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Announcements (Page 1)

• There will be no lecture or student hours on Friday of this week.

• Pre- and post-class questions will continue as usual to help reinforce learning.

• The lecture content being used is recorded from Fall 2024.

• Times to review exam questions are scheduled in 200 Burrill Hall:

  • Today: 3:30-5:00 PM

  • Tuesday: 10:30-Noon

  • Thursday: 9:30-11:00 AM

Course Overview (Pages 2-3)

• MCB 150: The Molecular and Cellular Basis of Life provides foundational knowledge in molecular biology and cell physiology.

• Lecture 11 focuses on Cellular Respiration, a vital metabolic process used by cells to convert nutrients into energy.

• Phase 2 of cellular respiration involves Pyruvate Oxidation and the Krebs Cycle (Citric Acid Cycle), which are critical for energy extraction from glucose.

Glycolysis and Krebs Cycle (Page 4)

• Phase 1: Glycolysis converts one molecule of glucose into two molecules of pyruvate, releasing a small amount of energy (2 ATP) and generating electron carriers (NADH).

• The net results of Phase 1 and 2 for each glucose molecule include:

  • 2 NADH (from Glycolysis) and 6 NADH from the Krebs Cycle.

  • 2 FADH2 produced during two turns of the Krebs Cycle.

  • 2 ATP are directly produced (one from each turn of Krebs).

• Issues at the end of the Krebs Cycle include:

  • The regeneration of NAD+ is crucial as depletion leads to a halt in the Krebs Cycle.

  • Excess NADH and FADH2 must be oxidized for the processes to advance efficiently.

  • There is an energy transfer to ATP that has yet to occur in the cycle's direct processes.

• Aerobic respiration requires oxygen (O2) for the electron transport chain, while the Krebs Cycle is indirectly reliant on oxygen availability due to its connection with the Electron Transport Chain (ETC).

Oxidative Phosphorylation and Electron Transport Chain (Pages 5-7)

• The Electron Transport Chain (ETC) is a series of protein complexes located in the inner mitochondrial membrane where electron transfer occurs.

• NADH donates electrons to the first carrier, enabling its re-oxidation back to NAD+. Electrons are successively passed along the electron carriers in the chain.

• As electrons are transferred, energy is released, allowing protons (H+) to pump across the membrane, creating a proton gradient.

• Oxygen serves as the final electron acceptor in the chain, leading to the formation of water (H2O) when it combines with protons.

• FADH2 contributes to the ETC but at a lower rate, resulting in less proton pumping compared to NADH.

• The essential result of the ETC is the restoration of cofactors (like NAD+) and establishment of a proton gradient, but ATP is not produced yet.

ATP Production (Page 7)

• The overall reaction for glucose oxidation can be summarized as:

  Glucose + 6O2 → 6CO2 + 6H2O

• Theoretical ATP production estimates from cellular respiration include:

  • Glycolysis: 2 ATP directly + 4 ATP equivalent from each NADH.

  • Krebs cycle: 2 ATP directly + 24 ATP equivalent from 6 NADH + 4 ATP equivalent from 2 FADH2.

  • This totals a theoretical production of 36 ATP from one glucose molecule under ideal conditions.

Fermentation (Pages 8-11)

• Lecture 12 discussed Fermentation and regulation of cellular metabolism under anaerobic conditions.

• Cellular respiration can occur without oxygen, relying solely on glycolysis and through fermentation to regenerate NAD+ from NADH.

• Types of Fermentation:

  • Yeast Fermentation: Pyruvate is converted to Acetaldehyde, then to Ethanol.

  • Lactic Acid Fermentation: In muscle cells and certain bacteria, pyruvate is converted to Lactic Acid.

Enzyme Regulation (Pages 12-15)

• Both catabolic and biosynthetic pathways are strictly regulated to optimize energy and material resource use, avoiding waste.

• Regulation occurs through:

  • Variation in enzyme amounts (increased synthesis in response to need).

