Biochemistry: Amino Acids, Proteins, and pH Lecture Notes

Biochemistry Study Guide: Amino Acids

  • Definition and Function:

    • Amino acids are the smallest units and fundamental building blocks of proteins.
    • Without amino acids, the body cannot produce vital components including:
      • Enzymes
      • Antibodies
      • Muscles
      • Hormones
      • Albumin
      • Hemoglobin
    • Dietary sources include eggs, meat, milk, fish, and soy.

  • Amino Acid Classification:

    1. Essential Amino Acids:
      • Definition: The body cannot synthesize these; they must be obtained entirely through food.
      • There are nine essential amino acids that must be memorized:
        1. Histidine
        2. Isoleucine
        3. Leucine
        4. Lysine
        5. Methionine
        6. Phenylalanine
        7. Threonine
        8. Tryptophan
        9. Valine
    2. Nonessential Amino Acids:
      • Definition: The body has the capacity to manufacture these internally.
      • Examples include:
        • Asparagine
        • Glutamate
        • Alanine
        • Serine
        • Aspartate
    3. Conditionally Essential Amino Acids:
      • Definition: These are normally synthesized by the body but become essential (must be supplemented via diet) during periods of physiological stress or rapid development.
      • Circumstances requiring intake: Burns, trauma, severe illness, or rapid growth.
      • Examples include:
        • Arginine
        • Tyrosine
        • Glutamine
        • Cysteine
        • Glycine
        • Proline

  • Basic Chemical Structure:

    • Every amino acid contains three critical components attached to a central carbon:
      1. Amino group: $H_2N$
      2. Carboxyl group: $COOH$
      3. Side chain (R group): This specific group determines the individual identity and properties of each amino acid.

  • Board Exam Insight (Phenylketonuria):

    • Metabolic pathway: $Phenylalanine$ is typically converted into $Tyrosine$.
    • Clinical application: If a patient has PKU (Phenylketonuria) and cannot metabolize phenylalanine, $Tyrosine$ becomes an essential amino acid for that individual.

Protein Structure and Function

  • General Roles of Proteins:

    • Transport: Moving substances (e.g., Albumin, Hemoglobin).
    • Immune Defense: Fighting infection (e.g., Antibodies/Immunoglobulins).
    • Catalysis: Accelerating chemical reactions (e.g., Enzymes).
    • Regulation: Carrying signals (e.g., Hormones like Insulin).
    • Movement: Facilitating muscle contraction (e.g., Actin and Myosin).

  • Levels of Protein Structure:

    • Primary Structure: The specific sequence of amino acids in a chain.
    • Secondary Structure: Local folding patterns, specifically the $\alpha$-helix and $\beta$-sheet.
    • Tertiary Structure: The overall three-dimensional folding of the protein, which determines its specific job or function.
    • Quaternary Structure: The complex formed when multiple protein chains (subunits) join together. A classic example is $Hemoglobin$.

  • Plasma Proteins:

    • Prealbumin:
      • Functions as a transporter for $T_3$ and $T_4$ (thyroid hormones).
      • Serves as a clinical marker for nutritional status.
      • Decreased levels: Seen in poor nutrition and inflammation.
    • Albumin:
      • The most abundant plasma protein.
      • Primary jobs: Maintains oncotic pressure and serves as a carrier for drugs, hormones, and calcium.
      • Low Albumin (Hypoalbuminemia) causes: Liver disease (decreased synthesis), kidney disease (loss through urine), and malnutrition.
      • High Albumin: Usually indicates dehydration.
    • Globulins (Classified by Electrophoresis):
      • $\alpha_1$ (Alpha-1): $Alpha-1\text{ antitrypsin}$ (Protects lungs by stopping neutrophil elastase; deficiency leads to early emphysema/COPD).
      • $\alpha_2$ (Alpha-2): $Haptoglobin$ (Binds free hemoglobin; levels decrease during intravascular hemolysis).
      • $\beta$ (Beta): $Transferrin$ (The "Iron Taxi" or iron transporter).
      • $\gamma$ (Gamma): $Immunoglobulins$ (Antibodies; levels increase during infection or in conditions like multiple myeloma; decrease in immunodeficiency).

  • Serum Protein Electrophoresis (SPEP):

    • Purpose: To separate proteins based on charge and size.
    • Migration Order: Albumin $\rightarrow$ $\alpha_1$ $\rightarrow$ $\alpha_2$ $\rightarrow$ $\beta$ $\rightarrow$ $\gamma$.

  • Total Protein Reference Range:

    • Normal: $6.5-8.3\,g/dL$.
    • Hyperproteinemia: Elevated total protein, typically caused by dehydration.
    • Hypoproteinemia: Decreased total protein, caused by liver disease, kidney disease, or malnutrition.

Trace Elements and Mineral Metabolism

  • General Concept: Micronutrients that act as essential helpers for enzymes; without them, proteins cannot function correctly.

  • Zinc ($Zn$):

    • Functions: Essential for the immune system, $DNA$ synthesis, and wound healing.
    • Deficiency symptoms: Poor wound healing, hair loss, and immune dysfunction.

