Heterotrophic Anabolism
A young man who plays soccer in the Liga MX eats tortillas, beans, and chicken, but his muscles don't store corn or chicken protein: they make their own human myosin and glycogen. How does a cell turn molecules from other organisms into its own, and how much does it cost?
Building with what comes from the diet
A heterotrophic cell does not make organic matter from inorganic matter (as a plant does through photosynthesis). It takes nutrients from the diet, breaks them down into small pieces, and uses them to assemble its own biomolecules. Assembling costs energy: that is anabolism.
Think of building a house: the bricks are the amino acids, the labor is the ATP, and the blueprint is the DNA. Without a blueprint, the bricks and the workers are useless.
Define heterotrophic anabolism and give two specific examples of anabolic processes in a human cell (protein synthesis, fatty acid synthesis, or glycogen synthesis),…
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.
To manufacture its proteins, a cell needs amino acids, energy, and information. Explain where a human cell obtains each of these three things from.
Gluconeogenesis: making glucose
Between meals, or during a long fast, the brain still needs glucose. The liver makes it from molecules that are not carbohydrates.
This is related to diabetes, which is very common in Mexico: when insulin fails, or the response to it does, the liver keeps making glucose even though the blood already has plenty.
Synthesis of glycogen and fatty acids
After a meal with lots of tortillas and soda, there is extra glucose. The cell doesn't just let it circulate: it stores it in two ways.
Glycogen
Glycogen is a branched polysaccharide (carbohydrate) made of thousands of glucose units. It is synthesized mainly in the liver and in muscle, from glucose. It is an anabolic process: it consumes energy, because glucose is activated with UTP (forming UDP-glucose) before joining the chain, and that UTP is regenerated at the expense of ATP. It is activated by insulin, after eating.
Fatty acids
If there is still extra energy, the cell converts the excess into fat. Synthesis takes place in the cytosol and follows these steps:
-
Glucose is broken down by glycolysis to pyruvate, which enters the mitochondrion and forms acetyl-CoA.
-
Acetyl-CoA cannot cross the inner mitochondrial membrane. It combines with oxaloacetate and forms citrate, which can leave into the cytosol.
-
In the cytosol, citrate is split and regenerates acetyl-CoA.
-
With that acetyl-CoA, the chain is lengthened two carbons at a time. Each lengthening spends ATP and needs NADPH as reducing power: it supplies the electrons and hydrogen that make the chain more "reduced" (carbons with a lot of hydrogen).
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.
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.
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…
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.
Synthesis of amino acids and proteins
The human body uses 20 amino acids. Some it makes; others it cannot.
Transamination
An amino acid is a carbon skeleton with an amino group. The Krebs cycle produces carbon skeletons: α-ketoglutarate and oxaloacetate are keto acids. In transamination, an amino group passes from an amino acid to a keto acid: the keto acid becomes an amino acid and the original amino acid becomes a keto acid.
-
α-ketoglutarate + amino group → glutamate
-
oxaloacetate + amino group → aspartate
-
pyruvate + amino group → alanine
This is how the nonessential amino acids are made: the cell has the carbon skeleton and can get the amino group from another amino acid.
The essential ones cannot be made in sufficient quantity, because the human body does not have the enzymes to build their carbon skeleton. They must come from the diet.
Assembling the protein
To make a protein, having amino acids is not enough. First they are loaded onto tRNAs (this spends ATP). Then the ribosome joins them following the order set by the mRNA (the information from the DNA); each step forward of the ribosome also spends 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…
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…
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.
The Krebs cycle as an amphibolic pathway
Up to here it seemed that the Krebs cycle only served to burn acetyl-CoA and extract energy. But it is also the parts warehouse from which the carbon skeletons for building come.
Two specific examples:
-
Citrate leaves the mitochondrion for the cytosol, where it releases the acetyl-CoA used to make fatty acids.
-
α-ketoglutarate and oxaloacetate serve as the skeleton for glutamate and aspartate.
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…
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.
- 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.
- 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.
- 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…
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.
- a) Write the reaction catalyzed by pyruvate carboxylase and explain why it is classified as an anaplerotic reaction.
- 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.
- 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.
Growing costs energy
Building biomass is not free: each new bond spends ATP, and many syntheses also use NADPH. That is why a growing teenager needs more energy than an adult of the same weight and activity level.
-
Proteins: each bond between amino acids spends several ATP (tRNA loading and ribosome advance).
-
Membranes: fatty acids and other lipids are synthesized with ATP and NADPH, and every new cell needs new membrane.
-
DNA: every new cell needs to copy its DNA, which requires nucleotides and ATP.
And the precursors and ATP always come from catabolism: from the glucose and fats of the diet, which are oxidized in cellular respiration. More anabolism demands more catabolism.
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…
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.
- a) Interpret the nitrogen balance of both individuals and deduce which families of biomolecules are being synthesized and net accumulated in the adolescent.
- 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.
- 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.
Go back to the beginning: the soccer player's cells break down the chicken protein and the tortilla starch into small pieces, and with ATP, NADPH, and the information in their DNA they assemble their own myosin and glycogen.