Glycogen storage disease type 1a is a serious genetic disorder that can result from a defect in the gene encoding glucose-6-phosphatase. The enzyme catalyzes the production of glucose from glucose-6-phosphate, an intermediate in the breakdown of glycogen. Little is known concerning the mechanism by which the enzyme operates and still less about defects in the enzyme that lead to glycogen storage disease. One mutation in glucose-6-phosphatase that has been found to produce the disease is a change from glycine to arginine in a region of the protein thought to span membranes within the cell. The authors found that the mutation affects catalytic activity of the enzyme and sought to understand the basis of this effect.

Mutations were made in the gene encoding glucose-6-phosphatase at codon 222, which normally specifies glycine. The mutations changed the encoded amino acid from glycine to one of ten alternative amino acids. The mutant genes were introduced into cells and, after some time for the genes to express the enzyme, the cells were broken and glucose-6-phosphatase activity measured. As a control, enzyme activity was measured in cells that were given the wild-type gene or no gene at all.

Glucose-6-phosphatase containing arginine at position 222 (as is the case with some patients with glycogen storage disease) exhibited only 4% of the activity of the wild-type enzyme, little different from the activity obtained from cells with no introduced gene at all. Maybe the cells had a small amount of their own glucose-6-phosphatase. Mutant enzymes with different amino acids at position 222 had greater activity, high (>50% wild-type activity) with amino acids that are hydrophobic or small, uncharged hydrophilic) or low (20%-27% activity) with amino acids that are charged or large, uncharged hydrophilic). Evidently charged or bulky hydrophilic amino acids disrupt the membrane-spanning region of the enzyme sufficiently to prevent normal enzymatic activity. The largest charged amino acid, arginine, has so great an effect as to abolish activity altogether, leading to the disease phenotype.

Paragraph 1 (Introduction of problem):

• I started with the part of the article that was of greatest interest to me and possibly to the reader: the connection between a human disease state and its underlying cause.
• From there I went in small steps to the last sentence, which states the question that served as the focus for the remainder of the summary.
• Note that the question I chose is just one of several the authors addressed. I did not mention the others at all.
• I used no abbreviations, hoping to relieve the burden on the reader: no GSD, no G6P, no G222R.
• I introduced only what I thought was necessary to understand my review. For example, it is necessary to say that the enzyme spans a membrane, since the mutation I'm interested in lies within the membrane. I don't have to say how many membrane-spanning regions there are.

Paragraph 2 (Approach):

• Hardly anything remains from the Materials and Methods except for the main point of how the experiment was conducted.
• While virtually all detail is omitted, it is still possible to follow the experiment from the beginning to the end, thereby understanding how the results were obtained.
• There are a lot of judgment calls. I judged that it didn't matter how the genes got into the cells nor how the mutations were made.
• I don't know what COS cells are, and I did not pass my ignorance on to the reader. If I felt that my story required knowing what kind of cells were used, I would need to find out somehow, using resources besides the article itself.

Paragraph 3 (Results):

• I related specific results, with specific numbers.
• I tried to help the reader make sense out of those numbers.
• I didn't give all the results, just those that helped me tell my story.
• I didn't shrink from indicating the limits of my knowledge (i.e., why the negative control still had some apparent activity).
• I tried to relate the results to the larger issue with which I began my summary.
• I presented results of experiments in past tense, general conclusions in present tense.