Med 1001: Molecular Basis of Cell - Biochemistry

Detailed Explanations for First-Year MBBS Students

LECTURE 1 - Water, Acids, Bases, and pH

Why does this matter in medicine?

1. Water - The Universal Solvent

• The oxygen atom pulls electrons strongly toward itself (it is electronegative), so the two hydrogen atoms carry a slight positive charge (δ+) and the oxygen carries a slight negative charge (δ-).
• This makes water a dipolar (polar) molecule - it has two poles of charge.
• Because of this polarity, water molecules attract each other through hydrogen bonds - the slightly positive hydrogen of one water molecule is attracted to the slightly negative oxygen of another.

• Polar substances (like glucose, Na⁺, K⁺, ATP, proteins) dissolve in water because water molecules surround them - this is called hydration.
• The Na⁺ (positive) is surrounded by the negative ends (oxygen) of water molecules. K⁺ similarly. Cl⁻ (negative) is surrounded by the positive ends (hydrogen). These surrounding layers are called hydration shells.
• Non-polar substances (like fats, oils) do NOT dissolve in water - this is the basis of the cell membrane's lipid bilayer.

• A single hydrogen bond is only ~4 kcal strong (about 1/20th the strength of a covalent bond).
• Each bond lasts only about 10 picoseconds (10 × 10⁻¹² seconds) - they break and re-form constantly.
• This allows solutes to move through water and water to pass through membrane channels - essential for transport.

• Water has a very high heat capacity - it absorbs a lot of heat without a big temperature change.
• Water has a high heat of vaporization - evaporation from skin causes cooling (sweating).
• This is why the body uses water to dissipate heat from high-energy areas like the brain into the blood.

2. Body Water Compartments and Electrolytes

3. The pH of Water - The Concept of pH

H₂O ⇌ H⁺ + OH⁻

pH = -log₁₀ [H⁺]

4. Acids and Bases

• Acid = produces H⁺ ions in water (e.g., HCl → H⁺ + Cl⁻)
• Base = produces OH⁻ ions in water (e.g., NaOH → Na⁺ + OH⁻)

• Acid = a proton (H⁺) donor
• Base = a proton (H⁺) acceptor

H⁺ + OH⁻ → H₂O

5. The Ka and pKa - Measuring Acid Strength

HA ⇌ H⁺ + A⁻

Ka = [H⁺][A⁻] / [HA]

• A higher Ka = stronger tendency to give up protons = stronger acid.
• The pKa = -log(Ka). A lower pKa = stronger acid.
• At a pH equal to the pKa, the acid is 50% dissociated (equal amounts of HA and A⁻).

6. The Henderson-Hasselbalch Equation

pH = pKa + log ([A⁻] / [HA])

pH = 6.1 + log ([HCO₃⁻] / [H₂CO₃])

• When [A⁻] = [HA], log(1) = 0, so pH = pKa.
• The ratio of conjugate base to acid determines the pH.
• Clinicians use this to understand and correct acid-base disorders (e.g., diagnosing metabolic acidosis vs. respiratory alkalosis from blood gas results).

7. Buffers - The Body's pH Defenders

• If you add H⁺ (acid) → the conjugate base (A⁻) absorbs it: A⁻ + H⁺ → HA
• If you add OH⁻ (base) → the weak acid donates H⁺: HA + OH⁻ → A⁻ + H₂O

1. The pKa relative to the solution's pH (pKa should be close to the pH you want to maintain)
2. The concentration of the buffer

• CO₂ from respiration → dissolves in water → carbonic acid (H₂CO₃)
• Lactic acid (from anaerobic exercise)
• Ketone bodies (acetoacetate, β-hydroxybutyrate) - from fat metabolism
• Sulfuric acid - from metabolism of sulfur-containing amino acids

• Lungs: Expire CO₂ (removes carbonic acid)
• Kidneys: Excrete H⁺ as NH₄⁺ (ammonium) and other ions

LECTURES 2 & 3 - Biomolecules (Standard Med 1001 Topics)

CARBOHYDRATES

• Exists in ring form (pyranose) in solution - alpha-glucose and beta-glucose differ in the position of -OH on carbon 1.
• Enters cells via glucose transporters (GLUTs).
• Broken down in glycolysis → produces ATP (energy).

• Stored form of glucose in the liver (maintains blood glucose) and muscles (energy for local use).
• Branched polymer of glucose linked by α-1,4 bonds (straight) and α-1,6 bonds (branch points).

