Chapter 11: Lipid and Amino Acid Metabolism
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1. (11.1) Beta-oxidation of fatty acids occurs in:
C. β-oxidation is mitochondrial (peroxisomes also do β-oxidation of very-long-chain fatty acids). Fatty acids are first activated to fatty acyl-CoA in the cytoplasm, then shuttled across the inner mitochondrial membrane by carnitine (carnitine palmitoyltransferase I and II).
2. (11.1) Each round of beta-oxidation produces:
B. Four-step cycle: oxidation (→ FADH2), hydration, oxidation (→ NADH), thiolysis (→ acetyl-CoA and a fatty acyl-CoA shorter by 2 C). Palmitate (C16): 7 rounds → 8 acetyl-CoA + 7 NADH + 7 FADH2 ≈ 106 ATP net.
3. (11.2) Fatty acid synthesis differs from beta-oxidation in that it:
D. FA synthesis = cytoplasm + NADPH + malonyl-CoA intermediate + ACC (acetyl-CoA carboxylase, the rate-limiting enzyme) + fatty acid synthase (FAS, a multi-domain enzyme carrying ACP). β-oxidation = mitochondria + NAD+/FAD + direct 2-C cleavage.
4. (11.2) Acetyl-CoA carboxylase (ACC) catalyzes:
A. ACC uses biotin as a cofactor. Activated by citrate (fed-state signal) and insulin (via dephosphorylation). Inhibited by glucagon/epinephrine (via phosphorylation) and by palmitoyl-CoA (product inhibition).
5. (11.3) Malonyl-CoA inhibits:
B. Elegant coordination: when the cell is making fatty acids (high malonyl-CoA), it cannot simultaneously be burning them (CPT-I blocked). One signal switches off the futile cycle.
6. (11.3) Glucagon promotes lipolysis by:
C. Same cAMP-PKA cascade used for glycogen breakdown. PKA phosphorylates HSL (and perilipin on the lipid droplet), enabling triglyceride lipolysis. Free fatty acids are released into blood bound to albumin.
7. (11.4) Ketogenesis occurs primarily in the:
D. Liver is the only organ that makes ketone bodies in significant amounts. When OAA is drained for gluconeogenesis and the TCA cycle can't accommodate all the acetyl-CoA pouring in from β-oxidation, the excess is diverted to ketone bodies (acetoacetate, β-hydroxybutyrate, acetone).
8. (11.4) Paradoxically, the liver cannot use ketone bodies for its own energy because:
A. Liver makes ketones but ships them out for other tissues (brain, muscle, heart) to use. This is a beautiful biochemical division of labor - liver as ketone factory, brain as ketone consumer during fasting.
9. (11.5) During prolonged fasting, the brain adapts to use:
C. Free fatty acids bound to albumin cannot cross the blood-brain barrier, but ketone bodies (small, water-soluble) can. Brain can cover ~60-70% of its energy from ketones after ~3 days of fasting, sparing muscle protein breakdown.
10. (11.5) Ketoacidosis (dangerously low blood pH) occurs when:
B. Acetoacetate and β-hydroxybutyrate are acids (pKa ~3.6 and ~4.7). Huge production during insulin deficiency (DKA) dumps enough H+ into blood to drop pH below 7.35. Classic features: fruity (acetone) breath, Kussmaul breathing, high anion gap.
11. (11.6) The rate-limiting enzyme of cholesterol biosynthesis is:
A. HMG-CoA reductase catalyzes the committed step: HMG-CoA → mevalonate. Statins (atorvastatin, etc.) are competitive inhibitors that resemble HMG-CoA. Lowering liver cholesterol upregulates LDL receptors, lowering blood LDL.
12. (11.6) Cholesterol is the precursor for:
D. Cholesterol's sterane skeleton is the starting material for all steroid hormones (cortisol, aldosterone, testosterone, estradiol, progesterone), bile acids (digestive emulsifiers), and vitamin D (cholecalciferol from 7-dehydrocholesterol + UV).
13. (11.7) Transamination transfers:
C. Aminotransferases (AST, ALT) are the classic examples. PLP (from vitamin B6) shuttles the -NH2. Clinical use: elevated ALT/AST in blood indicates liver damage (enzymes leak out of hepatocytes).
14. (11.7) Oxidative deamination (by glutamate dehydrogenase) produces:
B. Transamination funnels all amino-nitrogen onto α-KG to make glutamate. Glutamate DH then strips it off as NH4+, feeding the urea cycle. The carbon skeleton (α-KG) can return to the TCA cycle.
