Current Topics in Chemistry - Bruice

Dr. Glaser's "Chemistry is in the News"
To Accompany Bruice, Organic Chemistry, 3/e.
Chapter 19. Carbonyl Compounds III: Reactions at the Alpha-Carbon.

For each of the following questions, please refer to the following article:

A WORM AND A COMPUTER HELP ILLUMINATE DIABETES.
by Nicholas Wade (New York Times News Service, December 30, 1997)

Editorial Comments

Glucose metabolism is fundamental to mammals and its regulation is a complicated matter. Several hormones are involved in the regulation of the glucose level in the blood and diabetes results when this regulation becomes faulty. Diabetes affects about 5 percent of the population. Insulin is one hormone that is key to the regulation of the glucose metabolism and that has been known for some time. More recently, Donald L. Riddle, professor in the Division of Biological Sciences at the University of Missouri, has described a second pathway that is parallel to the insulin pathway for the control of the glucose metabolism genes. It appears that both pathways must be active for glucose metabolism to proceed.

The article describes how computational genetic data bank analysis and studies of worms are contributing to the understanding of both the regulation of the glucose metabolism and diabetes. The goal of the regulating pathways for the glucose metabolism is the determination as to whether gluconeogenesis or glycolysis should be active. The questions below will deal with a key step in the biosynthesis and the decomposition of glucose.

Incidently, I got a good laugh out of reading the sentence "a microscopic roundworm called Caenorhabditis elegans, a standard laboratory organism surprisingly similar to humans."

Pertinent Text References
Chapter 19. Carbonyl Compounds III. Reactions at the alpha-Carbon.
Section 19.21. Reactions at the alpha-Carbon in Biological Systems.
Chapter 20. Box on "Measuring the Blood Glucose Level of Diabetics".
Chapter 21. Amino Acids, Peptides, and Proteins.
Chapter 22.8. Catalysis in Biological Reactions.

Questions

Question 1: Explain the terms "gluconeogenesis" and "glycolysis" and provide the structures of D-glucose and of pyruvate.

Answer 1: Bruice 3/e, Chapter 19, page 863.

Question 2: A key step in the glucose metabolism is the aldol reaction of dihydroxyacetone phosphate and D-glyceraldehyde-3-phosphate. Propose a mechanism for this reaction using hydroxide ion as the catalyst.

Answer 2: Bruice 3/e, Chapter 19, page 863.

Question 3: In vivo the aldol reaction of dihydroxyacetone phosphate and D-glyceraldehyde-3-phosphate is catalyzed by the enzyme aldolase. The active site of aldolase contains (a) a lysine residue, (2) a histidine residue and (3) a cysteine residue. Explain how these residues participate in the aldol addition reaction.

Answer 3: Bruice 3/e, Chapter 22, page 985.

Question 4: Examine the X-ray structure of the enzyme aldolase. Can you find the active site? Can you see the lysine residue, the histidine residue and the cysteine residue?

Answer 4: Takes time!

Chemistry & Society.
The current topic provides an interesting case study of the synergism between science and research and the funding policies. Tak a look at the Recommendations of the Congressionally Directed Diabetes Research Working Group. The scientific recommendations in the DRWG Strategic Plan are divided into three main categories and the first of these is "Extraordinary Opportunities". Among the "Extraordinary Opportunities", research on "Genetics of Diabetes and its Complications" is listed as the first one.