PROTEINS AND AMINO ACIDS

• A central carbon (α-carbon)
• An amino group (-NH₂)
• A carboxyl group (-COOH)
• A hydrogen atom (-H)
• A variable side chain (-R) - this is what makes each amino acid unique

LIPIDS

• Saturated: no double bonds between carbons (e.g., palmitic acid, stearic acid) - solid at room temperature (butter, lard)
• Unsaturated: one or more double bonds (e.g., oleic acid = monounsaturated, linoleic acid = polyunsaturated) - liquid at room temperature (olive oil)
• Essential fatty acids (must come from diet): linoleic acid (omega-6), alpha-linolenic acid (omega-3)

• Primary energy storage in adipose tissue (fat cells)
• Yield more than twice as much energy per gram as carbohydrates (9 kcal/g vs. 4 kcal/g)

• Amphipathic: have a hydrophilic head and hydrophobic tails
• This property is why they form the cell membrane bilayer - tails face inward (away from water), heads face outward (toward water)
• Most common example: phosphatidylcholine (lecithin)

• Component of cell membranes (regulates fluidity)
• Precursor of steroid hormones (cortisol, testosterone, estrogen, aldosterone)
• Precursor of bile acids (for fat digestion)
• Precursor of vitamin D

• Important in brain and nerve cell membranes
• Myelin sheath of neurons contains sphingomyelin

NUCLEIC ACIDS

1. A pentose sugar (5-carbon sugar):
   • DNA uses deoxyribose (lacks -OH on carbon 2)
   • RNA uses ribose (has -OH on carbon 2)
2. A nitrogenous base:
   • Purines (double ring): Adenine (A), Guanine (G)
   • Pyrimidines (single ring): Cytosine (C), Thymine (T) in DNA; Uracil (U) replaces Thymine in RNA
3. One or more phosphate groups

• A pairs with T (in DNA) / U (in RNA) via 2 hydrogen bonds
• G pairs with C via 3 hydrogen bonds (stronger)

• Double helix - two antiparallel strands wound around each other
• Deoxyribose-phosphate forms the backbone (hydrophilic, on outside)
• Bases pair in the interior via hydrogen bonds
• Right-handed helix (B-DNA is the standard form)

DNA → (Transcription) → mRNA → (Translation) → Protein

• A nucleotide with THREE phosphate groups
• The universal energy currency of the cell
• The bond between the second and third phosphate is high-energy - breaking it releases ~7.3 kcal/mol, which cells use to drive reactions

KEY CLINICAL CONNECTIONS SUMMARY

• Basic Medical Biochemistry: A Clinical Approach, 6th edition (Marks et al.) - Chapter 4: Water, Acids, Bases, and Buffers
• BAU International University Med 1001 Course Syllabus
• Lecture 1 slide content (MS Elene Bezhanidze, BAU International)

Note for you: Since Lectures 2 and 3 were stored as image-based slides that could not be text-extracted, I covered the standard Med 1001 topics. If you can share what specific topics those lectures cover, I can go deeper into any of them with even more detail.> Important note about your PDFs: All three lecture files are image-based slide decks (the text is embedded in images, not as selectable text). I was able to extract only the title from Lecture 1. I've used the BAU International Med 1001 course syllabus, your visible slide content, and the authoritative textbook Basic Medical Biochemistry: A Clinical Approach (6e) to give you the most accurate and complete explanation of what this course covers.

Med 1001: Molecular Basis of Cell - Biochemistry

Complete Study Notes for First-Year MBBS Students

Lecturer: MS Elene Bezhanidze | BAU International University

LECTURE 1 - Water, Acids, Bases, and pH

Why Should a Medical Student Care About This?

1. Water - Structure and Properties

• The oxygen end carries a partial negative charge (δ-).
• The two hydrogen ends carry partial positive charges (δ+).

• Strength: only ~4 kcal/mol (about 1/20th of a covalent bond)
• Duration: each bond lasts only ~10 picoseconds (10 × 10⁻¹² seconds)
• They break and re-form constantly - this is why water flows (liquidity)

• Na⁺ (positive ion) → surrounded by the negative (oxygen) ends of water - called a hydration shell
• Cl⁻ (negative ion) → surrounded by the positive (hydrogen) ends
• Glucose, ATP, proteins → all polar → all dissolve easily in water

• High heat capacity: water absorbs a lot of heat without a large temperature rise - protects organs from temperature fluctuations
• High heat of vaporization: evaporating sweat cools the body (skin cooling)
• High thermal conductivity: heat from the brain and muscles is distributed via blood water throughout the body

2. Body Water Compartments and Electrolytes

• ECF is further divided into plasma (in blood vessels) and interstitial fluid (between cells).
• The unequal distribution of Na⁺ and K⁺ is maintained by the Na⁺/K⁺-ATPase pump, which uses ATP to pump 3 Na⁺ out and 2 K⁺ in for each cycle.
• This gradient is what allows nerve impulses and muscle contraction.

