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metabolism
sum of all the chemical reactions in a cell
what does metabolism consist of
hundreds of chemical reactions
catabolism
breakdown of nutrients to release energy
anabolism
synthesis of molecules within cells
what do catabolic pathways produce
CO2, H2O, energy
what do pathways transform
substrates into products, via specific intermediates/metabolites
what do enzymes increase
ROR
how do enzymes work
have an active site in which substrate molecules fit
what do the amino acids in the active site of the enzyme protein do
attract the substrate, assist in chemical reactions that convert the substrate to the product, alters the substrate to make the reaction more favourable
What is the most common energy currency molecule in the cell?
ATP
What are the 3 structural components of ATP?
adenine, ribose, 3 phosphate groups
What type of bond joins the phosphate groups in ATP, and why does breaking it release energy?
Phosphoanhydride bonds, high energy bonds which when hydrolysed release free energy that the cell can use to do work
What is ATP hydrolysed into when it releases its energy?
ADP + Pi
What direction of energy transfer occurs when ADP + Pi → ATP?
energy input is required, energetically unfavourable reaction driven by energy from food/sunlight
What direction of energy transfer occurs when ATP → ADP + Pi?
energy is released, made available for cellular work and chemical synthesis
How does ATP drive an otherwise energetically unfavorable reaction (e.g. joining molecule A to molecule B)?
In an "activation step," ATP transfers a phosphate group to one of the reactants (e.g. B–OH → B–P), releasing ADP + Pi; this "activated" high-energy intermediate then undergoes a "condensation step" where it reacts with the other molecule (A) to form the final product (A–B), releasing the phosphate and H2O
In the amino acid activation example (glutamic acid → glutamine), what does ATP do in the "activation step"?
ATP phosphorylates the –OH group of glutamic acid, forming a high-energy phosphorylated intermediate + ADP + Pi
In the amino acid activation example, what happens in the "condensation step"?
Ammonia (NH3) reacts with the high-energy intermediate, displacing the phosphate group (+H2O) to form glutamine (the amide product)
Why do cells need a two-step "activation + condensation" strategy instead of just directly joining two molecules?
Directly joining two stable molecules is often energetically unfavorable; coupling the reaction to ATP hydrolysis (via a high-energy intermediate) makes the overall reaction favorable
What are the two general ways cells make ATP?
Direct ATP synthesis — substrate-level phosphorylation, and Indirect ATP synthesis — via electron carriers and oxidative phosphorylation
Define "substrate-level phosphorylation."
The direct transfer of a high-energy phosphate group from a phosphorylated substrate straight onto ADP, forming ATP — catalysed by an enzyme, no electron transport chain involved
In which two pathways does substrate-level phosphorylation (direct ATP synthesis) occur?
A few steps in glycolysis, and a step in the Krebs (citric acid) cycle
What is the most common electron carrier (coenzyme) used in indirect ATP synthesis?
NAD+
What happens to NAD+ when it accepts electrons and H+ from food breakdown?
It is reduced to NADH
What happens to NADH once it reaches the mitochondria?
oxidised back to NAD+, releasing its electrons and energy, which is used to synthesize ATP
In the "activated carrier molecule" analogy, what does the energetically favorable reaction (food molecule → oxidized food molecule) do?
provides the energy that reduces NAD+ to NADH
what does the energetically unfavorable reaction (molecule available in cell → molecule needed by cell) require?
Energy released when NADH is oxidised back to NAD+
Which process (catabolism or anabolism) reduces NAD+ to NADH, and which uses NADH's energy?
Catabolism reduces NAD+ → NADH, anabolism uses NADH's stored energy
What 3 macronutrient types can be broken down to make acetyl CoA?
glucose (glycolysis), fats (fatty acids), amino acids
What are the 3 stages of nutrient breakdown
1 - breakdown of large macromolecules to simple subunits, 2 - breakdown of simple subunits to acetyl CoA, 3 - complete oxidation of acetyl CoA to CO2 + H2O via the citric acid cycle and oxidative phosphorylation
Which stage of nutrient breakdown produces the LARGE majority of ATP?
stage 3
What are the 3 major stages of glucose breakdown, and where does each occur?
Glycolysis (cytosol) → Krebs/citric acid cycle (mitochondrial matrix) → Electron transport chain & oxidative phosphorylation (inner mitochondrial membrane)
Which of the 3 stages of glucose breakdown use direct (substrate-level) phosphorylation, and which uses indirect (oxidative) phosphorylation?
Glycolysis and the Krebs cycle use substrate-level (direct) phosphorylation; the electron transport chain/oxidative phosphorylation stage uses indirect phosphorylation via ATP synthase
Where in the cell does glycolysis occur?
cytosol
Does glycolysis require oxygen?
no
What is the overall input and output of glycolysis (per 1 glucose)?
Input: 1 glucose + 2 ATP invested. Output: 4 ATP produced (2 ATP net), 2 NADH, 2 pyruvate
What is the NET ATP yield of glycolysis per glucose molecule?
2 ATP (net) because 2 ATP are invested early on and 4 ATP are produced later
What happens to electrons removed during the "step-wise oxidation of sugars" in glycolysis?
