UNIT 6 - Metabolism I Flashcards
For metabolism in multicellular organisms to proceed efficiently, it is important that the final products be gases, water, or both. Why?
Avoid waste build up - make universal solvent, gas or both.
To maintain a steady state of metabolism, there must be no possibility of build up. This means that the end result must be the organism’s universal solvent, gasses, or a combination of the two.
Look at the two starred reactions in the lesson just covered (the redox reactions involving NADH and O2). Compare the tendency of NADH to donate electrons and the tendency of oxygen to accept them. If NADH and oxygen are mixed, will the electrons stay with NADH or go to oxygen? Explain.
If NADH and oxygen are mixed, electrons will be transferred from NADH to oxygen with the release of considerable energy
What structural feature do the “high‑energy” compounds ATP, FADH2, and NADH share with acetyl‑CoA?
The “high energy” compounds share and ADP unit, or in acetyl-CoA’s case a closely related derivative
What is the overall ΔG for glycolysis? Why can the reaction never come to equilibrium in vivo?
Large enough negative delta G that as long as Glucose is added, pyruvate will continue to be made.
The “Pasteur effect” is the dramatic decrease in glucose consumption when oxygen is introduced to an anaerobic fermentation broth. Why do the yeast cells use less glucose after oxygen is introduced? How much less glucose do they use after oxygen is introduced?
The introduction of oxygen allows yeast to convert from anaerobic to aerobic metabolism. Since aerobic metabolism provides more ATP, the amount of glucose that must be used to nourish the yeast is much less. Approximately 6% of the glucose metabolized anaerobically is needed to provide the same amount of energy under aerobic conditions.
Why do you get hot when you exercise?
PEP has a hugely negative delta G so what is not used is converted to heat.
PEP is a very high‑energy compound. The reaction that converts PEP to pyruvate is so highly energetically favourable (very negative ΔG) that there is almost enough energy in PEP to stimulate production of a second ATP through substrate level phosphorylation, but it is not used. The excess energy is lost as heat.
What are the three enzymes that are regulated in glycolysis? How does AMP affect glycolysis?
Hexokinase, PFK, and pyruvate kinase (1, 3, 10)
The three enzymes that are regulated in glycolysis are: hexokinase, phosphofructokinase (PFK), and pyruvate kinase. High amounts of AMP activate PFK and pyruvate kinase, which stimulate glycolysis because ATP is needed.
List the possible uses of pyruvate.
ATP production and NAD+ regeneration through Kreb’s cycle and electron transport
glucose synthesis by gluconeogenesis
ATP production and NAD+ generation and lactate or ethanol production by fermentation
alanine synthesis
oxaloacetate synthesis
What does the liver do with the lactate that is produced during heavy exercise?
The liver converts the lactate to pyruvate in the Cori Cycle. The enzyme lactate dehydrogenase catalyzes this conversion. The pyruvate is then used to make glucose by gluconeogenesis in the liver, and can go back into the blood to be taken up by muscles and used for energy.
Can one get a net synthesis of oxaloacetate if one adds acetyl‑CoA to a system that contains only the enzymes and intermediates of the citric acid cycle? (Consider one complete cycle.)
No, one cannot get a net synthesis of oxaloacetate in these circumstances. Acetyl‑CoA is a 2‑carbon species and two molecules of CO2 are given off for each turn of the cycle. Therefore no net synthesis is possible. In fact, this is the point of the citric acid cycle. All the atoms of glucose are discarded and the glucose energy is conserved in one molecule of GTP and in high‑energy electrons.
What is the purpose of the production of NADH and FADH2 in the citric acid cycle (CAC or TCA)?
They are used to drive the ETC and produce ATP
In general, how is the CAC connected to many other metabolic pathways? What compound acts as the link to these pathways?
Acetyl-CoA links glycolysis, fatty-acid oxidation, and amino acids break down to the CAC.
Acetyl‑CoA is central in linking glycolysis with the citric acid cycle, but many other metabolic pathways can be fed through the CAC and on to electron transport for energy production. Fatty acids and amino acids, as well as carbohydrates, can be metabolized to acetyl‑CoA. The bulk of the ATP molecules that result from “metabolism” come from the processing of acetyl‑CoA through the citric acid cycle, and then into the electron transport chain.
What two enzymes are present in the glyoxylate cycle that animals lack?
Isocitrate lyase and
malate synthase.
Compare the overall outcomes of the CAC and the glyoxylate cycles.
CAC produces 1 oxaloacetate per turn of the cycle (there is no net production of oxaloacetate in the CAC) and
the glyoxylate cycle produces 2.
