Question

Problem 1. One of the consequences of ethanol addiction is fatty liver disease, an illness in which liver cells accumulate large amounts of triacylglycerols, the esters derived from glycerol and fatty acids. Ethanol is oxidized in the cytoplasm of liver cells by alcohol dehydrogenase and aldehyde dehydrogenase to yield acetate and 2 NADH. Acetate is then transported into the mitochondrion, where it is converted to acetyl-CoA and metabolized in the citric acid cycle.

1. Give a reason based on the products of ethanol metabolism and the electron transport chain for high energy charge in the cell
2. How would excess G6P concentration contribute to the reducing potential required for fatty acid synthesis?
3. How does acetate stimulate the rate of citrate formation based on enzyme kinetic?
4. How would the concentration of citrate in the mitochondria increase if the rate of isocitrate dehydrogenase rate were inhibited
5. What would inhibit the rate of isocitrate dehydrogenase if ethanol metabolism causes high-energy charge.

Answer 1

A. Alcohol is metabolized through different reactions -one of them is oxidation/reduction reactions.There are mainly two oxidation reactions. Convertion of alcohol to acetaldehyde by the enzyme alcohol dehydrogenase by removing two electrons and convertion of acetaldehyde into acetate by removing two additional electrons by enzyme aldehyde dehydrogenase. Then a hydroxyl ion from a water molecule is added. So, the electrons thus removed are transferred to a molecule, nicotinamide adenine dinucleotide (NAD), then converted to reduced NADH. These NADH can release the electrons into the mitochondrial electron transport system from where electrons are transferred to a series of molecules and made itself available for another electron acceptor. Then the electrons are used to generate water. Such electron transfer reactions release enough energy forming enough ATP molecules. Finally, ATP from two precursor molecules, adenosine diphosphate (ADP) and inorganic phosphate (Pi) are synthesized.

B. Glucose 6-phosphate(G6P) is produced from the phosphorylation of glucose on the sixth carbon. It can also be produced during glycogenolysis from glucose 1-phosphate. If the ratio of NADP+ to NADPH increases, more NADPH are produced by the body. These cellular NADPH can be used as a reducing agent for biosynthesis of fatty acid and cholesterol. Moreover G6PD in adipocytes play role in energy homeostasis, like lipid and glucose metabolism. Thus, it helps in dysregulation of lipid metabolism and insulin resistance in obesity. The excess levels of G6PD stimulated the expression of many adipocyte marker genes. Not only that it also increases the levels of cellular free fatty acids, triglyceride and FFA release.