Metabolic Reactions

What is glycolytic flux?

Glycolytic flux refers to the rate at which glucose is metabolized through glycolysis to produce pyruvate, ATP, and NADH.

What is phosphoenolpyruvate (PEP), and what is its role in metabolism?

Phosphoenolpyruvate (PEP) is a high-energy intermediate in glycolysis.

• It is the second-to-last compound in the glycolytic pathway.

• It donates a phosphate group to ADP to form ATP and pyruvate in a reaction catalyzed by pyruvate kinase.

🧪 Reaction:

PEP + ADP→ Pyruvate + ATP

What is α-ketoglutarate, and what is its role in the citric acid cycle? ("I Keep Succinate Around")

α-Ketoglutarate is an important intermediate in the citric acid cycle.
— for Isocitrate → Ketoglutarate → Succinyl-CoA → ...

How many ATP are produced per mole of glucose under anaerobic conditions, and why?

NAD⁺ is regenerated via fermentation (e.g., lactate or ethanol production), allowing glycolysis to continue

Glucose → 2 Pyruvate → 2 Lactate + 2 ATP

What is glycolysis, and what are its key features?

Glycolysis is the metabolic pathway that breaks down glucose (6C) into 2 pyruvate (3C) molecules, producing ATP and NADH.

Where does glycolysis happen?

"Glucose gets sliced in the cytoplasm/cytosol!"

Is glycolysis an aerobic or anaerobic process?

The fate of pyruvate depends on oxygen availability:

• Aerobic: → Acetyl-CoA → TCA cycle

• Anaerobic: → Lactate (in animals) or ethanol (in yeast)

What do reductase enzymes do?

Reductases are enzymes that catalyze reduction reactions, which involve the gain of electrons (or hydrogen atoms) by a molecule.

What is β-oxidation and what is its purpose?

β-Oxidation is the metabolic process by which fatty acids are broken down in the mitochondrial matrix to produce acetyl-CoA.

What is gluconeogenesis?

Gluconeogenesis is the metabolic pathway that synthesizes glucose from non-carbohydrate sources, such as:

• Lactate

• Amino acids (e.g., alanine)

• Glycerol

What is the main function of insulin in metabolism?

“Insulin = In Storage”
(Helps store nutrients: glucose → glycogen, fat storage, etc.)

How are oxidation and reduction defined in terms of oxidation state?

• Reduction = Decrease in oxidation state (gain of electrons)

• Oxidation = Increase in oxidation state (loss of electrons)

What is hyperglycemia?

Hyperglycemia is a condition where blood glucose levels are abnormally high.

What is lactic acid fermentation?

Lactic acid fermentation is an anaerobic process where pyruvate is reduced to lactate, regenerating NAD⁺ to keep glycolysis running.

🧬 Reaction:
Pyruvate + NADH → Lactate + NAD⁺

What are free radicals and why are they reactive?

Free radicals are atoms or molecules that have one unpaired valence electron, making them highly reactive.

How can inborn errors of metabolism be treated when a metabolic step is blocked?

“Replace or Reroute”
Replace the enzyme, or reroute the metabolism through an independent path.

What are inborn errors of metabolism?

Inborn errors of metabolism (IEMs) are genetic disorders caused by mutations in genes that encode enzymes, leading to defects in metabolic pathways.

What is oxidative phosphorylation, and how does it produce ATP?

the final stage of aerobic cellular respiration, where ATP is synthesized using energy from electrons transferred through the electron transport chain (ETC) and a proton gradient.

Where is the electron transport chain?

inner mitochondrial membrane

key componets of oxidative phosphorylation:

1. Electron transport chain

2. Chemiomosis

3. Oxygen

what happens in the electron transport chain?

• Electrons from NADH and FADH₂ pass through complexes I–IV

• Energy released pumps H⁺ ions into the intermembrane space

what happens during chemiomosis?

• H⁺ ions flow back through ATP synthase

• This flow drives the phosphorylation of ADP → ATP

what role does oxygen play in oxidative phosphorylation?

• Oxygen acts as the final electron acceptor, forming water

• Essential for maintaining electron flow and ATP production

How many electrons does NADH carry, and what is its role?

"NADH = 2 tickets to the ETC"

Each NADH delivers 2 electrons to the electron transport chain.

What is Cytochrome c and what is its role in cellular respiration?

Transfers 1 electron at a time from Complex III (cytochrome bc₁ complex) to Complex IV (cytochrome c oxidase).

What is the Pentose Phosphate Pathway (PPP) and what are its main functions?

• The Pentose Phosphate Pathway (PPP) is an alternative pathway to glycolysis that occurs in the cytoplasm.

• It does NOT produce ATP directly.

• Produces NADPH and Ribose-5-phosphate

Which two enzymes in the Pentose Phosphate Pathway (PPP) catalyze the production of NADPH?

