Proteins PDF

Preview

Summary

Introduction to Proteins...

Description

I. PROTEINS PROTEINS – Greek word “proteios” meaning first rank of importance    

considered as the most versatile molecules in our bodies provide 12 to 20% of the total daily body energy requirement composes 50 to 70% of the cell’s dry weight composed of polymers of covalently-linked amino acids

AMINO ACIDS – fundamental building blocks of the proteins  

 



considered as a macromolecule STRUCTURE – varies depending on the radical group (R) or side chain o Amino group (left) o Carboxyl group (right) o Altocarbon (carbon in the middle) – center of structure o Hydrogen (below) Electric charge depends on pH of the solution and type of R group is a Zwitterion - a molecule which possess both a positive and negative charge o net charge is zero o because of its carboxyl and amino group o in basic solution – amino acid is negatively charged  dissociation of the proton from the carboxyl group (COOH)  Hydrogen (positively charged) dissociates to the carboxyl group o in acidic solution – amino acid is positively charged  NH2 (part of the amino acid) accepts proton (hydrogen) = NH3+ o These charges affect how each protein moves in an electric field – allows us to separate proteins  Electrophoresis – migration of a charged particle to an electric field have Isoelectric Point – the sum of molecule’s charges is zero

Protein Structure - determines the shape of a given protein molecule and affect the function of that protein 

Peptide Bond (Amide Linkage) - link which bridges amino acids to form the protein or a peptide o formed between two amino acids specifically between their amino group and the carboxyl group with water as a by product

TYPES OF AMINO ACIDS 1. Glucogenic AA – generates the precursors of glucose such as pyruvate

2. Ketogenic AA – degraded to acetyl CoA which also serves as a source of energy in the process of gluconeogenesis Primary Structure –composed of the linear sequence of amino acids   

simplest determine the overall shape of the protein on how it bends, folds and twist (flat or coils) Example: Insulin

Secondary Structure – coiling and folding of the protein chain; how the protein chain twists and bends along its length  

Alpha helix – helical structure; coil and resembles a spring Beta pleated sheet – flat, corrugated structure

Tertiary Structure – have three-dimensional shape  

Globular – oval or circular in shape Fibrous - cylindrical (ex. muscle fibers)

Quarternary Structure – When two or more polypeptide chains associate closely together to make-up multichain complex  

most complex, combination of sub-units Example: Heme – combination of the 4 heme groups

CLASSIFICATION OF PROTEINS ACCORDING TO FUNCTION: 1. Enzymes – made up of protein that serves as biochemical catalyst (speeds up chemical reaction) 2. Structural Proteins –usually long, fibrous molecules o Collagen – found primarily in the bone; skin, tendons, ligaments o Keratin- found in hair and nails 3. Contractile Proteins – important for producing movement o involved in the contraction and relaxation of muscles o usually long, fibrous materials 4. Antibodies (immunoglobulins) – neutralize foreign materials or microbes that invade our system o IgA o IgM o IgG o IgE o IgD

5. Transport proteins - serve a vital function in carrying materials from one part of the body to another through circulation o Hemoglobin - circulation o Myoglobin – tissue Peptide Hormones – hormones made up of proteins which function is to regulate metabolism  

usually has the suffix -ine Examples: Epinephrine (Adrenaline), Norepinephrine

SPECIFIC PLASMA PROTEINS I.

Major Components - These are protein components that are readily detectable by electrophoresis (way of separating proteins from blood) and stained by conventional clinical laboratory techniques (example: methyl orange, bromocresol green) Serum Protein Electrophoresis (SPE)   

Anode - positive pole found at the left side o negatively charged particles will migrate towards the anode Cathode – negative pole found at the right side o positively charged particles will migrate towards the cathode Albumin – fraction of the serum protein that is most anodal – nearest to the anode

1. Prealbumin  It is the fraction that migrates in a position faster than albumin toward the anode.  It has a tetrameric structure and each monomer can bind a molecule of thyroxine (thyroxine transporter)  It is also called thyroxine-binding prealbumin (TBPA) or transthyretin (TTR).  It also binds with the retinal-binding protein (RBP) which complexes with Vitamin A to transport it to the body (especially to the eyes)  It has a short half-life in the circulation (barely 2 days) compared with other major serum proteins. Its rate is sensitive to intake of adequate nutrition and to alteration in hepatic function where it is produced.  It is a good indicator for nutritional status of the body.  It crosses more easily into the CSF than other serum proteins.  Decreased: poor nutrition  Increased: alcoholism, chronic renal failure  Normal Value: 18-45 mg/dL