3. The pH Scale

H₂O ⇌ H⁺ + OH⁻

pH = -log₁₀ [H⁺]

• Arterial blood: 7.35 - 7.45
• Venous blood: ~7.32
• Intracellular: ~7.0-7.2
• Urine: 4.5-8.0 (varies)
• Gastric juice: 1.5-3.5

4. Acids and Bases

• Acid = a proton (H⁺) donor
• Base = a proton (H⁺) acceptor

HCl → H⁺ + Cl⁻ (HCl donates H⁺ → it is an acid)

NaOH → Na⁺ + OH⁻ (OH⁻ accepts H⁺ → OH⁻ is a base)

OH⁻ + H⁺ → H₂O (neutralisation - this was on your slide!)

5. Ka, pKa, and the Henderson-Hasselbalch Equation

HA ⇌ H⁺ + A⁻

Ka = [H⁺][A⁻] / [HA]

• Higher Ka → stronger tendency to donate protons → stronger acid
• pKa = -log(Ka) → lower pKa = stronger acid

pH = pKa + log ([A⁻] / [HA])

pH = 6.1 + log ([HCO₃⁻] / [H₂CO₃])

6. Buffers - The Body's pH Protection System

• Add acid (H⁺) → the conjugate base absorbs it:

  A⁻ + H⁺ → HA (H⁺ is "mopped up" - pH barely changes)

• Add base (OH⁻) → the weak acid donates H⁺ to neutralise it:

  HA + OH⁻ → A⁻ + H₂O

1. pKa close to the target pH (a buffer works best within ±1 pH unit of its pKa)
2. High concentration (more buffer = greater capacity to absorb H⁺ or OH⁻)

• CO₂ (from cellular respiration) → + H₂O → H₂CO₃ (carbonic acid) - the largest source
• Lactic acid (from anaerobic metabolism in muscles)
• Ketone bodies (acetoacetic acid, β-hydroxybutyric acid) - from fat metabolism
• Sulfuric acid - from metabolism of sulfur-containing amino acids (methionine, cysteine)

• Lungs: Breathe out CO₂ (reduces carbonic acid)
• Kidneys: Excrete H⁺ as ammonium (NH₄⁺) and in combination with phosphate

LECTURES 2 & 3 - Biomolecules

CARBOHYDRATES

• Formula: C₆H₁₂O₆
• In solution, glucose exists as a ring (pyranose form)
• α-glucose and β-glucose differ only in whether the -OH group on carbon 1 points down (α) or up (β) - this tiny difference has massive consequences: starch (α-linkages) is digestible; cellulose (β-linkages) is not
• Normal blood glucose: 3.9-6.1 mmol/L (70-110 mg/dL)

• The storage form of glucose in humans
• Liver glycogen: maintains blood glucose between meals (up to ~100g)
• Muscle glycogen: provides fuel for the muscle itself (up to ~400g)
• Highly branched polymer of glucose via α-1,4 bonds (linear) and α-1,6 bonds (branch points)

• Diabetes mellitus - failure to regulate blood glucose
• Lactose intolerance - deficiency of lactase enzyme (cannot break lactose into glucose + galactose)
• Glycogen storage diseases - enzyme defects in glycogen synthesis/breakdown (e.g., Von Gierke disease)

PROTEINS AND AMINO ACIDS

1. An amino group (-NH₂)
2. A carboxyl group (-COOH)
3. A hydrogen atom (-H)
4. A variable side chain (-R) - this defines each amino acid's identity and properties

• At low pH (acidic): -NH₃⁺ and -COOH (both protonated)
• At neutral/physiological pH: zwitterion - -NH₃⁺ and -COO⁻ (both charges present simultaneously)
• At high pH (basic): -NH₂ and -COO⁻ (both deprotonated)

• Non-polar/hydrophobic: Glycine, Alanine, Valine, Leucine, Isoleucine, Proline, Phenylalanine, Tryptophan, Methionine
• Polar/uncharged: Serine, Threonine, Cysteine, Tyrosine, Asparagine, Glutamine
• Positively charged (basic): Lysine, Arginine, Histidine
• Negatively charged (acidic): Aspartate, Glutamate

Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine Mnemonic: "PVT TIM HaLL" (Private Tim Hall)

• Causes: heat (boiling), strong acids/bases, organic solvents, heavy metals
• Example: boiling an egg white (albumin protein denatures irreversibly - turns white and solid)
• Clinical note: High fever can denature enzymes, disrupting metabolism. Sterilisation uses heat to denature bacterial proteins.
• Sickle cell disease: A single amino acid change in hemoglobin (glutamate → valine at position 6 of the β-chain) causes the protein to polymerise in low-oxygen conditions, distorting red blood cells into a sickle shape.

