***TASK***
the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature
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Output:

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Input: Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.
Output:  When species evolve, their genes duplicate and diverge to allow for adaptation of their functional repertoires to the changing environment. In this scenario, unrelated genes can convergently evolve to produce proteins with the same molecular function, termed “functionally analogous.” A quantitative determination of the reaction similarities among functionally analogous enzymes could provide insight about the different structural solutions nature has used to evolve similar catalysts. Bond changes between substrates and products, and between successive reaction intermediates, were used to compare the reactions catalyzed and the mechanisms of catalysis for 95 pairs of functionally analogous enzymes. Less than half of the reactions catalyzed by unrelated enzymes, but defined as similar by the Enzyme Commission (EC) classification, are similar in terms of bond changes, suggesting that this classification often fails to capture quantitative differences between many enzyme reactions. Furthermore, we addressed for the first time whether the chemical mechanisms by which similar overall reactions are achieved in functional analogs are also similar. We conclude that convergence of reaction is often accompanied by convergence of chemical mechanism. These results will be useful for classifying enzymes, guiding functional annotation of newly determined enzyme sequences and structures and for informing the engineering of enzymes with new functions.

Input:  Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM).
Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies–Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10–14, 15–26, 23–31, and 33–39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15–26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42–0.96; P = 0.042) and 33% (0.67; 95% CI 0.45–0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10–14 and DGLA at GWs 10–14 and 15–26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15–26 was associated with a 45% (0.55; 95% CI 0.37–0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (<median) n-6 PUFAs levels had a 64% (95% CI 0.14–0.95; P value = 0.039) lower risk of GDM versus women with low n-3 and high n-6 PUFAs. Limitations include the inability to distinguish between exogenous and endogenous influences on circulating PUFA levels and the lack of causality inherent in observational studies.
Our findings may suggest a potential role of primarily endogenously metabolized plasma phospholipid n-6 PUFAs including GLA, DGLA, and DTA in early to midpregnancy in the development of GDM. Null findings on primarily diet-derived n-3 EPA and DHA and n-6 LA do not provide strong evidence to suggest a beneficial role in prevention of GDM, although not excluding the potential benefit of EPA and DHA on glucose–insulin homeostasis given the inverse associations with insulin-resistance markers. Our findings highlight the importance of assessing individual circulating PUFAs to investigate their distinct pathophysiologic roles in glucose homeostasis in pregnancy.


Output:

Dietary guidelines promote intakes of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, whereas evidence on PUFAs for pregnant women is scarce.
Experimental and observational studies have linked both dietary and circulating fatty acids to the risk of developing type 2 diabetes, insulin resistance, and β-cell dysfunction, but only a few studies did for the risk of developing gestational diabetes mellitus (GDM).
In particular, evidence is missing for the associations of individual plasma phospholipid PUFAs, rather than total PUFAs conventionally via dietary assessment, with the risk of subsequent GDM.
In this longitudinal study of 107 women with GDM and 214 matched non-GDM women within the prospective National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies–Singleton Cohort in the United States, we evaluated the associations of individual plasma phospholipid PUFAs in early to midpregnancy with a panel of glucose metabolism and cardiometabolic markers and subsequent risk of GDM.
Total and individual plasma phospholipid n-3 PUFAs—specifically, diet-derived eicosapentaenoic acid and docosahexaenoic acid—were inversely correlated with insulin-resistance markers but not associated with the risk of GDM.
Associations of individual plasma phospholipid n-6 PUFAs with GDM risk were differential, with no associations for the major diet-derived n-6 PUFAs (linolenic acid and arachidonic acid) comprising over 80% of total n-6 PUFAs and with null, positive, or negative associations for minor n-6 PUFAs recognized to be primarily produced from endogenous metabolism of linolenic acid.
No significant associations of major diet-derived n-6 PUFAs and significant findings for the other minor n-6 PUFAs known to reflect endogenous metabolism suggest a potential role of circulating levels of plasma phospholipid n-6 PUFAs in pathophysiology of GDM.
Furthermore, our findings do not provide strong evidence to suggest beneficial roles of primarily diet-derived n-3 PUFAs in prevention of GDM, although also not excluding the possibility of benefit on glucose–insulin homeostasis given their inverse correlations with insulin-resistance markers. Similarly, our findings suggest neither a harmful nor a beneficial role of diet-derived n-6 PUFA linolenic acid in GDM pathophysiology.
Our findings among pregnant women highlight the need to recognize the heterogeneous associations of individual circulating PUFAs with subsequent GDM risk and to investigate the underlying metabolism.