  • Use of allosteric regulators that bind to sites other than the active sites affecting enzyme activity.

  • Feedback inhibition where the final product of a pathway inhibits an earlier step to prevent overproduction (e.g., ATP inhibiting PFK in glycolysis).

The Central Dogma (Pages 15-18)

• The molecular structure of DNA contains the genetic code necessary for the synthesis of proteins.

• Transcription involves the process of converting DNA to RNA, while Translation converts RNA into proteins.

• Chargaff's Rules establish base pairs' relationships: adenine (A) pairs with thymine (T), and cytosine (C) pairs with guanine (G).

• The pioneering work of Rosalind Franklin enabled the understanding of DNA’s helical structure, utilized in the model proposed by Watson and Crick.

DNA Structure and Base Pairing (Pages 18-19)

• DNA bases pair through hydrogen bonds:

  • Purine bases (A, G) pair with pyrimidine bases (C, T) ensuring a uniform helical width.

• Watson-Crick base pairing rules dictate:

  • G pairs with C (three hydrogen bonds).

  • A pairs with T (two hydrogen bonds), providing stability to the DNA structure.

• DNA is described as double-stranded, antiparallel, and consists of complementary strands allowing for precise replication.

DNA Replication (Pages 20-27)

• DNA replication begins with unwinding at the Origin of Replication (ori), where helicase enzymes split the strands.

• The semi-conservative model explains that each newly formed DNA helix comprises one parental strand and one synthesized new strand.

• The leading strand is synthesized continuously heading towards the replication fork, while the lagging strand is synthesized in short segments called Okazaki fragments due to the antiparallel nature of DNA.

• Primase synthesizes RNA primers, allowing DNA polymerase to initiate DNA synthesis.

• DNA ligase connects Okazaki fragments and seals nicks in the sugar-phosphate backbone to complete the newly synthesized DNA strand.

Transcription in Prokaryotes (Pages 47-52)

• Transcription is conducted by RNA Polymerase, which synthesizes mRNA based on the DNA template.

• The steps in transcription include:

  1. Promoter recognition by sigma factors that recruit RNA Polymerase to specific sites on DNA.

  2. Initiation where RNA Polymerase begins RNA synthesis.

  3. Elongation where RNA polymer grows the mRNA strand by adding nucleotides.

  4. Termination which can occur through Rho-dependent or intrinsic mechanisms, signaling mRNA synthesis completion.

• In prokaryotes, bacterial mRNAs usually contain multiple ribosome binding sites, making them polycistronic, allowing simultaneous translation of multiple proteins.

RNA Processing and Translation (Pages 60-70)

• Eukaryotic mRNA processing involves several steps to mature primary transcripts into functional mRNA:

  • Intron removal and exon splicing to join coding regions.

  • Addition of a 5' cap for stability and recognition by ribosomes, and a poly-A tail for nuclear export and translation efficiency.

• Multiple types of RNA are generated during transcription, including mRNA (messenger RNA), rRNA (ribosomal RNA), and tRNA (transfer RNA), each serving distinct roles in protein synthesis.

• Translation involves converting mRNA into a polypeptide chain, utilizing tRNA to bring amino acids to ribosomes, which serve as the sites for protein assembly.

Cellular respiration is a metabolic process that converts nutrients into energy within cells, primarily through glycolysis, the Krebs cycle, and the electron transport chain. Glycolysis breaks down glucose into pyruvate, generating ATP and NADH. The Krebs cycle further processes pyruvate, producing electron carriers (NADH and FADH2) and ATP while regenerating NAD+ for continuous operation. The electron transport chain located in the inner mitochondrial membrane is crucial for ATP production, utilizing oxygen as the final electron acceptor to form water and create a proton gradient for ATP synthesis via oxidative phosphorylation. Under anaerobic conditions, cells can undergo fermentation to regenerate NAD+ and continue ATP production.