Alternative Pathways - Biochemistry

Fats are broken down into acetyl-CoA to be used for energy. However, large quantities of alcohol will produce large quantities of acetyl-CoA when metabolized. Acetyl-CoA can be converted into fatty acids when it is in excess. Then fatty acids can assemble into triglycerides and be stored as fat.

In the absence of oxygen, oxidative phosphorylation cannot be used to produce ATP, so glycolysis becomes the primary source of ATP for the cell. The importance of lactic acid fermentation is that it replenishes cellular for the glyceraldehyde-3-phosphate dehydrogenase reaction, which precedes the ATP-producing steps. Without lactic acid fermentation, concentrations would become too low for the glyceraldehyde-3-phosphate dehydrogenase reaction to occur, and the ATP-producing steps would not continue to be reached.

When glucose is fermented, it forms the product lactate. Lactate can then continue on to be fermented to acetate. However, the other answer choices do not represent the correct direction from reactant to product in fermentation. In some organisms, ethanol and carbon dioxide may be produced via fermentation, but carbon dioxide is a byproduct, not a major product in these organisms.

NADH is, under aerobic conditions, returned to when it has its electrons taken in the electron transport chain. However, anaerobic conditions disallow this from occurring, and so NADH will build up in the cell. Fermentation is a pathway that allows pyruvate to be converted to either ethanol or lactic acid (depending on the organism) in order to regenerate the supply of .

Fermentation take place when there is a lack of oxygen in a cell. Without oxygen, the only process that can create ATP from glucose is glycolysis. However, NADH is created during glycolysis, and must be turned back to in order to continue metabolizing glucose with glycolysis. Fermentation, therefore, has the main responsibility of regenerating .

As alluded to in the question stem, an abundance of oxygen allows aerobic respiration to proceed. This allows glucose to be oxidized completely to yield a high amount of energy. In contrast, when oxygen is scarce, cells revert to an alternative method of producing energy, but one that is far less efficient. This is known as anaerobic respiration.

Though there are different types of anaerobic respiration, the one relevant to this question is lactic acid fermentation. In this process, the pyruvate coming from glycolysis is converted into lactic acid. When this happens, NADH is also oxidized back into its non-reduced form. This is the reason why fermentation occurs. If all of the cell's NAD were to be in its reduced form, then there's no way that glycolysis could proceed. Since glycolysis doesn't rely on oxygen, this is the only pathway to provide a stable energy source during oxygen deprivation. So in order to regenerate the needed for glycolysis to continue, it needs to donate its electrons onto pyruvate, which produces lactic acid.

Because the sprinter is exercising at a high intensity, his body is metabolizing its fuel under anaerobic conditions. Lactic acid fermentation is the conversion of pyruvate to lactate, and occurs only under anaerobic conditions. Glycolysis always occurs under anaerobic conditions, and glucose needs to be broken down to fuel the sprinter. The Cori cycle is the process that describes anaerobic metabolism on a larger scale (the conversion of glucose to pyruvate, to lactate, and back to glucose). Finally, because the athlete is using up his glucose, glycogenolysis will occur in order to convert some of his stored glucose (glycogen) to blood glucose.

The only answer choice remaining is gluconeogenesis. Gluconeogenesis and glycolysis occurring at the same time would be called a "futile cycle". They are opposing pathways, and if one is occurring, there is no need for the other to occur, that would be wasteful. We already established that glycolysis was occurring, so it is unlikely that gluconeogenesis would also occur.

Under normal aerobic conditions, the final electron acceptor at the end of the electron transport chain is oxygen. However, fermentation occurs when there is no oxygen available. Therefore, something else must act as the final electron acceptor. In lactic acid fermentation, NADH is the electron carrier that ultimately carries them to pyruvate. Pyruvate is reduced to lactic acid, and thus, acted as the final electron acceptor.

Answering this question requires knowledge of the pathway of gluconeogenesis. In this pathway, non-carbohydrate carbon substrates such as lactate, pyruvate, and certain amino acids are used to generate glucose as the final product. Much of this pathway utilizes the same enzymes used in glycolysis, which is essentially the reverse of gluconeogenesis. However, it is critical to note that there are 3 reactions in glycolysis that are irreversible. Therefore, gluconeogenesis is not an exact reverse of glycolysis, and instead there are a few different enzymes in gluconeogenesis that bypass these irreversible reactions. One of the irreversible steps in glycolysis is the formation of pyruvate from phosphoenolpyruvate (PEP), catalyzed by the glycolytic enzyme pyruvate kinase. To bypass this irreversible reaction, gluconeogenesis makes use of two enzymes. First, the enzyme pyruvate carboxylase converts pyruvate into oxaloacetate, which requires the input of one molecule of ATP per molecule of pyruvate used. Next, the gluconeogenic enzyme PEP carboxykinase converts oxaloacetate into PEP, using one molecule of GTP per molecule of oxaloacetate used. The other step that requires an investment of energy is by a reaction that is reversible. The conversion of 3-phosphoglycerate into 1,3-bisphosphoglycerate (1,3-BPG) by the enzyme phosphoglycerate kinase utilizes one molecule of ATP per molecule of 1,3-BPG generated. This is a reversible reaction. Now, we can add up the energy requirements. Since each of these reactions need to occur twice in order to generate a single molecule of glucose, we'll need to multiply the energy investment by two in each step. Thus, we have two molecules of ATP from the reaction catalyzed by pyruvate carboxylase. We also have two molecules of GTP from the reaction catalyzed by PEP carboxykinase. And lastly, we have two molecules of ATP used from the reaction catalyzed by phosphoglycerate kinase. Adding all of these up, we have a total of four molecules of ATP and two molecules of GTP.