LIPIDS

• Structure: one glycerol molecule + three fatty acids joined by ester bonds
• Primary form of energy storage in adipose tissue
• Yield 9 kcal/g (vs. 4 kcal/g for carbohydrates and proteins) - twice as energy-dense
• Mobilised by hormone-sensitive lipase when energy is needed

• Structure: glycerol + 2 fatty acids + phosphate group + polar "head" group
• Amphipathic: one end is hydrophilic (polar head), the other is hydrophobic (fatty acid tails)
• This dual nature drives the formation of the cell membrane lipid bilayer:
  • In water, phospholipids spontaneously arrange so tails face inward (away from water) and heads face outward
• Most important example: Phosphatidylcholine (lecithin)
• Sphingomyelin (a sphingophospholipid) is a major component of the myelin sheath of neurons

• A sterol - has a characteristic 4-ring (steroid) structure
• An essential component of all animal cell membranes:
  • At high temperatures: reduces membrane fluidity (keeps it from melting)
  • At low temperatures: prevents packing (keeps it from solidifying)
  • This is called membrane fluidity regulation
• Precursor of:
  • Steroid hormones: cortisol, aldosterone, testosterone, estrogen, progesterone
  • Bile acids: needed for fat digestion in the small intestine
  • Vitamin D: made in skin upon UV light exposure
• Clinical note: Statins (e.g., atorvastatin, simvastatin) block HMG-CoA reductase (the rate-limiting enzyme of cholesterol synthesis in the liver), reducing LDL cholesterol and cardiovascular risk.

NUCLEIC ACIDS

1. A pentose sugar (5-carbon ring):
   • DNA → 2'-deoxyribose (no -OH at carbon 2)
   • RNA → ribose (has -OH at carbon 2)
2. A nitrogenous base:
   • Purines (double-ring): Adenine (A), Guanine (G) - in both DNA and RNA
   • Pyrimidines (single-ring): Cytosine (C) - in both; Thymine (T) - DNA only; Uracil (U) - RNA only
   • Memory trick: PURe As Gold (Purines = Adenine + Guanine)
3. Phosphate group(s)

• Nucleoside = sugar + base (no phosphate)
• Nucleotide = sugar + base + 1-3 phosphate groups
• ATP = adenosine triphosphate → the cell's energy currency

• Two anti-parallel polynucleotide strands wound around each other in a right-handed helix
• The sugar-phosphate backbone is on the outside (hydrophilic, faces water)
• The bases are on the inside, paired via hydrogen bonds:
  • A pairs with T: 2 hydrogen bonds (A=T)
  • G pairs with C: 3 hydrogen bonds (G≡C) - stronger
• The two strands are antiparallel: one runs 5'→3', the other 3'→5'
• Chargaff's Rule: In any DNA molecule, %A = %T and %G = %C

DNA → (Transcription) → mRNA → (Translation) → Protein

• Replication: DNA → DNA (before cell division; each strand serves as a template)
• Transcription: DNA → mRNA (in the nucleus; only one strand is the template)
• Translation: mRNA → Protein (at the ribosome; codons specify amino acids)

• Each codon = 3 consecutive nucleotide bases on mRNA = codes for one amino acid
• There are 4³ = 64 possible codons for 20 amino acids - the code is redundant (multiple codons can code for the same amino acid)
• Start codon: AUG (codes for methionine; signals start of translation)
• Stop codons: UAA, UAG, UGA (signal end of translation - no amino acid added)

• ATP has three phosphate groups in sequence. Breaking the bond between the 2nd and 3rd phosphate releases ~7.3 kcal/mol:

  ATP + H₂O → ADP + Pᵢ + energy

• This energy drives virtually all cellular processes: muscle contraction, ion pumping, protein synthesis, etc.

KEY CLINICAL CONNECTIONS

QUICK-REFERENCE FORMULAS

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