BIOCHEMISTRY MIDTERM REVIEWER

Protein Structure and Function

CORE CONCEPTS

Amino Acids: Building Blocks of Proteins

●​ Composed of:
○​ Central carbon (C)
○​ Amino group (-NH₂)
○​ Carboxyl group (-COOH)
○​ Hydrogen atom (H)
○​ Variable side chain (R group)
●​ Only 20 common amino acids are used in protein synthesis.
●​ Differ based on their R group.

Essential vs Non-Essential Amino Acids

●​ Essential: Cannot be synthesized by the body; must be obtained from diet

○​ Mnemonic: MATTVILLPHLY
○​ Includes: Methionine, Arginine, Tryptophan, Threonine, Valine,
Isoleucine, Leucine, Phenylalanine, Histidine, Lysine
●​ Non-Essential: Synthesized by the body
○​ Includes: Alanine, Glycine, Serine, Tyrosine, Glutamate, Glutamine,
Aspartate, Asparagine, Cysteine, Proline

Amino Acid Linkage

●​ Linked by peptide bonds via dehydration synthesis.

●​ Chains of amino acids = polypeptides
●​ Polypeptides = protein
PROTEIN STRUCTURE

1. Primary Structure

●​ Linear sequence of amino acids

●​ Determined by DNA triplet codes
●​ Example: Insulin has two chains (A and B)

2. Secondary Structure

●​ Local folding: α-helix and β-pleated sheet

●​ Stabilized by hydrogen bonds

3. Tertiary Structure

●​ 3D shape of a polypeptide
●​ Interactions between R groups
●​ Includes disulfide bonds, ionic bonds, hydrophobic interactions

4. Quaternary Structure

●​ Multiple polypeptide chains (subunits)

●​ Example: Hemoglobin (4 subunits), DNA polymerase (10 subunits)

PROTEIN FUNCTIONS

Function Example/Role

Movement Actin & Myosin in muscle contraction

Structure Collagen (connective tissues), Keratin (hair, nails, feathers)

Biochemical Control Enzymes (e.g., amylase, lipase, pepsin)

Transport Hemoglobin transports oxygen

Storage Casein in milk stores amino acids for infants

Regulation Insulin regulates blood glucose

Defense Immunoglobulins (IgG, IgA, IgM, IgD, IgE) fight pathogens

ENZYMES

●​ Biological catalysts that lower activation energy

●​ Specific to substrates via active sites
●​ Affected by:
○​ Temperature
○​ pH
○​ Substrate concentration
●​ Clinical relevance: Enzyme deficiencies can cause diseases

IMMUNOGLOBULINS (Antibodies)

Type Structure Function

IgG Monomer Crosses placenta, secondary immune response

IgA Dimer Found in secretions, protects mucosal surfaces

IgM Pentamer Primary immune response, restricted to bloodstream

IgD Monomer Surface of B cells, antigen receptor

IgE Monomer Allergic responses, parasite defense

PROTEIN SHAPE & DENATURATION

●​ Shape determines function

●​ Denaturation: Loss of structure due to heat, pH, chemicals
●​ Renaturation: Possible if conditions are restored

GENETIC LINK: DNA & PROTEINS

●​ DNA triplet codes determine amino acid sequence

●​ Mutation example: Sickle Cell Anemia
○​ Glutamic acid → Valine substitution
○​ Causes hemoglobin to form fibers → sickle-shaped RBCs
 ○​ Leads to impaired blood flow and complications

Protein Metabolism Overview

●​ Purpose: Synthesis, breakdown, and utilization of proteins and amino acids

●​ Two major processes:
○​ Anabolism: Protein synthesis
○​ Catabolism: Protein breakdown

Protein Synthesis (Anabolism)

●​ Steps:
○​ Gene transcription (DNA → mRNA)
○​ Translation (mRNA → protein at ribosome)
○​ Post-translational modifications
●​ Essential proteins:
○​ Albumin: Maintains fluid balance and transports substances

