60 Flashcard Set for Q4

Why is the ribosome considered a "ribozyme" rather than just a structural complex?

Because the ribosomal RNA (rRNA) component, not the protein, contains the catalytic activity required to synthesize proteins.[cite: 1]

Physically, how does protein synthesis proceed directionally?

New amino acids are added to the C-terminus, meaning synthesis strictly proceeds from the N-terminus to the C-terminus.[cite: 1]

Mechanistically, how does the Shine-Dalgarno sequence function?

It acts as an upstream physical landing pad, analogous to a DNA promoter, that aligns the 30S initiation complex perfectly with the AUG start codon.[cite: 1]

Why does the 30S initiation complex form before the 50S subunit attaches?

It ensures the mRNA, tRNA^fMet, and initiation factors are correctly positioned before locking the massive 70S ribosome together.[cite: 1]

What thermodynamic event forces the release of initiation factors (IF-1 and IF-3)?

The binding of the 50S large subunit triggers the hydrolysis of GTP, providing the energy to eject the initiation factors.[cite: 1]

Conceptually, what is the role of the ribosomal A-site?

It is the "Acceptor" site that physically reads the mRNA codon and accepts the incoming, charged aminoacyl-tRNA.[cite: 1]

Conceptually, what is the role of the ribosomal P-site?

It is the "Peptidyl" site that holds the tRNA attached to the growing polypeptide chain during catalysis.[cite: 1]

Mechanistically, how is a peptide bond actually formed in the ribosome?

The alpha-amino nitrogen (nucleophile) in the A-site attacks the carbonyl carbon (electrophile) of the peptidyl-tRNA in the P-site.[cite: 1]

What happens to the polypeptide chain during the nucleophilic attack in the ribosome?

The entire protein chain is physically transferred from the P-site tRNA onto the newly arrived amino acid in the A-site.[cite: 1]

What is the physical mechanism of ribosomal translocation?

The entire complex shifts exactly one codon down the mRNA, moving the empty tRNA to the E-site and the chain-holding tRNA into the P-site.[cite: 1]

Why do release factors (RF-1, RF-2) terminate translation instead of adding an amino acid?

They recognize stop codons (UAA, UAG, UGA) but are proteins rather than tRNAs, blocking elongation and forcing hydrolysis of the chain.[cite: 1]

Why is coupled translation physically possible in prokaryotes but not eukaryotes?

Prokaryotes lack a nuclear membrane, meaning ribosomes can physically latch onto mRNA and translate it while it is still being transcribed from DNA.[cite: 1]

How do eukaryotic ribosomes find the start codon without a Shine-Dalgarno sequence?

The 43S pre-initiation complex binds to the 5' 7-methyl GTP cap on the mRNA and scans down the strand to find the start site.[cite: 2]

What structural modification protects the 3' end of eukaryotic mRNA?

A poly-A tail added to the 3' untranslated region (UTR).[cite: 2]

Why is eukaryotic translation initiation structurally distinct from prokaryotes?

Eukaryotes assemble a complete 43S complex (containing met-tRNA_i) BEFORE it ever binds the mRNA, rather than building it on the strand.[cite: 2]

What structural site is suggested to be completely missing in the eukaryotic ribosome?

The E-site (exit site); uncharged tRNAs are likely ejected differently than in the 3-site prokaryotic model.[cite: 2]

Why do many inactive protein precursors have the prefix "pro-" (e.g., pro-insulin)?

It indicates the protein is trapped in an inactive state and requires a specific physical cleavage (post-translational modification) to become biologically active.[cite: 2]

Why are sugars or lipids added to proteins as post-translational modifications?

They act as molecular shipping tags, trafficking the proteins to the cell membrane for intracellular signaling or cell-cell communication.[cite: 2]

Why must protein degradation be strictly restricted to lysosomes or the proteasome?

These compartments physically quarantine destructive degradative enzymes to prevent them from randomly catabolizing healthy cellular proteins.[cite: 2]

What is the mechanistic function of Ubiquitin (Ub)?

It is a 76-amino acid "trash tag" covalently attached to mutated or misfolded proteins to condemn them to destruction by the proteasome.[cite: 2]

Why does ubiquitination require a three-enzyme cascade (E1, E2, E3)?