The extra one produced by the glyoxylate cycle in plants and bacteria means that, unlike animals, these organisms can use the oxaloacetate to make glucose and other molecules
Plants and bacteria can turn acetyl‑CoA into glucose, while animals cannot.
plants and bacteria can turn acetyl‑CoA from fat into glucose but animals cannot.
advantage of the CAC in animals, though, is the higher production of NADH and FADH2. One turn of the glyoxylate cycle produces 1 NADH and 1 FADH2, whereas one turn of the CAC results in 3 NADH, 1 FADH2, and 1 GTP. This makes sense considering the high energy requirements of animals.
Why is the glyoxylate cycle important for plants, fungi, protists, and bacteria?
Why would the CAC be more important for animals?
The higher energy output of the CAC for animals provides the requirements for the production of higher amounts of ATP through the electron transport chain, which is needed for the mobility of animals.
The extra oxaloacetate produced through the glyoxylate cycle in plants, bacteria, and protists is necessary to produce carbohydrate for structure and storage, which are necessary functions for these organisms.
Why is acetyl‑CoA such an important molecule? Name three pathways that require this molecule.
Three pathways that require this molecule are: fatty acid oxidation and reduction, pyruvate oxidation, the citric acid cycle (CAC), (also amino acid anabolism and catabolism, ketone body metabolism).
Acetyl‑CoA is an important molecule, because it is used in many reactions and links many different metabolic pathways. The function of this molecule is to move the C atoms in the acetyl group to the CAC and then transport electrons for ATP production.
What type of bond is the high energy bond in acetyl‑CoA?
The high energy bond in acetyl‑CoA is a thioester bond. Hydrolysis of this bond is highly exergonic (−31.5 kJ).
List three functions of cholesterol in the body.
- cell membrane structure,
- precursor of steroid hormones,
- precursor of vitamin D (also bile acid precursor).
What is the name of the pathway involved in the production of cholesterol?
Why is this pathway regulated?
How do levels of AMP affect the regulation of this pathway?
the isoprenoid pathway
Heavy energy requirement, so not good unless abundance of energy.
Inhibited by AMP presence as shows energy is low
The pathway involved in cholesterol synthesis is the isoprenoid pathway
Because it requires a large energy input, this pathway is regulated so that it will not run unless it is needed.
When concentrations of AMP are high, the cell doesn’t have a lot of energy to produce cholesterol. An AMP‑activated protein kinase inhibits HMG‑CoA reductase by phosphorylating it, which inhibits HMG‑CoA reductase and halts cholesterol production.
Why do you think HMG‑CoA reductase is an ideal target for cholesterol‑reducing medications?
A key enzyme in cholesterol production.
Statins used to competitively inhibit
Why are bile acids important in metabolism? What molecule is converted to bile acids?
Insoluble products such as dietary fibre, and waste products such as heme degradation products, must be efficiently eliminated by combination with a detergent.
A detergent molecule is one that combines with a non‑soluble molecule, giving a complex which can be suspended in solution rather than clumping with like insoluble molecules. The bile salts, cholic acid and deoxycholic acid, are the major biological detergents.
Cholesterol is the precursor of both cholic acid and deoxycholic acid.
Why do those on a strict vegetarian diet rarely suffer from diet–induced hypercholesterolemia?
Cholesterol is not found in plants; therefore, strict vegetarians rarely suffer from diet‑induced hypercholesterolemia.
Name the ketone bodies.
What is the role of these molecules in metabolism?
When are ketone bodies a source of energy?
acetoacetate, acetone, and D‑β‑hydroxybutyrate
The role of these molecules is to provide energy when glucose levels are low. They can be converted to acetyl‑CoA for entry into the citric acid cycle (CAC) and then ATP synthesis through the electron transport chain. Acetoacetate and β‑hydroxybutyrate can be converted to acetyl‑CoA. They can both cross the blood‑brain barrier and provide energy for the brain when glucose is limiting.
What is the connection between the citric acid cycle and oxaloacetate production and ketone body formation?
acetyl‑CoA from fatty acid breakdown enters the CAC, but oxaloacetate must be present to combine with acetyl‑CoA to form citrate
Oxaloacetate is usually regenerated each turn of the CAC, but in some cases it is used for other metabolism (drawn off) and is not present. If there is insufficient oxaloacetate, the acetyl‑CoA is converted to acetoacetate or β‑hydroxybutyrate. These ketone bodies can cross into the brain to provide energy and can be converted back into acetyl‑CoA as well.
How much energy can you obtain from the oxidation of palmitate, CH3 (CH2)14COOH, in the liver under conditions of ketosis?
How does this compare to the amount you can obtain when on a balanced diet providing glucogenic fuel molecules?