15. (11.8) The urea cycle occurs in:
A. Liver-only. Urea is shipped to the kidney for excretion. Deficiency of any urea cycle enzyme (e.g., OTC deficiency, the most common) causes hyperammonemia - neurotoxicity from NH4+ accumulation. Presents in neonates or later in life with stress/high protein intake.
16. (11.8) Each urea molecule incorporates two nitrogen atoms, one from ____ and one from ____:
D. N1 enters via NH4+ → carbamoyl phosphate (by CPS-I, with 2 ATP and HCO3-). N2 enters via aspartate (made from glutamate + OAA). The cycle costs 4 high-energy phosphate bonds per urea.
17. (11.9) Glucogenic amino acids:
B. Gluco + genic = "able to make glucose." Most amino acids (18 of 20) are glucogenic - their skeletons can be converted to gluconeogenic precursors. Acetyl-CoA and acetoacetyl-CoA cannot make glucose, so amino acids that only yield these are ketogenic.
18. (11.9) The only two purely ketogenic amino acids are:
C. Leucine and Lysine are exclusively ketogenic. Five others (Ile, Phe, Thr, Trp, Tyr) are both glucogenic and ketogenic. The rest are glucogenic only. Mnemonic: "Lucky Lucy" for Leu/Lys.
19. (11.10) Essential amino acids are:
D. The 9 essentials: Phe, Val, Thr, Trp, Ile, Met, His, Leu, Lys. Mnemonic "PVT TIM HaLL." Non-essentials can be made from other compounds. Conditionally essential amino acids (Arg, Cys, Tyr) become essential in certain conditions (growth, illness).
20. (11.10) A complete protein contains:
A. Animal proteins (meat, eggs, dairy) are usually complete. Most plant proteins are incomplete - missing or low in one or more essential amino acids (e.g., legumes low in Met; grains low in Lys). Combining grains + legumes (rice + beans) gives a complete profile.
21. (11.11) In the starved state, the main fuel for muscle is:
C. Skeletal muscle preferentially uses fatty acids + ketones during fasting, sparing glucose for the brain and RBCs. Muscle glycogen is kept in reserve for sudden exertion. This fuel hierarchy is a major theme across the whole chapter.
22. (11.11) During prolonged starvation, the primary source of blood glucose is:
B. After ~24 h, liver glycogen is gone. Gluconeogenesis takes over. Main substrates: alanine (glucose-alanine cycle from muscle), glycerol (from triglyceride breakdown), lactate (Cori cycle). Fatty acids CANNOT make net glucose (acetyl-CoA can't be converted to pyruvate).
Fats and proteins can be burned for energy, too. This chapter covers how the body breaks down fatty acids (beta-oxidation), builds them back up (fatty acid synthesis), makes ketone bodies during fasting, synthesizes cholesterol, and metabolizes amino acids through transamination and the urea cycle.
Everything Converges on Acetyl-CoA
Here is the simple picture that ties this chapter to Chapters 9 and 10. Every catabolic pathway - whether starting from glucose, fatty acids, or amino acids - is trying to produce acetyl-CoA (or a TCA cycle intermediate). Once acetyl-CoA enters the TCA cycle (citric acid cycle / Krebs cycle), the electrons get stripped off as NADH and FADH2 and delivered to the electron transport chain, where ATP is finally made.
- Fatty acids → beta-oxidation → acetyl-CoA → TCA cycle → NADH/FADH2 → ETC → ATP.
- Amino acids → transamination and deamination → various entry points (pyruvate, acetyl-CoA, or a TCA intermediate) → TCA cycle → NADH/FADH2 → ETC → ATP.
- Ketone bodies → acetyl-CoA (in non-liver tissues) → TCA cycle → NADH/FADH2 → ETC → ATP.
So the pathways in this chapter are mostly about how different fuels get converted into TCA-ready acetyl-CoA. Chapters 9, 10, and 11 really describe one integrated system from different starting materials.
Fat is Long-Term Energy, Protein is Last Resort
Carbs are the first fuel. Fat is the long-term energy depot. Protein is used mainly for building structures, but in extended fasting or starvation, the body will break down muscle to feed gluconeogenesis. The way the body prioritizes these fuels is the central theme of this chapter.
In This Chapter
- 11.1 Beta-Oxidation
- 11.2 Fatty Acid Synthesis
- 11.3 Regulation of Fatty Acid Metabolism
- 11.4 Ketone Body Synthesis
- 11.5 Ketone Body Utilization
- 11.6 Cholesterol Synthesis
- 11.7 Amino Acid Catabolism
- 11.8 The Urea Cycle
- 11.9 Glucogenic vs. Ketogenic Amino Acids
- 11.10 Essential Amino Acids
- 11.11 Metabolic Integration
- Section Test