Protein Catabolism

●​ Process:
○​ Proteins broken down by proteolytic enzymes
○​ Amino acids released
○​ Excess nitrogen → converted to urea (via urea cycle)
○​ Carbon skeletons → energy or glucose (gluconeogenesis)

Urea Cycle

●​ Purpose: Detoxify ammonia by converting it to urea

●​ Location: Liver (mitochondria and cytosol)
●​ Steps:
 1.​ Ammonia + CO₂ → Carbamoyl phosphate (via CPS1)
2.​ Carbamoyl phosphate + Ornithine → Citrulline (via OTC)
3.​ Citrulline + Aspartate → Argininosuccinate (via ASS)
4.​ Argininosuccinate → Arginine + Fumarate (via ASL)
5.​ Arginine → Urea + Ornithine (via Arginase)
●​ Clinical relevance: Prevents ammonia toxicity

Urea Cycle Disorders

●​ Symptoms by severity:
○​ Mild: Vomiting, lethargy
○​ Moderate: Confusion, behavioral changes
○​ Severe: Seizures, cerebral edema
○​ Life-threatening: Coma, organ failure
○​ Chronic: Developmental delays
○​ Late sequelae: Motor dysfunction, epilepsy

Diagnostic Laboratory Tests

Test Normal Range High Levels Low Levels

Plasma Ammonia Adults: 10–50 Brain damage risk Sampling error

µmol/L

Plasma Glutamine 500–850 µmol/L Metabolic stress Rare

Plasma Citrulline 10–45 µmol/L Citrullinemia Early cycle defect

Urinary Orotic Acid <10 mmol/mol Carbamoyl phosphate Rare

creatinine excess

Blood Urea 8–20 mg/dL Kidney issues Liver/

Nitrogen UCD

Liver Function Tests ALT: 7–56 U/L, Liver damage Rare

AST: 10–40 U/L
Enzyme Structure and Function

●​ Definition: Biological catalysts made of proteins

●​ Function: Speed up reactions by lowering activation energy
●​ Structure:
○​ Made of amino acids
○​ Folded into specific shapes
○​ May include cofactors
●​ Damage causes: Heat, disease, chemicals

Types of Enzymes

1.​ Oxidoreductases: Redox reactions (e.g., dehydrogenases)

2.​ Transferases: Transfer functional groups
3.​ Hydrolases: Hydrolysis reactions (e.g., digestive enzymes)
4.​ Lyases: Add/remove groups to form/break double bonds
5.​ Isomerases: Rearrange functional groups within molecules
6.​ Ligases: Form bonds by removing water (ATP involved)

Functional Groups in Biomolecules

Group Properties Example

Hydroxyl (-OH) Polar, hydrophilic Alcohols

Carboxyl (-COOH) Acidic, releases H⁺ Amino acids

Amino (-NH₂) Basic, accepts H⁺ Proteins

Phosphate (-PO₄) Acidic, releases H⁺ DNA/RNA

Sulfhydryl (-SH) Polar Cysteine

Methyl (-CH₃) Nonpolar Lipids

Enzyme Mechanisms

●​ Lock and Key Model: Substrate fits perfectly

●​ Induced Fit Model: Enzyme changes shape to fit substrate
●​ Steps:
1.​ Substrate binds to active site
2.​ Reaction occurs
3.​ Product released

Digestive Enzymes

Enzyme Source Function

Amylase Salivary glands, pancreas Breaks starch into sugars

Protease Stomach, pancreas Breaks proteins into amino acids

Lipase Pancreas, small intestine Breaks fats into glycerol & fatty acids

Factors Affecting Enzyme Activity

●​ Concentration: More substrate = faster reaction (until saturation)

●​ Temperature: Optimal at body temp; too high = denaturation
●​ pH: Narrow optimal range; extremes = denaturation
●​ Inhibitors: Block active sites, slow reactions

Enzyme Deficiency Diseases

1.​ G6PD Deficiency: Hemolytic anemia, common worldwide

2.​ Congenital Adrenal Hyperplasia: Cortisol deficiency, hormone imbalance
3.​ Gaucher’s Disease: Glucocerebroside buildup in organs
4.​ Pyruvate Kinase Deficiency: Red blood cell breakdown, anemia
Genetic Variants and Disease

●​ Topics Covered:
○​ Mechanisms linking genetic variants to disease
○​ Types of disease associations
○​ Methods to identify variant-disease associations
○​ Clinical applications (e.g., PKU, Tay-Sachs)
●​ Activities:
○​ Literature review and case discussion
○​ Group brainstorming and case reporting

Origins of Life and Chemical Evolution

From Inorganic to Organic Matter

●​ Life began from inorganic molecules transformed into organic compounds.

