Human Physiology: Protein Synthesis and Cellular Metabolism Study Notes

Protein Synthesis

Overview of Protein Synthesis

Protein synthesis is a fundamental cellular process in which genetic information encoded in DNA is used to produce functional proteins. This process occurs in two main stages: transcription and translation.

• Transcription: The genetic code in DNA is transcribed to form complementary messenger RNA (mRNA) in the nucleus.

• Translation: The mRNA moves from the nucleus to the cytoplasm, where ribosomes translate it to form the correct amino acid sequence of a protein.

• Example: Hemoglobin synthesis in red blood cells.

Transcription: DNA to mRNA

Transcription is the process by which a segment of DNA is copied into mRNA by the enzyme RNA polymerase.

• DNA Structure: DNA consists of two separate strands. One strand contains genes and serves as the template for mRNA synthesis.

• Promoter Sequence: A specific base sequence in DNA where RNA polymerase binds to initiate transcription.

• RNA Polymerase: Binds to the promoter, unwinds DNA, and catalyzes the formation of mRNA.

• Post-Transcriptional Processing: Pre-mRNA undergoes modifications in the nucleus before becoming mature mRNA:

  • Introns: Non-coding regions removed from pre-mRNA.

  • Exons: Coding regions joined together to form mature mRNA.

• After processing, mRNA exits the nucleus and enters the cytoplasm.

• Equation: $\text{DNA} \xrightarrow{\text{transcription}} \text{mRNA}$

Translation: mRNA to Protein

Translation is the process by which ribosomes synthesize proteins using the sequence of codons in mRNA.

• Ribosomes: Cellular structures that facilitate the assembly of amino acids into polypeptides.

• Initiation: Ribosomal subunits and initiation factors assemble at the start codon (AUG) on mRNA.

• tRNA: Transfer RNA molecules bring specific amino acids to the ribosome, matching mRNA codons with their anticodons.

• Peptidyl Transferase: Enzyme that catalyzes peptide bond formation between amino acids.

• Elongation: The ribosome moves along mRNA, adding amino acids to the growing polypeptide chain.

• Termination: Occurs when a stop codon is reached; the completed polypeptide is released.

• Equation: $\text{mRNA} \xrightarrow{\text{translation}} \text{Protein}$

• Example: Synthesis of insulin in pancreatic cells.

Summary Table: Key Steps in Protein Synthesis

Step	Location	Main Molecules Involved	Key Events
Transcription	Nucleus	DNA, RNA polymerase, pre-mRNA	DNA is copied to mRNA
Post-Transcriptional Processing	Nucleus	pre-mRNA, splicing enzymes	Introns removed, exons joined
Translation	Cytoplasm	mRNA, ribosomes, tRNA, amino acids	Protein is synthesized

Cellular Metabolism

Overview of Metabolism

Metabolism refers to the sum total of all chemical reactions that occur in cells, enabling growth, energy production, and maintenance of cellular functions. Metabolic pathways are sequences of reactions where the product of one reaction serves as the substrate for the next.

• Anabolism: Synthesis of larger molecules from smaller ones (e.g., protein synthesis, glycogen formation).

• Catabolism: Breakdown of larger molecules into smaller ones (e.g., protein breakdown, glycogenolysis).

• Example: Glucose metabolism in muscle cells.

Types of Metabolic Reactions

• Hydrolysis: Water is used to break bonds in molecules, producing smaller units (e.g., peptide bond breakdown).

• Condensation: Joining of smaller molecules to form larger ones, releasing water (e.g., formation of proteins from amino acids).

• Phosphorylation: Addition of a phosphate group to a molecule, often using ATP.

• Dephosphorylation: Removal of a phosphate group, often releasing energy.

• Oxidation-Reduction (Redox) Reactions: Transfer of electrons between molecules; always coupled.

Energy in Biological Systems

• Kinetic Energy: Energy of motion (e.g., thermal, electrical).

• Potential Energy: Stored energy that can be converted to kinetic energy (e.g., chemical energy in bonds).

• First Law of Thermodynamics: Energy cannot be created or destroyed; it can only change forms.

• Second Law of Thermodynamics: Natural processes increase the disorder (entropy) of a system.

Enzymes and Reaction Rates

Enzymes are biological catalysts that increase the rate of chemical reactions by lowering activation energy.

• Enzyme-Substrate Complex: Enzyme binds to substrate to facilitate reaction.

• Specificity: Enzymes are specific to their substrates due to complementary shapes.

• Models of Enzyme Binding:

  • Lock-and-Key Model: Substrate fits perfectly into the enzyme's active site.