In the first step of gluconeogenesis, pyruvate carboxylase (with ATP and bicarbonate) converts pyruvate to oxaloacetate. Then phosphoenolpyruvate carboxykinase (PEPCK) (with GTP) releases carbon dioxide to give phosphoenolpyruvate.

GTP and ATP are used to drive the reactions that make pyruvate into PEP. Specifically, ATP catalyzes PEP carboxylase and GTP catalyzes PEP carboxykinase. A mutase moves phosphate groups already on a molecule, so it cannot be used to introduce one. The citric acid cycle can make pyruvate into any of the citric acid intermediates, but PEP isn't one of them. Pyruvate kinase is the enzyme that makes pyruvate into PEP, which is only favorable in the forward direction.

Futile cycling occurs when two metabolic processes occur in opposite directions, and thus result in no net change. This is very wasteful, and not ideal. The only example of the answer choices of metabolic processes occurring in opposite directions is glycolysis and gluconeogenesis occurring simultaneously. Other possible examples could include: glycogenesis and glycogenolysis, beta-oxidation and fatty acid synthesis, etc.

Gluconeogenesis occurs in times of starvation, fasting, and low access to sources of glucose. This is the cells way of creating its own precursor when none is available, albeit at a high energetic cost (one cycle of gluconeogenesis can cost 6 ATP). Thus, it is untrue that gluconeogenesis occurs during high consumption of carbohydrates and fatty acids. Each other selection is true regarding gluconeogenesis.

The Cori cycle comes into play during anaerobic conditions; where lactate from glycolysis travels from the muscle to the liver to be converted into glucose via gluconeogenesis. The glucose is then sent back to the muscle to be used for energy. Note that some of the lactate that is converted into glucose can be stored as glycogen in the liver, but glycogen is not transported from the liver to the skeletal muscle.

Oxaloacetate contributes to fatty acid synthesis, but it’s not a lipid, because, among other reasons, it’s not hydrophobic. This is also why it cannot cross mitochondrial membranes. Glucose can be synthesized from glycerol, but this process occurs via dihydroxyacetone phosphate, and doesn’t involve oxaloacetate. Oxaloacetate is synthesized from pyruvate, which is the end product of glycolysis, so oxaloacetate cannot be an intermediary in glycolysis. However, lactate can be converted to pyruvate, which is the principle substrate for gluconeogenesis (sometimes called “reverse glycolysis”). In gluconeogenesis, oxaloacetate is an intermediary in the conversion of pyruvate to phosphoenolpyruvate, and so that makes it an intermediary, too, in the synthesis of glucose from lactate.

Oxaloacetate is the four-carbon molecule that is regenerated by the enzyme malate dehydrogenase in order to continue the cycle to form citrate with acetyl-CoA in the first step of the Krebs cycle. The other answer choices are intermediates of the citric acid cycle, but only oxaloacetate is regenerated, making it a true cycle.

When glycogen phosphorylase reaches a branching point in glycogen, the bonds switch from being alpha-1,4-glycosidic bonds to alpha-1,6-glycosidic bonds. It is unable to cleave these bonds, and so other enzymes (a transferase and a glucosidase) must come into play.

Glycogen is first debranched and broken down from its non-reducing end by glycogen phosphorylase to give the product G1P, which is then converted into G6P by phosphoglutomutase. Glycogen synthase, glycogen branching enzyme, and UDP-glucose pyrophosphorylase are required for glycogen synthesis.

In order to break down glycogen into individual glucose-6-phosphate units, all of the above enzymes are required. Each plays a specific role in one of the following activities: degradation of glycogen initially, remodeling of the glycogen so that it can be acted upon by the enzymes, and conversion of glucose-1-phosphate to glucose 6-phosphate.

Glycogen phosphorylase, the rate-limiting enzyme of glycogenolysis does not breaks alpha 1,6 glycosidic bonds. It releases glucose from glycogen by hydrolyzing alpha 1,4 glycosidic bonds until it reaches a branch point in the glycogen molecule. At this time, another enzyme, a debranching alpha 1,6 glycosidase hydrolyzes the alpha 1,6 glycosidic bonds. Glycogen phosphorylase is under regulation by many hormones, including insulin and glucagon, as well as epinephrine.