Exercises: Heterotrophic anabolism

Define heterotrophic anabolism and give two specific examples of anabolic processes in a human cell (protein synthesis, fatty acid synthesis, or glycogen synthesis), stating what these processes consume (ATP, NADPH, and precursors).

To manufacture its proteins, a cell needs amino acids, energy, and information. Explain where a human cell obtains each of these three things from.

Explain what glycogen is, in which organs it is mainly synthesised, and from which precursor it is formed, stating whether the process consumes or releases energy.

Transamination allows cells to manufacture non-essential amino acids. Explain what this reaction consists of and how Krebs cycle intermediates (such as α-ketoglutarate or oxaloacetate) serve as a starting point to synthesise amino acids.

Reason why essential amino acids must be supplied through the diet while non-essential ones do not need to be, and explain what metabolic problem arises when a diet is deficient in complete proteins.

When there is an excess of glucose, the cell synthesises fatty acids in the cytosol from acetyl-CoA. Explain where this acetyl-CoA comes from, how it reaches the cytosol, and what role NADPH plays in this synthesis.

In a culture of hepatocytes subjected to a high-calorie diet rich in carbohydrates, intense cytosolic synthesis of fatty acids is observed along with, in a coordinated manner, the synthesis of non-essential amino acids. The diagram shows the Krebs cycle functioning as the central metabolic hub.

1. a) Reasonably deduce the identity of intermediate ?1 leaving the mitochondrion and explain what membrane permeability problem its exit solves to enable fatty acid synthesis in the cytosol.
2. b) Identify intermediates ?2 and ?3, precursors of glutamate and aspartate (or oxaloacetate for gluconeogenesis), and justify why the continuous removal of these molecules would stop the oxidation of acetyl-CoA if "anaplerotic reactions" did not intervene.
3. c) Based on the above, justify why describing the Krebs cycle as a purely catabolic pathway is a biological error.

A newborn with a congenital metabolic disease presents with fasting hypoglycemia, severe lactic acidosis, and an elevated plasma alanine concentration. Enzymatic assays show a complete deficiency of mitochondrial pyruvate carboxylase, whereas the pyruvate dehydrogenase complex shows normal activity.

1. a) Write the reaction catalyzed by pyruvate carboxylase and explain why it is classified as an anaplerotic reaction.
2. b) Justify why the deficiency of this enzyme blocks both gluconeogenesis from pyruvate and the ability of mitochondria to oxidize acetyl-CoA derived from the $\beta$-oxidation of fatty acids.
3. c) Predict what will happen to the cellular concentration of acetyl-CoA and explain the biochemical cause behind this patient's accumulation of pathological amounts of lactic acid in the blood.

A 15-year-old adolescent in the middle of a growth spurt and a 35-year-old sedentary adult have the exact same body mass ($62\ \text{kg}$). However, physiological analyses show that the adolescent has a markedly positive net nitrogen balance (+3.8 g N/day) compared to the adult's zero balance, and their recommended daily energy intake is about $600\ \text{kcal}$ higher than the adult's.

1. a) Interpret the nitrogen balance of both individuals and deduce which families of biomolecules are being synthesized and net accumulated in the adolescent.
2. b) Justify in thermodynamic terms (enthalpy and entropy) why the polymerization of monomers to form muscle mass and cell membranes requires a continuous input of metabolic energy, explaining how coupling with ATP hydrolysis is involved.
3. c) If the adolescent were to maintain a restricted caloric intake identical to that of the adult, reasonably predict the impact on their bone and muscle growth, justifying the metabolic origin of the carbon precursors and reducing power required for anabolism.