Biochem Oct. 20th

Assignment Deadline

• Team assignment deadline is tonight at 11:59 PM.

• Submission Requirements:

  • Submit the full assignment (infographic or video) to PeerMark (instructions available on the assignment page).

  • Submit a text-only version (not checked for plagiarism).

Recap of Last Lecture

• Previous discussion on the electron transport chain and how electrons from NADH and QH2 contribute to ATP production.

Electron Transport Chain Mechanics

• Electrons from NADH and other sources help create an electrochemical gradient across the inner mitochondrial membrane:

  • Protons (H+) are pumped from the matrix to the intermembrane space.

  • This leads to:

  • Concentration difference (high proton concentration in intermembrane space and low in the matrix).

  • Electrical potential difference (net positive charge in intermembrane space, net negative in the matrix).

  • Estimated pH difference of approximately 0.7.

  • The electron transport chain involves four major protein complexes:

  • Complex I (NADH dehydrogenase): Accepts electrons from NADH, pumps 4 H+.

  • Complex II (Succinate dehydrogenase): Accepts electrons from QH2 (FADH2), does not pump protons directly.

  • Complex III (Cytochrome c reductase): Accepts electrons from ubiquinone, pumps 4 H+.

  • Complex IV (Cytochrome c oxidase): Accepts electrons from cytochrome c, pumps 2 H+ and reduces O2 to H2O.

Chemiosmotic Hypothesis

• Proposed by Peter Mitchell in 1961:

  • Suggested that proton concentration difference across the mitochondrial membrane is a source of energy for ATP synthesis.

  • Initially, scientists believed ATP production depended on high-energy phosphate compounds.

  • Despite skepticism and Mitchell's abrasive personality, experiments eventually supported his hypothesis.

  • ATP Synthase found to facilitate ATP synthesis using the proton gradient.

Structure of ATP Synthase

• Known as F1F0 ATP synthase:

  • F0 component: integral membrane part responsible for transferring protons.

  • F1 component: peripheral proteins involved in ATP synthesis.

  • Components of F1:

  • Subunits: $5\alpha$, $\beta$, $\gamma$, $\delta$, $\epsilon$.

  • Functionality relies on the interaction between protons and the c ring in the F0 part.

Proton Channel Mechanism

• Each c subunit of ATP synthase has proton binding sites:

  • Protons accumulate from the intermembrane space and must rotate through half channels to enter the matrix.

  • The proton movement necessitates a rotational mechanism within the c subunit, akin to a ratchet.

Mechanism of ATP Synthesis

• Active sites for ATP synthesis located in the $\beta$ subunits of ATP synthase:

  • When the $\gamma$ subunit rotates, it alters the shape of the active sites, allowing ADP and inorganic phosphate (Pi) to be converted to ATP. This process is known as the binding change mechanism (proposed by Paul Boyer), where the $\beta$ subunits cycle through three conformational states: open (releases ATP), loose (binds ADP and Pi), and tight (converts ADP and Pi to ATP).

  • Each complete $360^\circ$ rotation leads to the synthesis of three ATP molecules through interactions with the active sites.

Video Representation of ATP Synthase

• Video confirms the rotary motion of ATP synthase and its role in ATP production from proton flow.

• Revelation that ATP synthase can operate in reverse under certain conditions.

Nobel Prizes in ATP Research

• Both Paul Boyer and John Walker recognized for their significant contributions regarding ATP synthase structure and function (1997 Nobel Prize).

Energy Yield from Electron Transport Chain

• NADH and QH2 contribute differently to ATP yield:

  • Each NADH (entering at Complex I) provides approximately 2.5 ATP after proton export and ATP production because its electrons pass through Complexes I, III, and IV, leading to more protons pumped.

  • Each QH2 (entering at Complex II) results in approximately 1.5 ATP because its electrons bypass Complex I, initiating proton pumping only at Complexes III and IV, thus pumping fewer protons.

• Discussion surrounding gluconeogenesis and glycolysis relating to ATP production from NADH and QH2.

Active Transport Mechanisms

• Import/Export of ATP and ADP involves:

  • Adenine nucleotide translocase (ANT): An antiporter mechanism for ATP out and ADP back into mitochondria, coupled with the electrical potential across the membrane.

  • Phosphate translocase: A symporter mechanism for importing phosphate (Pi) coupled with proton movement from high to low concentration into the matrix.

Basics of Fatty Acid Metabolism

• In conditions of low blood glucose, muscle cells utilize fatty acids and glucose for energy.

• Beta-oxidation process in mitochondria breaks down fatty acids into acetyl CoA, generating ATP.

• Triacylglycerol (triglycerides) is broken down into glycerol and fatty acids, with glycerol potentially converted back into glucose through gluconeogenesis.

Summary of Energy Production from Glucose

• Key reactions from glycolysis and the citric acid cycle leads to a theoretical maximum of 32 ATP per glucose molecule, emphasizing greater efficiency compared to fermentation (2 ATP per glucose