This bucket-brigade (activate, carry, ligate) acts as a strict regulatory checkpoint to ensure ubiquitin is only attached to specific target substrates.[cite: 2]

What is the physical basis of the N-terminal degron rule?

The specific chemical nature of the amino acid residue at the N-terminus directly dictates the protein's cellular half-life.[cite: 2]

Which N-terminal amino acids act as rapid "self-destruct" signals?

Acidic, basic, or bulky residues like R, K, H, F, or Y cause the protein to be degraded very rapidly (2-30 minutes).[cite: 2]

Which N-terminal amino acids physically stabilize a protein against degradation?

Small or stabilizing residues like M, S, A, T, V, or G allow the protein to resist degradation for hours or days.[cite: 2]

Thermodynamically, what is the difference between catabolism and anabolism?

Catabolism breaks down molecules to release energy (exergonic/oxidative), while anabolism uses energy to build molecules (endergonic/reductive).[cite: 3]

Why do biochemists use a modified standard state (Delta G naught prime)?

Standard chemistry states assume pH 0 (1.0 M H+), which is biologically irrelevant; the modified state adjusts standard conditions to a physiological pH of 7.[cite: 3]

How does the concept of equilibrium simplify standard free energy calculations?

At equilibrium, Delta G is exactly zero, allowing us to calculate the standard free energy change (Delta G naught) directly using the equilibrium constant (K_eq).[cite: 3]

Why are reactions in the middle of a metabolic pathway usually completely reversible?

They have a Delta G near zero, meaning small shifts in reactant/product concentrations easily push the reaction in either direction.[cite: 3]

Why are reactions at the beginning and end of pathways usually irreversible?

They have highly negative Delta G values, acting as strictly regulated, one-way "valves" that control the overall flow of the entire pathway.[cite: 3]

Mechanistically, how does reaction coupling drive thermodynamically unfavorable reactions?

An endergonic reaction (+Delta G) is physically linked to a highly exergonic one (-Delta G, like ATP hydrolysis) so the net energy change of the system is favorable.[cite: 3]

Why does the hydrolysis of ATP release so much energy?

Breaking the phosphate bond relieves massive electrostatic repulsion between the tightly packed negative charges of the triphosphate chain.[cite: 3]

How does resonance stabilization contribute to the high energy yield of ATP hydrolysis?

The free phosphate ion has far greater resonance stabilization once cleaved than it did when trapped in the ATP molecule, lowering the overall system energy.[cite: 3]

Is the energy from ATP hydrolysis stored in the cell like a battery?

No, the energy is not stored; the hydrolysis is immediately coupled to drive other unfavorable anabolic reactions.[cite: 3]

Why do enzymes rely on coenzymes like NADH and FADH2?

Amino acid side chains are inherently poor oxidizing/reducing agents, so enzymes use these specialized chemical tools to physically transfer electrons.[cite: 3]

In a biochemical redox reaction, what happens to the reducing agent?

The reducing agent donates its electrons and becomes oxidized in the process.[cite: 3]

In a biochemical redox reaction, what happens to the oxidizing agent?

The oxidizing agent accepts electrons and becomes reduced in the process.[cite: 3]

Thermodynamically, why does the cell invest 2 ATP in the preparation phase of glycolysis?

To phosphorylate the sugar, trapping it inside the cell and raising its free energy to prime it for the cleavage and payoff phases.[cite: 4]

What is the net chemical payoff of glycolysis per molecule of glucose?

2 molecules of pyruvate, 2 net ATP, and 2 molecules of NADH.[cite: 4]

Why is Hexokinase (Step 1) a critical metabolic control point?

It catalyzes a highly exergonic, irreversible phosphorylation and is allosterically inhibited by its own product (glucose-6-phosphate) to prevent over-accumulation.[cite: 4]

Conceptually, what is the function of Phosphofructokinase (PFK) in Step 3?

It is the major regulatory gateway of glycolysis, catalyzing a second irreversible phosphorylation that heavily commits the sugar to breakdown.[cite: 4]

How and why does ATP allosterically regulate PFK?

High ATP concentrations inhibit PFK, serving as a feedback loop that signals cellular energy is abundant and glycolysis should slow down.[cite: 4]

Why is the Aldolase reaction (Step 4) energetically unfavorable?

