A Molecular Caliper Mechanism for Determining

The article is about the discovery of a molecular “caliper” that can be used to measure the length of very long-chain fatty acids (VLCFA). It was written by Vladimir Denic and Dr. Jonathan Weissman. Here, I will analyze the important elements in this scientific paper by answering the key questions below.

1. What important previously observed facts stimulated the new work? (Background)

It has been observed that very long-chain fatty acids (VLCFAs) are responsible for the cellular growth and alterations in the length of these fatty acids will result to abnormalities. In humans, Very Long Chain Acyl-CoA Dehydrogenase Deficiency (LCAD) and adrenoleukodystrophy (ALD) are two of the metabolic diseases that can be fatal to the individual (“Very Long Chain Acyl-CoA Dehydrogenase”; Kemp and Watkins “Very Long Chain Fatty Acids and Adrenoleukodystrophy”).

One possible way to solve this problem is by determining the lengths of VLCFAs. It is also important to note that VLCFAs are results of catalytic processes. Thus, the different components of VLCFAs as well as the proteins responsible for this must be determined.

In the article, previous studies conducted on the process of converting short fatty acids were included. The four steps in the metabolic process were listed (Denic and Weissman 663). After it, the researchers investigated on the missing links of the process: the novel dehydratase and the elongase protein (Elop) which acts as “scissors” in the elongation cycle. Using complicated steps derived from previous experiments, they were able to identify the Elop known as Phs1p.

Unknown to the researchers are the Elop responsible for determining the length of the resultant VLCFAs by stopping Phs1p from elongating the fatty acid. Another unknown is the method which the researchers can determine the length of the VLCFA.

2. What is the hypothesis of the new work?

The hypothesis of this work can be found in the abstract but it is a shorter version and probably needs elaboration. By analyzing the existing data on VLCFA, the researchers have come up with the hypothesis that FAs are elongated to VLCFAs by three membrane components (Denic and Weissman 663). Also, they were able to hypothesize that the length of the VLCFA can be measured by determining the distance from the lysine residue and the Elop active sites (Denic and Weissman 663).

3. What are the major findings reported in the manuscript? (New data)

The major findings in the article include the discovery of the missing component—novel dehydratase–Phs1p. This is the component responsible for the elongation of the FAs (Denic and Weissman 664). Now, the researchers still looked for the Elop responsible for the length determination of the VLCFAs and found two examples of this component, namely Fen1p and Sur4p (Denic and Weissman 674). By undergoing in vivo tests, they were able to isolate the Elops and found out that Fen1p and Sur4p is responsible for the elongation of C18 fatty acids into C22 and C26 respectively (Denic and Weissman 674).

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