CLICHM1 Proteins

• Proteins


  Chief nitrogenous macromolecules of cellular structure and organization (50-70% of cell's dry weight)
• Proteins


  • Consist of a definitive number of amino acids arranged in a specific sequence
  • Amphoteric: Can be positive or negatively charged
  • Macromolecules: Because of its structure, a polypeptide/polymer
  • Because of its weight: Approximately 120 kDa
  • Serum proteins: 66-700 kDa
• Nitrogen Balance


  1. Anabolism: Build-up of proteins or protein synthesis through the Central Dogma

  2. Catabolism: Protein breakdown
• Positive Nitrogen Balance


  More nitrogen is incorporated in the body than what is being excreted
• Positive Nitrogen Balance

  • During pregnancy, growing children, recovering from illness
• Negative Nitrogen Balance


  More nitrogen is excreted than what is being incorporated
• Negative Nitrogen Balance


  • Burns, wasting diseases, starvation (ketones), muscular dystrophy, continuous fever
• Liver


  Responsible for the synthesis of majority of serum proteins except immunoglobulins (by plasma cells)
• Converting Intracellular Proteins to Free Amino Acids

  1. Lysosomal Pathway: Degradation of extracellular proteins

  2. Cytosolic Pathway: Degrades important intracellular proteins
• Transamination or Deamination


  Removes amino acids
• Zwitter Ion


  Type of amino acid with 2 different charges with a net charge of 0
• Isoelectric Point (pI)


  pH value of which the sum of the molecules charge is equal to zero
• pH > pI


  Protein is negatively charged
• pH < pI


  Protein is positively charged
• Denaturation of Proteins


  Loss of functional characteristics. 2nd, 3rd, and 4th structures are damaged
• Causes of Protein Denaturation

  • Heat, trauma (mechanical), exposure to radiation, chemicals
• Functions of Proteins


  • Repair body tissues (collagen)
  • Important in blood coagulation and immunologic function
  • Transport of metabolic substances (albumin, ferritin, ceruloplasmin)
  • Maintenance of osmotic/oncotic pressure (albumin)
  • Maintenance of blood pH as buffer (hemoglobin)
  • Biocatalysts (Enzymes)
• Primary Structure/Linear Sequence


  Sequence of amino acids in the polypeptide chain. Determines the overall shape of the protein.
• Secondary Structure


  Arises from the interaction among the different segments of a polypeptide chain. Incorporation of hydrogen bonds to add flexibility, strength, and stability.
• Types of Secondary Structure

  • Alpha-helix: Chain forms a regular helix; coil resembling a spring
  • Beta-pleated Sheets: In fully extended structure; flat, corrugated structures
  • Random Coils: No apparent pattern
• Tertiary Structure


  Actual 3-dimensional structure or folding pattern of the protein. Maintained by covalent disulfide bond. Responsible for many physical and chemical functions.
• Quaternary Structure


  Association of several polypeptide chains into larger "oligomeric" aggregate unit.
• Quaternary Structure


  • Hgb, LDH, CPK
• Classification of Proteins


  • Simple: Contain peptide chains that on hydrolysis yield only amino acids
  • Globular: Relatively symmetrical with compactly folded and coiled polypeptide chains
  • Fibrous: More elongated and asymmetrical and have a higher viscosity
  • Conjugated: Protein (apoprotein) + nonprotein (prosthetic group)
• Globular Proteins

  • Hgb, Immunoglobulins, Enzymes, peptide hormones
• Fibrous Proteins


  • Fibrinogen, troponin, collagen
• Pre-Albumin (Transthyretin)


  Aka Transthyretin (Trans – transporter, Thy – thyroid hormones, Retin – retinol). It migrates before albumin in the classic electrophoresis of serum or plasma proteins. Binds with retinol-binding protein to form a complex that transports retinol (vit A). Rich in tryptophan and contain 0.5% carbohydrate. Indicator of poor nutrition status. Used to confirm if an unknown sample is CSF. A transporter protein for thyroid hormones such as Triiodothyronine and Thyroxine.
• Retinol


  Vitamin A needed for normal vision, immune system, for reproduction, growth, and development. Promotes proliferation (incorporated in skin care products)
• Clinical Significance of Pre-Albumin

  • Increased in/during: Alcoholism, Chronic renal failure, and Steroid treatment
  • Decreased in/during: Poor nutrition (Sensitive marker; When a diet is deficient in protein, hepatic synthesis of protein is also reduced), Liver disorder (hepatic damage), Malignancy, Tissue necrosis
• Albumin


  Largest protein fraction (52-62% of all the serum proteins). Synthesized in the liver at a rate that is dependent on protein intake. Indicator of nutritional status. Allows clinician to interpret high or low calcium and magnesium levels. Albumin binds about ½ to each of those ions. More informative regarding: Nutritional status, Liver synthetic capacity, and Enteropathy. Used to calculate the fraction of globulin. (TP – Albumin = Globulin)
• Albumin as a Major Regulator of Osmotic Pressure

  Responsible for nearly 80% of colloid osmotic pressure (COP). COP: maintains the appropriate fluid balance in the tissue. Decrease in albumin levels also results in loss of water from blood and its entry into interstitial fluid causing Edema.
• Albumin as a Negative Acute Phase Reactant

  It decreases acute inflammatory response. Serves as inhibitors/mediators of inflammatory processes. Known to be elevated rapidly in cases of inflammation, however in albumin, its concentration will decrease.
• Clinical Significance of Hyperalbuminemia

  • No clinical significance. However, increased albumin can be seen in cases of: Hemoconcentration, Dehydration, Excessive albumin infusion (related to blood banking)
• Clinical Significance of Hypoalbuminemia

  • Impaired synthesis: Primary Hypoalbuminemia: Liver disease, Secondary Hypoalbuminemia: Diminished protein intake, Malabsorption or malnutrition. Kwashiorkor: Disease state wherein the diet is severely deficient of protein (high content of starch food). Decreased serum albumin, Immune deficiency, Edema, Ascites (large abdomen). Marasmus: Protein and energy sources are deficient. Protein calorie starvation which leads to general wasting of muscles and subcutaneous tissues. Lesser edema. Nephrotic syndrome (renal loss): Disease state where you can see the lowest plasma albumin levels. Sudden decrease is indicative of nephrosis. Gradual decrease is indicative of cirrhosis. Increased catabolism due to tissue damage and inflammation. Example is severe burns.
• Globulins


  Consists of alpha1, alpha2, beta, gamma fractions. Normal A/G Ratio: 1.3-3:1 (For every 1.3-3 albumin concentration, there must be 1 globulin).
• Conditions with Low A/G Ratio

  • Liver diseases, Infectious diseases, Multiple myeloma, Nephritis
• Globulin


  Conc Total protein – conc Albumin
• Alpha-1-antitrypsin


  Most abundant protein in the Alpha1-globulins (90%). Function: Inhibits protease neutrophil elastase. Enzyme released by WBC to combat infection. Disadvantage: The action of this enzyme can cause destruction of alveoli, leading to emphysema.
• Conditions with Increased Alpha-1-antitrypsin


  • Inflammation, Pregnancy, Contraceptive use
• Conditions with Decreased Alpha-1-antitrypsin

  • Emphysematous pulmonary disease, Juvenile hepatic cirrhosis