It acts as the reverse of an aldol condensation, forcing a stable 6-carbon sugar to split into two 3-carbon fragments.[cite: 4]

Mechanistically, why is Glyceraldehyde-3-phosphate dehydrogenase (Step 6) unique?

It captures reducing power (NADH) and phosphorylates the sugar using free inorganic phosphate (Pi) without spending any cellular ATP reserves.[cite: 4]

What is substrate-level phosphorylation?

Generating ATP by directly transferring a phosphate from a high-energy metabolic intermediate onto ADP (seen in Steps 7 and 10).[cite: 4]

Why does Enolase dehydrate 2-phosphoglycerate in Step 9?

Removing water creates phosphoenolpyruvate, a highly unstable molecule primed to forcefully transfer its phosphate to ADP in the final step.[cite: 4]

What is the thermodynamic function of Pyruvate kinase in Step 10?

It catalyzes a highly exergonic, irreversible dephosphorylation to generate ATP, thermodynamically pulling the entire second half of the pathway forward.[cite: 4]

Under anaerobic conditions, why must pyruvate be converted to lactate?

To oxidize NADH back into NAD+, which is required for Step 6 to continue running glycolysis in the absence of oxygen.[cite: 4]

Why is liver pyruvate kinase regulated by blood glucose levels?

The liver is responsible for systemic energy balance, so its enzymes must respond to global hormone signals rather than just local cellular ATP states.[cite: 4]

Why isn't gluconeogenesis simply the exact reverse of glycolysis?

The three kinase steps of glycolysis are highly exergonic and irreversible, requiring the cell to spend energy and use different enzymes to physically bypass them.[cite: 4, 5]

How does compartmentalization prevent glycolysis and gluconeogenesis from canceling each other out?

Glycolysis is strictly cytoplasmic, while gluconeogenesis sequesters its key bypass reactions inside the mitochondria and endoplasmic reticulum.[cite: 4, 5]

Why does the first bypass step of gluconeogenesis (pyruvate to PEP) require two distinct enzymes and two energy molecules (ATP and GTP)?

Reversing the highly exergonic pyruvate kinase step requires massive thermodynamic input, split into a carboxylation followed by a decarboxylation/phosphorylation.[cite: 5]

Mechanistically, what is the role of biotin in pyruvate carboxylase?

It physically carries an activated carbon dioxide molecule and transfers it to the 3-carbon pyruvate to build the 4-carbon oxaloacetate.[cite: 5]

Why is Fructose-1,6-bisphosphatase allosterically inhibited by AMP?

High AMP indicates the cell is starving for energy; it halts gluconeogenesis so the cell doesn't waste its remaining ATP synthesizing glucose.[cite: 5]

Why is Glucose-6-phosphatase (the final step) localized exclusively to the endoplasmic reticulum?

It strips the phosphate off the sugar, allowing the newly formed free glucose to be exported out of the liver to feed other tissues.[cite: 5]

Under what conditions does the cell divert glucose-6-phosphate into the Pentose Phosphate Pathway (PPP)?

When the cell requires reducing power (NADPH) for anabolism or ribose-5-phosphate for nucleic acid synthesis, rather than ATP for energy.[cite: 5]

Conceptually, what happens during the oxidative phase of the PPP?

Glucose-6-phosphate is oxidized twice and oxidatively decarboxylated, extracting 2 NADPH and shedding 1 CO2 to create a 5-carbon sugar.[cite: 5]

Conceptually, what is the purpose of the non-oxidative phase of the PPP?

To physically rearrange leftover 5-carbon sugars back into glycolytic intermediates (fructose-6-phosphate and glyceraldehyde-3-phosphate) so the carbon skeleton isn't wasted.[cite: 5]

Mechanistically, how do transketolases and transaldolases function in the PPP?

They catalyze entirely reversible 2-carbon and 3-carbon group transfers, allowing the pathway to shift carbon blocks seamlessly into or out of glycolysis.[cite: 5]

What happens in the PPP if a cell needs ribose-5-phosphate but DOES NOT need NADPH?

The non-oxidative phase runs completely in reverse, bypassing the oxidative phase and using glycolytic intermediates to build the necessary 5-carbon sugars.[cite: 5]

What is the structural nature of 6-phosphogluconate in the PPP?

It is a phosphorylated ionized acid formed by the very first oxidation of glucose-6-phosphate, acting as the direct precursor for the decarboxylation step.[cite: 5]