Energy Metabolism and Catabolism

ATP: The Universal Energy Currency

• ATP formula: $ATP + H_2O \rightarrow ADP + P_i + 7.4\,kcal/mol$.
• $P_i$ represents phosphate ions: $H_2PO_4^-$ and $HPO_4^{2-}$.
• Energy ranking (high to low):
      - Pyrophosphates ($-7.8\,kcal/mol$).
      - ATP ($-7.5\,kcal/mol$).
      - Sugar phosphates (e.g., glucose 6-phosphate: $-3.3\,kcal/mol$).

Overview of Metabolism

• Metabolism: All chemical processes in living beings.
• Catabolism: Breakdown of large molecules to small ones; releases energy.
• Anabolism: Creation of large molecules from small ones; consumes energy.
• Stage I of Catabolism: Digestion through hydrolysis; no ATP is produced.
• Stage II of Catabolism: Breakdown to create ATP and high-energy molecules like Acetyl-CoA.
• Stage III of Catabolism: Citric Acid Cycle and electron transport; occurs in aerobic conditions.

Stage I: Digestion

• Carbohydrates: Polysaccharides are broken into monosaccharides (glucose, galactose, fructose) via salivary and pancreatic $\alpha$-amylase.
• Proteins: Denatured by HCl and pepsin in the stomach; hydrolyzed by chymotrypsin, trypsin, and various peptidases in the small intestine.
• Lipids: Emulsified by bile salts; hydrolyzed by pancreatic lipase into mono- and diglycerides.
• Zymogens: Inactive enzyme precursors activated by cleaving the peptide chain.

The Citric Acid Cycle (Stage III)

• Location: Mitochondria.
• Synonyms: Krebs Cycle, Szent-Györgyi-Krebs Cycle, Tricarboxylic Acid Cycle.
• Net Reaction: $Acetyl-CoA + 3NAD^+ + FAD + GDP + P_i \rightarrow 2CO_2 + CoA + 3NADH + FADH_2 + GTP$.
• Key intermediates: Citrate ($6\,carbons$), Isocitrate, $\alpha$-ketoglutarate, Succinate, Fumarate, Malate, and Oxaloacetate ($4\,carbons$).

Electron Transport and Oxidative Phosphorylation

• Takes place in the mitochondria; requires oxygen as the final electron acceptor to form $H_2O$.
• Energy yield:
      - $10\,H^+$ pumped per NADH; creates $2.5\,ATP$.
      - $6\,H^+$ pumped per $FADH_2$; creates $1.5\,ATP$.
      - $4\,H^+$ are required to synthesize $1\,ATP$.

Carbohydrate Catabolism

• Glycolysis: Processes glucose into two pyruvates ($3\,carbons$ each).
      - Equation: $Glucose + 2ATP + 2NAD^+ \rightarrow 2\,pyruvate + 4ATP + 2NADH$.
      - Net gain: $2\,ATP$.
• Gluconeogenesis: Synthesis of glucose during starvation; requires $6\,ATP$.
• Feedback control: Regulated at Steps 1, 3 (main control), and 10.
• Fate of Pyruvate:
      - Aerobic: Becomes Acetyl-CoA.
      - Anaerobic (vertebrates): Becomes Lactate.
      - Anaerobic (microorganisms): Becomes Ethanol.

Lipid and Protein Catabolism

• $\beta$-oxidation: Spiral pathway removing two carbons per cycle to produce Acetyl-CoA, $FADH_2$, and NADH.
• Transamination: Amine group ($-NH_3$) is transferred to $\alpha$-ketoglutarate to form glutamate.
• Oxidative Deamination: Amine group is removed from glutamate as $NH_4^+$ and enters the Urea Cycle.
• Urea: Final product of the amine group excretion ($NH_2-C(=O)-NH_2$).

Questions & Discussion

• Mistakes are never made during DNA replication: False.
• Which mutation is least likely to have a large effect on amino acids: Substitution.
• Type of virus that converts RNA to DNA when infecting: Retrovirus.
• Based on provided data, would hydrolysis of ADP to AMP + Pi provide enough energy to synthesize glucose 1-phosphate from glucose: Yes.
• Breakdown of large molecules to produce energy: Catabolism.
• Reaction type in Stage I: Hydrolysis.
• Essential compound from Stage II for CAC or synthesis: Acetyl-CoA.
• Reaction in CAC Step 2: Isomerization producing a secondary alcohol.
• Outcome of NADH production: NAD+ is reduced.
• Net yield of ATP from complete oxidation of 1 Mol Acetyl-CoA: $10\,ATP$.
• Net yield of ATP from complete oxidation of 1 Mol Glucose: $36\text{ to } 38\,ATP$.