2. Albumin – most anodal, most abundant and responsible for half of the plasma protein mass  It serves as a mobile repository of amino acids for incorporation into other proteins.  It is the general transport protein or carrier (transports bilirubin)  Its half-life in the circulation is 17 days  Decreased: edema (pamamanas)  Increased of serum albumin concentration: dehydration, prolonged application of tourniquet during venipuncture  Determination of Ca and Mg is very dependent on albumin – electrolytes are bound  Dye Binding methods for albumin measurements employ o Bromocresol Green (BCG) o Hydroxyozobenzene Benzoic Acid (HABA)  The presence of albumin in the urine indicates abnormality in the kidney (because albumin is considered as a macromolecule  Normal Value: 3.5 to 5 mg/dL  The bonds to the serum protein electrophoresis from the anode to the cathode o Then globulins (-1 globulin, -2 globulin, β globulin, gamma globulin) 3. 1-Antitrypsin (AAT)  Major component of the 1-globulins  It has the capacity to combine with trypsin and inactivate it o Trypsin – responsible for destruction of tissue  It is one of the serum glycoproteins that rise in response to acute inflammation o Acute Phase Reactant – its concentration will increase during inflammation  Normal Value: 145 – 270 mg/dL 4. -2 macroglobulin  migrate from the 2 of the SPE  largest major nonimmunoglobulin protein in plasma  Higher at women – estrogen  Indicator of nephrotic syndrome o concentration increases up to 10x the normal value  Normal Value: 150 – 420 mg/dL 5. β-2 microglobulin  Migrates to β2 region of the SPE  Light chain component of the major histocompatibility complex (HLA-Human Lymphocyte Antigen)  Increased in inflammatory diseases o Rheumatoid Arthritis



o Systemic Lupus Erythematosus (SLE) Normal Value: 0.2 – 2.8 ug/dL

6. Haptoglobin  Migrates in the 2 region  It combines with hemoglobin (especially -chain) released by lysed red cells in order to preserve body iron and protein stores.  Its half-life in the circulation is 4 days  Increased in response to stress, infection, acute inflammataion or tissue necrosis  Used to evaluate degree of intravascular hemolysis – hemolytic transfusion reaction (incompatible blood) and HDN (hemolytic disease of the newborn) – decreased  Normal Value: 26 – 185 mg/dL 7. Transferrin – siderophilin  It is a major β-globulin component  It transports ferric ions to the storage sites – liver, bone marrow, reticuloendothelial system  Increased in pregnant women  Negative Acute Phase Reactant – concentration decreases during inflammation  Normal Values: 215-365 mg/dL (males); 250-380 mg/dL (females) 8. Fibrinogen  It is the most abundant to the coagulation factors  It forms the fibrin clot – essential to stop bleeding  Increased with other acute phase reactants, pregnancy, use of contraceptive medications  Positive Acute Phase Reactant – concentration increases during inflammation  Normal Values: 200-400 mg/dL  used to differentiate plasma and serum o Absent in serum – converted into fibrin o Present in plasma II.

MINOR COMPONENTS 1. Ceruloplasmin – copper-binding protein  Enzyme responsible for oxidizing iron from ferrous to ferric state  Increased at individuals under oral contraceptive therapy, pregnancy  Disordered copper metabolism results to Wilson's disease due to ceruloplasmin deficiency.

o Wilson’s Disease – characterized by deposition of copper into different body tissues (skin, liver, brain, cornea of the eye)  Normal Value: 18-45 mg/dL 2. Hemoplexin  It migrates to the β-region of the SPE  It binds heme released by degradation of haemoglobin  Most profoundly decreased in intravascular hemolysis  There must be no free hemoglobin to the plasma – free hemoglobin indicates intravascular hemolysis  Normal Value: 50-115 mg/dL 3. 1-Acid Glycoprotein – orosomucoid  It has high affinity to progesterone and can be important in its transport or metabolism  Increased during pregnancy, cancer, rheumatoid arthritis  Normal Value: 55-140 mg/dL 4. C-Reactive Protein (CRP)  Earliest indication of inflammation – highly sensitive acute phase reactant  It is used to differentiate infections caused by bacteria or virus o High during bacterial infections o Low CRP level during viral infections  Persons with high normal CRP concentrations are at greater risk for stroke or myocardial infarction than those with low normal values  Normal Value:...