They are used to reduce NAD+ to NADH
How is ATP produced directly during glycolysis?
Via substrate-level phosphorylation (direct transfer of a phosphate group from an intermediate to ADP)
What happens to the NADH produced in glycolysis?
It can move into the mitochondria to be used for indirect ATP synthesis (oxidative phosphorylation)
In "How Glycolysis Works," a 6-carbon sugar is split into what, and what molecules are generated per 3-carbon fragment?
Split into two 3-carbon sugar phosphates; each is converted to a 3-carbon pyruvate, generating NADH and ATP along the way
What enzyme complex converts pyruvate into acetyl CoA?
Pyruvate dehydrogenase enzyme complex
Where does the bridge reaction (pyruvate → acetyl CoA) occur?
In the mitochondrial matrix
What are the products from ONE pyruvate entering the bridge reaction?
1x Acetyl CoA + 1x NADH + 1x CO2
Since glycolysis produces 2 pyruvate per glucose, what are the TOTAL products of the bridge reaction per glucose?
2x Acetyl CoA + 2x NADH + 2x CO2
What 2 molecules combine to start the Krebs cycle, and what do they form?
Acetyl CoA (2 carbons) + oxaloacetate (4 carbons) combine to form citrate (6 carbons)
What happens to citrate as it moves around the Krebs cycle?
gradually oxidised
What are the total products of the Krebs cycle from ONE acetyl CoA (i.e., one "turn" of the cycle)?
3 NADH, 1 FADH2, 1 ATP (direct/substrate-level phosphorylation), 2 CO2
What happens to oxaloacetate at the end of one turn of the Krebs cycle?
It is reformed/regenerated, ready to combine with another acetyl CoA and start the cycle again
Approximately how much ATP does each NADH yield when it later passes through oxidative phosphorylation?
~2.5 ATP per NADH
Approximately how much ATP does each FADH2 yield when it later passes through oxidative phosphorylation?
~1.5 ATP per FADH2
Besides ATP production, what other important role do glycolysis and the Krebs cycle play?
provide precursor molecules for biosynthesis of important biological molecules i.e. nucleotides, amino acids
Is glycolysis a linear or cyclic pathway? What about the Krebs cycle?
Glycolysis = linear pathway; Krebs cycle = cyclic pathway
Where does oxidative phosphorylation take place in eukaryotic cells?
The mitochondrial inner membrane
What two molecules drive oxidative phosphorylation (indirect ATP synthesis)
NADH and FADH2
What are the 2 processes that together make up oxidative phosphorylation?
(1) "Oxidative" = the electron transport chain; (2) "Phosphorylation" = ATP synthesis (via ATP synthase)
When NADH is oxidised to NAD+ in the mitochondria, what happens to the released electrons?
They are passed along the electron transport chain — a series of membrane-bound protein complexes/enzymes that accept the electrons (getting reduced) and then pass them on
As electrons move through the electron transport chain, what happens to their energy?
They gradually lose energy, and this released energy is used to pump H+ ions across the inner mitochondrial membrane, from the matrix into the intermembrane space
What does pumping H+ into the intermembrane space create, and why does it matter?
It creates a steep H+ concentration gradient across the inner mitochondrial membrane — this gradient's energy is used to drive ATP synthesis
What happens to electrons at the very end of the electron transport chain?
They combine with O2 (and H+) to form H2O
What are ATP synthases, structurally and functionally?
Large multi-subunit proteins embedded in the inner mitochondrial membrane that act as energy-generating molecular motors
How does ATP synthase convert the H+ gradient into ATP?
It converts the energy from H+ flowing down its concentration gradient into mechanical energy (rotating stalks pushing against stationary head proteins), which is then converted into chemical bond energy — forming a bond between ADP and Pi to make ATP
Roughly how many ATP molecules can ATP synthase produce per second?
About 100 molecules of ATP per second
Roughly how many H+ ions need to move through ATP synthase to produce 1 ATP?
Approximately 4 H+
What are the 2 sets of proteins that make up ATP synthase, and what do they do?
Rotating stalks and stationary heads — the stalks rotate and push against the heads, causing a conformational change in the head subunits that drives ATP formation
Which stage of glucose breakdown uses direct substrate-level phosphorylation to make ATP in the cytosol?
glycolysis
Which stage of glucose breakdown uses direct substrate-level phosphorylation to make ATP in the mitochondrion?
The Krebs cycle
Which stage of glucose breakdown produces ATP via oxidative (indirect) phosphorylation?
The electron transport chain, using ATP synthase, in the inner mitochondrial membrane
What carries electrons from glycolysis into the mitochondrion for oxidative phosphorylation?
NADH
What carries electrons from the Krebs cycle to the electron transport chain?
NADH and FADH2
What happens chemically when ATP is "used" by the cell?
It is broken down (hydrolysed) to ADP + Pi, releasing energy
Name 3 types of cellular work powered by ATP hydrolysis
catalysis, muscle contraction, biosynthesis
What drives most of the body's resting energy expenditure?
Processes powered by ATP hydrolysis
Approximately how much ATP does the human body use/recycle each day?
Roughly its own body weight in ATP each day