●​ Model of the Atom: Protons, neutrons, electrons in shells around a nucleus.

Timeline of the Universe

●​ Big Bang → Formation of atoms → Galaxies → Solar system → Life on Earth

●​ Stars created heavier elements via nuclear fusion and supernovae.

Miller-Urey Experiment

●​ Simulated early Earth conditions.

●​ Combined gases (CH₄, NH₃, H₂O, H₂) with electric sparks.
●​ Produced amino acids → evidence for chemical evolution.

Bubble Hypothesis (Louis Lerman, 1992)

●​ Volcanic gases trapped in sea bubbles → organic molecules formed.

●​ Bubbles burst → molecules exposed to UV/lightning → complex molecules.
●​ Rain returned molecules to ocean → cycle repeated.
Nucleic Acids: DNA & RNA

Nucleotide Structure

●​ Composed of:
○​ Phosphate group
○​ Pentose sugar (ribose or deoxyribose)
○​ Nitrogenous base (Purines: A, G; Pyrimidines: C, T/U)

DNA vs RNA Comparison

Feature DNA RNA

Sugar Deoxyribose Ribose

Strands Double-stranded Single-stranded

Bases A, T, C, G A, U, C, G

Function Genetic blueprint Protein synthesis, regulation

Location Nucleus, mitochondria Nucleus, cytoplasm, ribosomes

Stability More stable Less stable

Central Dogma of Molecular Biology

Transcription & Translation

●​ DNA → mRNA (Transcription) in nucleus

●​ mRNA → Protein (Translation) in ribosome
●​ tRNA brings amino acids
●​ rRNA part of ribosome
●​ Regulatory RNAs (e.g., microRNA) control gene expression

Genetic Inheritance & Disorders

Punnett Squares

●​ Used to predict genetic outcomes.

●​ Example: Sickle Cell Anemia (Ss × Ss → 25% ss, 50% Ss, 25% SS)
Types of Inheritance

Type Pattern Examples

Autosomal Dominant One altered gene Huntington’s, Marfan Syndrome

Autosomal Recessive Two altered genes PKU, Cystic Fibrosis

X-linked Dominant One X gene Rett Syndrome

X-linked Recessive One X gene (males affected) Hemophilia A, DMD

Mitochondrial Maternal inheritance LHON

Chromosomal Abnormal chromosomes Down Syndrome, Turner

Syndrome

Multifactorial Genes + environment Diabetes, Hypertension, Cleft Lip

DNA Types: Nuclear vs Mitochondrial

Feature Nuclear DNA Mitochondrial DNA

Location Nucleus Mitochondria

Structure Linear Circular

Size ~3 billion bp ~16,569 bp

Genes ~20,000–25,000 37

Inheritance Both parents Mother only

Mutation Rate Lower Higher

Repair Robust Limited

Function Cell function & heredity Energy production

Chromosome Abnormalities

●​ Numerical: Trisomy (extra), Monosomy (missing)

●​ Structural: Deletion, Duplication, Inversion, Translocation
 ●​ Pedigree vs Genogram

Chart Focus Use

Pedigree Genetic inheritance Genetic counseling

Genogram Psychosocial + medical Holistic family assessment

Role of Nurses in Genetics

●​ Education & Counseling: Explain inheritance and risks

●​ Family History: Construct pedigrees/genograms
●​ Testing Support: Guide patients through genetic testing
●​ Disease Management: Tailor care plans
●​ Health Promotion: Advocate lifestyle changes
●​ Collaboration: Work with geneticists and counselors