The catabolism of lipids and proteins

Explain what β-oxidation is, where in the cell it occurs, and what product it feeds into the Krebs cycle. State also which electron-carrier molecules are generated during the process.

In β-oxidation, fatty acids are shortened by two carbon atoms at a time. Explain why it receives that name (on which carbon of the chain the oxidation occurs) and what fragment is released in each round of the process.

A saturated fatty acid with $18$ carbon atoms is completely degraded by β-oxidation. Calculate how many rounds of β-oxidation are needed and how many acetyl-CoA molecules are obtained, reasoning the calculation.

Where are reserve fats stored in the organism? Explain what happens in adipose tissue when the body needs energy (lipolysis) and which molecules are then released into the blood.

Reason why 1 g of fat yields more ATP than 1 g of glucose, referring to the degree of reduction of the carbons in the hydrocarbon chain of fatty acids and the quantity of electrons they can donate to the respiratory chain.

During prolonged fasting or a diet very high in fat, ketone bodies in the blood increase. Explain what ketone bodies are and reason why they appear when the Krebs cycle cannot assimilate all the acetyl-CoA coming from β-oxidation.

Dietary proteins are not stored in the body. Explain what happens to excess amino acids: which group is removed, how the excess nitrogen is eliminated, and what the fate of the rest of the molecule is.

Urea is formed in the liver from ammonium. Explain why the organism invests energy in converting ammonium, which is very toxic, into urea, and state how the latter is eliminated from the body.

Describe the deamination of amino acids and explain the fate of the two resulting parts: the amino group (and its conversion to urea) and the carbon skeleton (which can enter catabolic pathways as pyruvate, acetyl-CoA, or Krebs cycle intermediates).

The diagram summarizes how the catabolic pathways of carbohydrates, lipids, and proteins converge in aerobic cellular catabolism:

1. a) Identify the catabolic processes indicated by ?1 and ?2. If a drug selectively inhibits the mitochondrial carnitine shuttle, deduce which pathway (?1, ?2, or glycolysis) will be blocked and which substrates the cell will need to prioritize to maintain acetyl-CoA levels.
2. b) During prolonged fasting, a large portion of the Krebs cycle oxaloacetate is diverted to hepatic gluconeogenesis while pathway ?1 is hyperactivated. Justify what alternative fate the accumulated acetyl-CoA will follow, given that it cannot condense into the Krebs cycle.
3. c) If rotenone (an inhibitor that blocks electron transfer from NADH to complex I of the respiratory chain) is added, predict how the intramitochondrial ratio $[\text{NADH}]/[\text{NAD}^+]$ will change and what direct consequence this will have on the rate of the Krebs cycle.

Palmitic acid ($\text{C}_{16}\text{H}_{32}\text{O}_2$) yields about $106\ \text{ATP}$ upon complete oxidation with a consumption of $23\ \text{moles of }\text{O}_2$. In turn, glucose ($\text{C}_6\text{H}_{12}\text{O}_6$) generates about $36\ \text{ATP}$ consuming $6\ \text{moles of }\text{O}_2$.

1. a) Calculate the energy yield per carbon atom ($\text{ATP}/\text{C}$) of both substrates and biochemically justify the reason for this difference by analyzing the average oxidation state of carbon in carbohydrates and lipids.
2. b) Glycogen is stored in a hydrated form (retaining approximately $2\ \text{g}$ of water per gram of dry glycogen), whereas triglycerides accumulate in an anhydrous form. Knowing that $1\ \text{g}$ of pure fat provides about $9\ \text{kcal}$ and $1\ \text{g}$ of dry glycogen provides $4\ \text{kcal}$, calculate the total weight that a migratory bird would have to accumulate to have a reserve of $18.000\ \text{kcal}$ if stored as triglycerides versus hydrated glycogen, and deduce the adaptive advantage this represents.
3. c) During intense muscular exertion in which the $\text{O}_2$ supply becomes limiting, calculate which substrate yields more ATP molecules per mole of $\text{O}_2$ consumed ($\text{ATP}/\text{O}_2$) and predict which one the muscle will prioritize in that situation.

The blood and urinary parameters of a volunteer are analyzed during a four-week hunger strike. In the first $24$ hours, hepatic glycogen is completely depleted; however, blood glucose remains stable at around $60\text{ mg/dL}$. Plasma levels of acetoacetate and $\beta$-hydroxybutyrate increase by more than $25$-fold starting on day four, whereas urinary urea excretion shows an initial peak on days 2–3 and then drops to stable minimum values.

1. a) Justify where plasma glucose comes from starting on the second day if glycogen is no longer available, and explain why the net breakdown of muscle proteins (reflected in urea) decreases so markedly after the first week.
2. b) Explain why the brain cannot directly oxidize fatty acids derived from adipose tissue and how the synthesis of ketone bodies acts as a protective mechanism for skeletal muscle mass.
3. c) If this individual were accidentally administered a high dose of insulin on day 15 of fasting, predict and justify what would happen to lipolysis in adipocytes, to ketone body production, and to the energy supply to the brain.