Enzymes that produce NADPH in PPP (Oxidative Phase):

1. Glucose-6-phosphate dehydrogenase (G6PD):

2. 6-Phosphogluconate dehydrogenase:

they are oxidoreductases

Is ATP hydrolyis exothermic or endothermic?

exothermic because some of the energy is released as thermal energy (heat), which helps maintain body temperature.

ATP Hydrolysis

ATP Hydrolysis:

• ATP (adenosine triphosphate) + H₂O → ADP (adenosine diphosphate) + Pi (inorganic phosphate) + energy

How are the Citric Acid Cycle and Electron Transport Chain interconnected?

"CAC fuels the ETC train."

The Citric Acid Cycle fuels the Electron Transport Chain with electron carriers.

• The Citric Acid Cycle (CAC) oxidizes acetyl-CoA to produce NADH and FADH₂, which carry high-energy electrons.

• These electron carriers feed electrons into the Electron Transport Chain (ETC) in the mitochondrial inner membrane.

What is Succinate Dehydrogenase?

• In the CAC, it oxidizes succinate, reducing FAD to FADH₂.

• In the ETC, FADH₂ donates electrons directly to the chain via Complex II.

What happens when the Electron Transport Chain (ETC) is decoupled from ATP synthesis?

• Normally, the ETC creates a proton gradient across the inner mitochondrial membrane that drives ATP synthesis via ATP synthase.

• Decoupling occurs when protons leak back into the mitochondrial matrix without passing through ATP synthase.

What is decoupling?

• Effects of Decoupling:

  1. Increased oxygen consumption

     • The ETC keeps running rapidly to restore the proton gradient, using up more oxygen.

  2. Decreased ATP synthesis

     • Proton gradient is dissipated without making ATP (uncoupling bypasses ATP synthase).

Carbohydrate Metabolism

• Glycolysis: Glucose → Pyruvate (cytoplasm); yields ATP & NADH.

• Gluconeogenesis: Formation of glucose (mainly liver).

• Glycogenesis: Storage of glucose as glycogen.

• Glycogenolysis: Breakdown of glycogen to glucose.

Aerobic Respiration (Energy Production)

• Pyruvate Oxidation: Pyruvate → Acetyl-CoA (mitochondria).

• Citric Acid Cycle (TCA/Krebs): Acetyl-CoA → CO₂ + NADH/FADH₂.

• Electron Transport Chain (ETC) & Oxidative Phosphorylation: NADH/FADH₂ → ATP.

Lipid Metabolism

• Beta-Oxidation: Fatty acids → Acetyl-CoA.

• Lipogenesis: Fatty acid synthesis (from Acetyl-CoA).

• Ketogenesis: Ketone body formation (fasting/starvation).

Protein/Amino Acid Metabolism

• Deamination: Removal of amino group → Urea cycle (excretion).

• Transamination: Amino acid interconversion.

• Glucogenic & Ketogenic Amino Acids: Fuel for gluconeogenesis or ketogenesis.

Other Key Pathways:

• Pentose Phosphate Pathway (PPP): NADPH + Ribose-5-phosphate (DNA/RNA synthesis).

• Fermentation (Anaerobic): Pyruvate → Lactate (low O₂).

Major metabolic pathway catergories:

5

1. Carbohydrate Metabolism

2. Aerobic Respiration (Energy Production)

3. Lipid Metabolism

4. Protein/Amino Acid Metabolism

5. Other Key Pathways

How are reactive oxygen species (ROS) formed?

During Cellular Respiration (ETC leakage):

• In the electron transport chain (ETC), electrons can "leak" from Complexes I and III and react with oxygen (O₂), forming:

  • Superoxide anion (O₂•⁻)

How do reactive oxygen species (ROS) cause oxidative stress and lead to cytochrome c release?

ROS tear the mitochondria → cytochrome c escapes → apoptosis begins.

Oxidative stress

"Too many sparks, not enough shields."

• ROS are sparks, antioxidants are shields. Without balance → damage!

What is DNA Renaturation (DNA Reannealing)?

the process where single-stranded DNA (ssDNA) reforms a double-stranded DNA (dsDNA) helix after being separated (denatured).

What happens to energy during DNA renaturation, and what stabilizes the reformed double helix?

During DNA renaturation:

• Complementary strands reanneal (reform hydrogen bonds).

• Energy is released (exothermic) as hydrogen bonds and base stacking interactions stabilize the DNA.

cellulose and human digestion

Cellulose is a polysaccharide that humans cannot digest because we lack necessary enyzmes

butyrate metabolism

Butyrate metabolism refers to how the short-chain fatty acid butyrate (C4) is produced and utilized in the body, especially in the colon and liver.

Metabolized in mitochondria via:

• β-oxidation → Acetyl-CoA → TCA cycle → ATP production

Fatty Acids (FAs):

Fatty acids are carboxylic acids with long hydrocarbon chains. They are fundamental building blocks of lipids