Substituting dietary linoleic acid with α-linolenic acid improves insulin sensitivity in sucrose fed rats

This study describes the effect of substituting dietary linoleic acid (18:2 n-6) with α-linolenic acid (18:3 n-3) on sucrose-induced insulin resistance (IR). Wistar NIN male weanling rats were fed casein based diet containing 22 energy percent (en%) fat with ～6, 9 and 7 en% saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) respectively for 3 months. IR was induced by replacing starch (ST) with sucrose (SU). Blends of groundnut, palmolein, and linseed oil in different proportions furnished the following levels of 18:3 n-3 (g/100 g diet) and 18:2 n-6/18:3 n-3 ratios respectively: ST-220 (0.014, 220), SU-220 (0.014, 220), SU-50 (0.06, 50), SU-10 (0.27, 10) and SU-2 (1.1, 2). The results showed IR in the sucrose fed group (SU-220) as evidenced by increase in fasting plasma insulin and area under the curve (AUC) of insulin in response to oral glucose load. In SU-220, the increase in adipocyte plasma membrane cholesterol/phospholipid ratio was associated with a decrease in fluidity, insulin stimulated glucose transport, antilipolytic effect of insulin and increase in basal and norepinephrine stimulated lipolysis in adipocytes. In SU-50, sucrose induced alterations in adipocyte lipolysis and antilipolysis were normalized. However, in SU-2, partial corrections in plasma insulin, AUC of insulin and adipocyte insulin stimulated glucose transport were observed. Further, plasma triglycerides and cholesterol decreased in SU-2. In diaphragm phospholipids, the observed dose dependent increase in long chain (LC) n-3 PUFA was associated with a decrease in LC-n-6 PUFA but insulin stimulated glucose transport increased only in SU-2. Thus, this study shows that the substitution of one-third of dietary 18:2 n-6 with 18:3 n-3 (SU-2) results in lowered blood lipid levels and increases peripheral insulin sensitivity, possibly due to the resulting high LCn-3 PUFA levels in target tissues of insulin action. These findings suggest a role for 18:3 n-3 in the prevention of insulin resistant states. The current recommendation to increase 18:3 n-3 intake for reducing cardiovascular risk may also be beneficial for preventing IR in humans.     

The role of autophagy in neonatal tissues: just a response to amino acid starvation?

Autophagy is activated soon after birth in neonatal tissues and is essential for survival because mice deficient in Atg5 or Atg7 autophagy genes die within 1 day after birth. Amino acid starvation has been considered as a major deleterious effect of autophagy deficiency, since the concentration of amino acids in plasma was decreased by 20% in the two knockout models, whereas blood glucose and fatty acid levels were apparently not affected. However, autophagy may have other important functions in neonatal physiology, including glycogen degradation, programmed cell remodeling and response to oxidative stress.     

Maternal modulation of natal dispersal in a passerine bird: an adaptive strategy to cope with parasitism?

The decision of how far to disperse from the natal territory has profound and long-lasting consequences for young animals, yet the optimal dispersal behavior often depends on environmental factors that are difficult or impossible to assess by inexperienced juveniles. Natural selection thus favors mechanisms that allow the adaptive and flexible adjustment of the offspring's dispersal behavior by their parents via either paternal or maternal effects. Here we show that different dispersal strategies maximize the reproductive success of young great tits (Parus major) originating from a parasite-infested or a parasite-free nest and demonstrate that differential transfer of maternal yolk androgens in response to parasitism can result in a modification of the offspring's dispersal behavior that appears adaptive. It demonstrates that prenatal maternal effects are an important yet so far neglected determinant of natal dispersal and highlights the potential importance of maternal effects in mediating coevolutionary processes in host-parasite systems.     

Is there evidence for a common amino acid sequence in proteins with membrane attaching ability?

A comparison between the primary sequence of staphylococcal protein A (SpA) and a wide range of published protein sequences revealed a limited, but striking homology in approximately two-thirds of them. The region in the SpA sequence with the common homology was identified as the octapeptide repeats comprising the cell wall peptidoglycan-binding domain. Available structural information and the known location of the proteins within their host cells suggests that this common octapeptide may be important in interaction of the protein with the cell surface (either membrane or wall).     

How to cope with insect resistance to Bt toxins?

