liver and ultimately excreted by the kidney.  During fasting, muscle protein is degraded and supplies amino acids to the blood, and the liver converts amino acid carbons to glucose or ketone  A 9-month-old boy was admitted to the hospital for evaluation of chronic vomiting and developmental delay. Lab studies revealed elevated Knowledge levels of NH3, Gln, Ala, and ornithine. Check - Flash Citrulline was low. Card-2 Which Urea Cycle enzyme is deficient in the patient? References 1. Lieberman M.A., Ricer R (2014) BRS: Biochemistry, Molecular Biology, and Genetics, 6th Inspire Edition. Empower Williams & Lippincott Elevate a Wilkins, Wolters Kluwer business. 2. Harvey, R. A. & Ferrier, D. R. (2014). Lippincott’s Illustrated Reviews: Biochemistry, 6th Edition. New York: Wolters Kluwer | Lippincott Williams & Wilkins. 3. Ferrier D.R., Jameson B.A (2015) Lippincott Illustrated Reviews Flash Cards BIOCHEMISTRY. Wolters Kluwer Health  Thank you. For more information please contact: Dr Moe Thida Kyaw Lecturer Human Biology Department [email protected] IMU Education Sdn Bhd No. 126, Jalan Jalil Perkasa 19 199201005893 (237397-W) Bukit Jalil, 57000 Kuala Lumpur, Malaysia 603 8656 7228 Insert footnotes here (if any). imu.edu.my Formerly known as International Medical University.