  • Induced Fit Model: Enzyme changes shape to fit the substrate upon binding.

• Cofactors: Non-protein components required for enzyme activity (e.g., iron, zinc).

• Coenzymes: Organic molecules that assist enzymes (e.g., NAD, FAD, CoA).

• Factors Affecting Enzyme Activity: Catalytic rate, substrate concentration, enzyme concentration, affinity for substrate.

• Equation: $\text{E} + \text{S} \rightleftharpoons \text{ES} \rightarrow \text{E} + \text{P}$

ATP and Energy Storage

ATP Synthesis and Hydrolysis

Adenosine triphosphate (ATP) is the primary energy carrier in cells. It is synthesized from adenosine diphosphate (ADP) and inorganic phosphate (Pi) via condensation reactions and is hydrolyzed to release energy for cellular work.

• ATP Synthesis: $\text{ADP} + \text{Pi} \rightarrow \text{ATP} + \text{H}_2\text{O}$

• ATP Hydrolysis: $\text{ATP} + \text{H}_2\text{O} \rightarrow \text{ADP} + \text{Pi}$

• Example: Muscle contraction uses ATP hydrolysis for energy.

Glucose Metabolism

Glycolysis

Glycolysis is a metabolic pathway consisting of 10 reactions that convert glucose into pyruvate in the cytosol.

• Reactants: 1 glucose molecule

• Products: 2 pyruvate, 2 net ATP, 2 NADH

• Equation: $\text{Glucose} + 2\text{NAD}^+ + 2\text{ADP} + 2\text{Pi} \rightarrow 2\text{Pyruvate} + 2\text{NADH} + 2\text{ATP} + 2\text{H}_2\text{O}$

• Example: Energy production in muscle cells during exercise.

Krebs Cycle (Citric Acid Cycle)

The Krebs cycle occurs in the mitochondrial matrix and completes the oxidation of glucose derivatives, producing NADH, FADH2, and ATP.

• Reactants: Acetyl-CoA, NAD+, FAD, ADP, Pi

• Products: CO2, NADH, FADH2, ATP

• Equation: $\text{Acetyl-CoA} + 3\text{NAD}^+ + \text{FAD} + \text{ADP} + \text{Pi} \rightarrow 2\text{CO}_2 + 3\text{NADH} + \text{FADH}_2 + \text{ATP}$

Oxidative Phosphorylation and Electron Transport Chain (ETC)

Oxidative phosphorylation is the process by which ATP is synthesized using energy released by electrons transferred through the ETC in the inner mitochondrial membrane.

• NADH and FADH2: Donate electrons to the ETC.

• ETC: Series of protein complexes that transfer electrons and pump hydrogen ions to create a gradient.

• ATP Synthase: Enzyme that uses the hydrogen ion gradient to synthesize ATP.

• Equation: $\text{ADP} + \text{Pi} \rightarrow \text{ATP}$ (driven by proton gradient)

• Total ATP Yield: Up to 32 ATP per glucose molecule (including glycolysis, Krebs cycle, and oxidative phosphorylation).

Summary Table: ATP Yield from Glucose Metabolism

Pathway	ATP Produced
Glycolysis	2
Krebs Cycle	2
Oxidative Phosphorylation	28
Total	32

Other Metabolic Pathways

Glycogenesis and Glycogenolysis

• Glycogenesis: Formation of glycogen from glucose for storage in liver and muscle cells.

• Glycogenolysis: Breakdown of glycogen to release glucose when energy is needed.

Gluconeogenesis

• Definition: Synthesis of new glucose from non-carbohydrate sources (e.g., amino acids, glycerol, lactate).

• Importance: Maintains blood glucose levels, especially for brain and nervous tissue.

Lipid Metabolism

• Triglyceride Storage: Fats are stored as triglycerides, providing more energy per gram than carbohydrates.

• Lipolysis: Breakdown of triglycerides into fatty acids and glycerol.

• Beta-Oxidation: Fatty acids are catabolized to acetyl-CoA, which enters the Krebs cycle.

• Ketogenesis: Excessive breakdown of fats leads to ketone body formation, which can be used as an alternative energy source but may cause ketoacidosis if excessive.

• Lipogenesis: Synthesis of fats from carbohydrates and proteins.

Protein Metabolism

• Proteolysis: Breakdown of proteins into amino acids.

• Deamination: Removal of amino group from amino acids, producing ammonia (excreted in urine).

• Carbon Skeletons: Can be converted to pyruvate, acetyl-CoA, or Krebs cycle intermediates for energy production.

Additional info: These notes expand on the provided lecture slides and images, adding definitions, equations, and examples for clarity and completeness.