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.

What is gluconeogenesis and in which organ does it mainly occur? Give two examples of non-carbohydrate precursors from which the organism can make glucose.

Protein synthesis is one of the processes that consume the most energy in the cell. State in which steps of the synthesis energy is spent (activation of the amino acids, translation) and explain why a cell that makes many proteins needs to respire intensely.

During digestion, nutrients are broken down into small molecules and anabolism does the opposite. Give two examples of polymers that the human organism makes from monomers coming from the diet and state which is the monomer of each one.

Muscle proteins are degraded and resynthesised constantly even though the muscle does not grow. Explain what this protein turnover consists of and what implication it has for energy expenditure at rest.

What role does the liver play in anabolism? Name two synthesis processes it carries out (glycogen, plasma proteins, cholesterol, fatty acids) and explain one of them briefly.

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.

Gluconeogenesis uses almost all the enzymes of glycolysis in the reverse direction, but bypasses three irreversible steps with different reactions. Explain why the cell prevents glycolysis and gluconeogenesis from running at the same time (futile cycles) and how both pathways are coordinated through the hormones insulin and glucagon.

After a carbohydrate-rich meal, insulin secretion increases. Explain what anabolic processes insulin activates in the liver, in muscle and in adipose tissue, and what happens to those same processes during the period between meals.

Cholesterol is synthesised in the organism from acetyl-CoA, although it is also obtained from the diet. Explain why the organism regulates its own cholesterol synthesis according to the dietary supply and give two examples of essential molecules made from it.

A person loses $5\ \text{kg}$ of body fat after months of diet and exercise. Reason what has metabolically happened to that adipose tissue (lipolysis and oxidation of the fatty acids) and explain why most of the lost carbon leaves the body as exhaled $\text{CO}_2$.

Muscle stores glycogen but cannot release glucose into the blood, because it lacks the enzyme glucose-6-phosphatase. Explain what it uses its glycogen for, then, why the liver can indeed pour glucose into the blood and what advantage this division of labour has for the organism as a whole.

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.

During a $400\ \text{m}$ sprint event, skeletal muscle fibers function under almost completely anaerobic conditions. Upon crossing the finish line, the athlete stops, but their oxygen consumption remains much higher than at rest for more than 20 minutes (the "oxygen debt" phenomenon or EPOC).

1. a) Justify why muscle cells need to convert pyruvate into lactate rather than stopping glycolysis, specifying which limiting coenzyme is recycled in this reaction.
2. b) Lactate is released into the bloodstream and participates in the Cori cycle. Calculate the net ATP balance for the organism for each glucose molecule fermented in the muscle and resynthesized in the liver, and justify why this cycle represents a net energy cost to the organism.
3. c) Relate the net balance obtained in section b to the high hepatic oxygen consumption after the race: which hepatic mitochondrial process consumes that extra $\text{O}_2$ and for what metabolic purpose?

In a study on prolonged fasting, the metabolic parameters of a volunteer subject are monitored for 25 days. The following phases are observed:

1. Blood glucose decreases slightly during the first 36 hours and then remains stable at around $3.8\ \text{mmol/L}$.

2. Urinary nitrogen (urea) excretion reaches a peak around day 3 (about $13\ \text{g/day}$), but drops to one third by day 10 ($4\ \text{g/day}$) and stabilizes.

3. The plasma concentration of acetoacetate and $\beta$-hydroxybutyrate increases by more than 25-fold over the first two weeks.

1. a) Justify the urea excretion peak on day 3: which macromolecules are being preferentially degraded, in which tissue does this occur, and which hepatic metabolic pathway fuels this catabolism?
2. b) Interpret the drastic reduction in urea excretion from day 10 onwards: relate this fact to the increase in ketone bodies and explain what metabolic change in the brain allows the organism's muscle mass to be preserved.
3. c) A student proposes that, to avoid losing muscle, the liver could directly convert fatty acids derived from adipose tissue into glucose via gluconeogenesis. Reasonably refute their proposal based on the stoichiometry of decarboxylation in the Krebs cycle.

A lactating mother secretes about $750\ \text{mL}$ of breast milk daily, which amounts to transferring approximately $500\ \text{kcal/day}$ to her infant in the form of chemical nutrients: carbohydrates (lactose: $7.0\,\%$), lipids (triglycerides: $4.0\,\%$), and proteins (casein and lactalbumin: $1.0\,\%$). However, nutrition committees estimate that her basal and functional caloric expenditure increases by about $650\ \text{kcal/day}$.

1. a) Apply the laws of thermodynamics to cellular metabolism to justify why the energy the mother must ingest ($650\ \text{kcal}$) is noticeably higher than the chemical energy contained in the milk she produces ($500\ \text{kcal}$).
2. b) Analyze at the biochemical level the energy cost required to assemble the components of milk: indicate which nucleoside triphosphates or reducing equivalents are specifically consumed in the activation of monosaccharides to form the O-glycosidic bond of lactose and in the condensation of amino acids to form peptide bonds.
3. c) If the mother follows a diet with a severe caloric and carbohydrate deficit, predict which body tissues will mobilize reserves to sustain lactogenesis and justify which catabolic pathways will be activated as a priority in them.

In an agronomic trial, the symbiosis between Rhizobium and soybean plants (Glycine max) is analyzed. Three conditions are studied: Batch A grows in nitrogen-poor soil; Batch B receives continuous inorganic nitrogen fertilizer; and Batch C is a mutant soybean line lacking the functional leghemoglobin gene, inoculated with a normal Rhizobium strain.

1. a) In Batch A, the bacteroids consume up to 20 % of the carbohydrates produced by the plant to sustain nitrogenase activity. Justify at the molecular level why the reduction of $\text{N}_2$ to $\text{NH}_4^+$ requires such a high expenditure of ATP and reducing power (take into account the type of bond in dinitrogen) and what net metabolic benefit the plant obtains in exchange for giving up those carbohydrates.
2. b) In Batch B, the plant drastically reduces nodule formation and represses bacterial nitrogenase activity. Justify the bioenergetic logic of this adaptive response.
3. c) In Batch C, biological nitrogen fixation drops to zero even though the nitrogenase enzyme is structurally intact. Explain the cause of this failure and reasonably predict which essential macromolecules will see their synthesis interrupted in the plant.

A healthy individual undergoes a clinical trial of controlled fasting for 48 hours after having consumed a balanced diet. Blood levels of glucose, free fatty acids, ketone bodies, insulin, and glucagon are periodically monitored.

1. a) During the first 12 hours, blood glucose remains virtually constant without food intake. Justify which hepatic pathway is primarily responsible for sustaining blood glucose in this first phase and how the glucagon/insulin ratio regulates the activation of this pathway compared to its antagonistic pathway.
2. b) At 36 hours of fasting, liver glycogen is completely depleted; however, blood glucose does not drop to zero, and the concentration of ketone bodies in the blood increases very markedly. Explain what non-carbohydrate substrates the liver uses to synthesize glucose de novo and why the massive degradation of fatty acids in hepatocytes necessarily leads to ketogenesis at this stage.
3. c) If this individual had an inactivating mutation in hepatic carnitine palmitoyltransferase I (CPT-I), reasonably predict what would happen to their plasma glucose and ketone body levels after 24 hours of fasting.