Estimates of energy release are most easily made by comparing the number of high‑energy electron carriers (NADH and FADH2) produced
Palmitate releases eight acetyl‑CoA fragments by seven rounds of β‑oxidation. Each round of β‑oxidation also yields one NADH and one FADH2 (a total of 14 high‑energy electron pairs).
This number is the same for normal and ketogenic conditions. Under normal conditions, each acetyl‑CoA, via the citric acid cycle, will reduce one FAD and 3NAD+ (a total of 32 high‑energy electron pairs, since there are eight acetyl‑CoA units).
This latter process is not possible under ketogenic conditions. Therefore ketogenic conditions provide ~30% of the energy that is available under normal conditions. Of course, the acetyl‑CoA units produced under ketogenic conditions are still available should conditions improve.
Excess acetyl‑CoA, produced by the citric acid cycle or by fatty acid breakdown, is channelled into ketone bodies. Would it be more sensible to provide a feedback mechanism to slow down the production of acetyl‑CoA itself?
Such a feedback mechanism would and would not be more sensible. Ketone bodies are produced under normal conditions and are the preferred fuel of, for example, heart tissue. The problem occurs when citric acid intermediates are in short supply and therefore the ketone bodies accumulate. There is some regulation of acetyl‑CoA production, but this molecule is at the heart of metabolism. Without it, you would die, so its synthesis is never shut down completely.
It was stated that one oxaloacetate molecule must be regenerated approximately every seven turns of the citric acid cycle. Since glycerol (from triacylglycerols) can produce oxaloacetate, and there are only seven to eight acetyl‑CoAs produced per fatty acid, why are ketone bodies produced at all?
A triacylglycerol produces one glycerol and three fatty acids. That is, one oxaloacetate for 21–24 acetyl‑CoA units.
How are ketone bodies funnelled back into central metabolism if citric acid cycle intermediates are synthesized?
Acetoacetate and β‑hydroxybutyrate are reconverted to acetyl‑CoA.
What biological advantage does storing major fuel reserves as fat rather than glycogen confer on nonplant species?
Non-poplar don’t attract water weight and bulk, which would hinder movement in a mobile creature.
Fats are insoluble, and so are not hydrated. Adipose cells—fat storage depots—contain droplets of triacylglycerol, much like drops of fat floating on the surface of water. Glycogen is a well‑hydrated molecule. To maintain the equivalent amount of energy reserves, a glycogen storer would be considerably heavier than a fat storer. This situation is not a good one if you are mobile and trying to escape predators.
Why are fat stores in mammalian adipose tissue sources of intracellular water?
Hydrolysis of the fat provides some water to the animal during dry desert work.
The complete oxidation of lipids yields carbon dioxide and water: roughly 1 mL water per gram of fat.
This relationship is a great advantage to camels, whose humps are fat depots.
What are the benefits of using β‑oxidation to metabolize lipids?
Makes insoluble fats soluble
reduces high energy particles
creates molecules (acetyl-CoA) for more energy production in the CAC
Conversion of a non‑reactive, insoluble hydrocarbon chain to a useful energy intermediate presents an immediate problem of solubility. The steps of β‑oxidation provide soluble fragments, as well as a high‑energy bond on each fragment, and an intermediate that can channel into an existing metabolic pathway (the citric acid cycle).
Marathon runners are said to “hit the wall” at about 20 miles, approximately the time the runner converts from carbohydrate to fat stores for energy. Why is this process so difficult that it is called a “wall”?
Fats, which are less soluble than carbohydrates, cannot be marshalled for use as quickly as can carbohydrates. The lipases in adipose tissue are soluble enzymes which must nibble at the edges of the fat droplets. As the fatty acids enter metabolism, their energy content, which is greater than that of carbohydrates, partially compensates for the slow start. This fact means that you can “get over the wall.”
A victim of starvation has to be fed small amounts of food and has to be very careful about introducing fat into the diet. Why?
A victim of starvation must be careful because the digestive and biosynthetic enzymes are produced on demand: no food = no enzymes. It normally takes three or more days for the enzymes to be synthesized (assuming amino acids are available to do so). The fatty acid degradative and biosynthetic enzymes are more slowly synthesized.
You add radiolabelled malonyl‑CoA to a cell extract which is actively synthesizing palmitate. (Each carbon of the malonyl unit is labelled by the isotope 14C.) You stop the reaction one minute later by altering the pH. Then you analyze the palmitate for radioactivity. Which of the carbons will be labelled in palmitate?
14C is carbon‑1; that is, carbon‑1 is radiolabelled, because a malonyl unit is added to the growing chain by insertion at the front.
