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.

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.

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.

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.

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.

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.

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?