Question

(13 points) A. Below is data collected for the reaction when metabolite Y is synthesized from metabolite X under two different conditions Plot the data na single graph and label all axes. (pts) Condition 1 reaction progress (beginning to end) free energy Condition 2 reaction progress (beginning to end) free energy 1 3 8.25 8.5 .75 4 8 6 8.25 9 3 10 4 10.5 5 6 8.25 7 4 8 1.5 91 10 1 8 1.5 91 10 11 B. Fully label all parts relevant parts of this graph that is required for correct interpretation. (6 points) C. For the reaction X Y , what does condition 1 and condition 2 represent? (1 pts) Y ? Does it change between Condition 1 and 2? Why or why D. Calculate the AG for the reaction of X not? (3 pts) 8. Opoints) EXTRA CREDIT A. Jack has genetic variations that increase the Knof ADH and decrease the K. of ALDH. He watches some basketball with his buddies and they cach have 8 beers during the course of the game. Explain the role of K. on enzyme activity and how these variants would most likely affects Jack in comparison to his friends during the game and the next morning. (It is given that all parties above are of drinking age and each has a designated driver. And for the record, that is way too much beer. If they keep drinking that way they may get fatty liver and a beer gut.) B. Decades ago, it was observed that the cells from liver cancer had an increased rate of glycolysis than normal cells. It was hypothesized that the intermediate metabolites in glycolysis were being used to produc the nucleic acids, fatty acids, and proteins to synthesize new cells. This inefficent use of glucose is coupled with pyruvate being converted to lactate rather than used for aerobic cellular respiration. These cells also had an increased expression of glucose transporters and hexokinase, along with other significant changes. support of this hypothesis, 1) why would these cells have an increase in glucose transporters and hexokinas and 2) hypothesize how hexokinase, PFK, and pyruvate kinase may regulated in some liver cancer cells. Support your answer. This answer is not meant to be researched or Googled, but answered based on what we learned in class about pathways and enzyme regulation. Google is not part of the scientific method.

Answer 1

8.A). A low Km value indicates a strong
affinity between enzyme and substrate, whereas
a high Km value reflects a weak affinity between
them..

Jack has high Km for ADH ie his alcohol metabolism will need high concentration of alcohol for 50% of his alcohol to be metabolised... This will cause prolonged effect of alcohol in his body......

He also has low Km for ALDH so small amount of acetaldehyde is converted fast into acetic acid leading to very minimal or no adverse effect of acetaldehyde in body...

Acetaldehyde interferes with DNA synthesis and repair, injures the cellular antioxidative defense system, especially through binding to glutathione, and results in cellular hyperregeneration of the mucosa of the upper alimentary tract and the colorectum.

Acetaldehyde also binds to DNA, generating stable adducts with mutagenic properties.

8.B. 1). Glucose uptake is the rate-limiting step in its use, underlining the importance of GLUT transporters in metabolism....

Liver cancercdisplay high rates of glucose uptake, exacerbated glucose consumption, including the increase of hexokinase expression , the decrease of glucose-6-phosphatase-mediated glucose dephosphorylation , and/or the overexpression of sugar transporters]. Agreed with this last explanation, GLUT1 overexpression has been observed in many human cancers. In addition, GLUT1 expression levels were inversely correlated with prognosis, as the deregulation of GLUT1 expression may reflect the presence of alterations in different signaling pathways.

HK2/hexokinase II, is one such attractive target in glucose metabolism, that catalyzes the irreversible rate-limiting step in the glycolytic pathway . Previous reports have revealed that HK2 is frequently upregulated in liver cancer tissues and is associated with poor patient outcomes .... normal differentiated hepatocytes, GCK is the major hexokinase (HK) isoform expressed; in HCC, GCK expression is repressed and expression of the fetal HK isoform, HK2, is induced7. Thus, in HCC cells, the predominantly expressed HK isoform is HK2; this distinguishes HCC cells from the normal surrounding adult hepatocytes. ...