  • Copper ($Cu$):

    • Functions: Involved in iron metabolism, the nervous system, and collagen formation.
    • Clinical considerations: Associated with Wilson disease (overload) and Menkes disease (deficiency).

  • Selenium ($Se$):

    • Function: Acts as an antioxidant to protect cells.
    • Deficiency: Associated with cardiomyopathy and hypothyroidism.
    • Toxicity symptom: "Garlic breath" and hair loss.

  • Magnesium ($Mg$):

    • Importance: Crucial for heart rhythm, muscle function, and $PTH$ (Parathyroid Hormone) regulation.
    • Low levels: Lead to arrhythmias (such as Torsades de pointes) and hypocalcemia.
    • High levels: Seen in renal failure; causes muscle weakness.

  • Chromium ($Cr$):

    • Function: Potentiates the action of insulin.
    • Deficiency: Results in poor glucose tolerance and neuropathy.

  • Iron ($Fe$) and Diagnostic Panels:

    • Main Job: Formation of hemoglobin for oxygen transport.
    • Iron Deficiency Profile:
      • $Iron \downarrow$
      • $Ferritin \downarrow$
      • $Transferrin \uparrow$
      • $TIBC \text{ (Total Iron Binding Capacity) } \uparrow$
    • Iron Overload Profile:
      • $Iron \uparrow$
      • $Ferritin \uparrow$
      • $TIBC \downarrow$
    • Anemia of Chronic Disease Profile:
      • $Iron \downarrow$
      • $Transferrin \downarrow$
      • $Ferritin \uparrow$

  • Toxic Elements:

    • Lead ($Pb$): Causes anemia, kidney damage, and neurotoxicity (memory loss).
    • Board Pearl (Lead): Examination of blood smears reveals "Basophilic stippling."
    • Mercury ($Hg$): Causes neurotoxicity and kidney damage.

pH, Acids, and Bases

  • Biochemical Definitions:

    • Acid: A substance that releases Hydrogen ions ($H^+$). Example: Carbonic acid.
    • Base: A substance that accepts $H^+$ ions. Example: Bicarbonate.
    • Acidemia: $pH$ falls below normal.
    • Alkalemia: $pH$ rises above normal.

  • Reference Ranges for Arterial Blood Gases (ABGs):

    • $pH: 7.35-7.45$ (Overall acid-base balance)
    • $PCO_2: 35-45\,mmHg$ (Lungs/Ventilation status)
    • $HCO_3: 22-26\,mmol/L$ (Kidneys/Metabolic status)
    • $PO_2: 80-100\,mmHg$ (Oxygenation status)

  • The Bicarbonate Buffer System:

    • This is the body's most important buffer system for maintaining $pH$ stability.
    • Reaction: $CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$
    • Relationships:
      • $\uparrow CO_2 \rightarrow \uparrow \text{Acid} \rightarrow \downarrow pH$ (Acidic side)
      • $\downarrow CO_2 \rightarrow \uparrow \text{Base} \rightarrow \uparrow pH$ (Alkaline side)

Acid-Base Disorders and Interpretation

  • Four Primary Disorders:

    1. Respiratory Acidosis:
      • Cause: The lungs retain $CO_2$ (e.g., COPD).
      • Pattern: $pH \downarrow$ and $CO_2 \uparrow$
    2. Respiratory Alkalosis:
      • Cause: Hyperventilation (breathing too much), leading to excessive $CO_2$ loss.
      • Pattern: $pH \uparrow$ and $CO_2 \downarrow$
    3. Metabolic Acidosis:
      • Cause: Kidney dysfunction or excess metabolic acid production.
      • Pattern: $pH \downarrow$ and $HCO_3 \downarrow$
    4. Metabolic Alkalosis:
      • Cause: Excess bicarbonate or loss of acid (e.g., severe vomiting).
      • Pattern: $pH \uparrow$ and $HCO_3 \uparrow$

  • Buffer Systems (Shock Absorbers):

    • Buffers prevent sudden shifts in $pH$.
    • Bicarbonate Buffer: Located in the blood.
    • Phosphate Buffer: Located in cells and the kidneys.
    • Protein/Hemoglobin Buffer: Located in the blood.

  • ABG Interpretation Steps:

    1. Analyze $pH$: Determine if it indicates Acidosis ($< 7.35$) or Alkalosis ($> 7.45$).
    2. Analyze $CO_2$: If it moves in the opposite direction of $pH$ (e.g., $pH \downarrow$ while $CO_2 \uparrow$), the disorder is Respiratory.
    3. Analyze $HCO_3$: If it moves in the same direction as $pH$ (e.g., $pH \downarrow$ and $HCO_3 \downarrow$), the disorder is Metabolic.
    4. Finalize: Decide the primary disorder and check for evidence of compensation.

  • Regulation Organs:

    • Lungs: Control $CO_2$ levels; respond rapidly.
    • Kidneys: Control $HCO_3$ levels; respond slowly.