Transgenic Bt crops producing insecticidal crystalline proteins from Bacillus thuringiensis, so-called Cry toxins, have proved useful in controlling insect pests. However, the future of Bt crops is threatened by the evolution of insect resistance. Understanding how Bt toxins work and how insects become resistant will provide the basis for taking measures to counter resistance. Here we review possible mechanisms of resistance and different strategies to cope with resistance, such as expression of several toxins with different modes of action in the same plant, modified Cry toxins active against resistant insects, and the potential use of Cyt toxins or a fragment of cadherin receptor. These approaches should provide the means to assure the successful use of Bt crops for an extended period of time.     

Is there a twenty third amino acid in the genetic code?

The universal genetic code includes 20 common amino acids. In addition, selenocysteine (Sec) and pyrrolysine (Pyl), known as the twenty first and twenty second amino acids, are encoded by UGA and UAG, respectively, which are the codons that usually function as stop signals. The discovery of Sec and Pyl suggested that the genetic code could be further expanded by reprogramming stop codons. To search for the putative twenty third amino acid, we employed various tRNA identification programs that scanned 16 archaeal and 130 bacterial genomes for tRNAs with anticodons corresponding to the three stop signals. Our data suggest that the occurrence of additional amino acids that are widely distributed and genetically encoded is unlikely.     

Occurrence of trans fatty acids in rats fed a trans-free diet: A free radical-mediated formation?

Trans isomers of unsaturated fatty acids are absorbed from the diet, due to their presence in diary fat and hydrogenated vegetable oils, and health concern has risen due to their effects on lipid risk factors in cardiovascular diseases. On the basis of the efficiency of the thiyl-radical-catalyzed cis/trans isomerization in vitro and the presence of many sulfur-containing compounds in the cell, the aim of this study was to demonstrate that trans geometry of lipid double bonds can be endogenously generated within membrane phospholipids. The study reports trans fatty acids occurrence in tissue and erythrocyte phospholipids of young adult rats fed a diet completely free of trans isomers. Results show that tissues are differently prone to the endogenous isomerization and that, following a free radical attack, trans fatty acids can reach very high amounts. The effectiveness of this process is considerably inhibited in the presence of all-trans retinol, confirming previous data in model membranes. Our results suggest that geometrical isomerization of unsaturated fatty acids, which causes a structural modification of membrane lipids and may influence basic membrane properties and vital biochemical functions, can occur under radical stress conditions and could be efficiently prevented by vitamin A.     

Differences in properties between aromatic amino acid: Aromatic keto acid aminotransferases and aromatic amino acid: α-ketoglutarate aminotransferases

Homogenates of rat liver transaminate phenylpyruvate (PP), as well as α-ketoglutarate (α-KG), in the presence of L-tyrosine, 3,4-dihydroxyphenylalanine (L-DOPA) or L-tryptophan. Aminotransferase activity with phenylpyruvate and DOPA, but not with tyrosine, was inhibited by excess phenylpyruvate. Tyrosine and DOPA aminotransferase activities with phenylpyruvate were more heat stable than the corresponding activities with α-ketoglutarate. Aminotransferase activities with phenylpyruvate were not significantly induced following intraperitoneal injections of cortisol, glucagon or serotonin, compared with a 3 to 7-fold increase in the aminotransferase activities with α-ketoglutarate. Tyrosine:phenylpyruvate aminotransferase activity rose 40% at night, compared with a 300% increase in tyrosine:α-ketoglutarate aminotransferase activity. The results suggest that aminotransferases catalysing transfers between aromatic keto acids and aromatic amino acids are separate enzymes from those utilizing α-ketoglutarate as the acceptor keto acid.     

Does phosphoenolpyruvate carboxykinase have a role in both amino acid and carbohydrate metabolism?

Summary. Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the reversible decarboxylation of oxaloacetate to yield phosphoenolpyruvate and CO₂. The role of the enzyme in gluconeogenesis and anaplerotic reactions in a range of organisms is discussed, along with the important function in C₄ and CAM photosynthesis in higher plants. In addition, new data are presented indicating that PEPCK may play a key role in amino acid metabolism. It is proposed that PEPCK is involved in the conversion of the carbon skeleton of asparagine/aspartate (oxaloacetate) to that of glutamate/glutamine (2-oxoglutarate). This metabolism is particularly important in the transport system, seeds and fruits of higher plants. Received January 27, 2000 Accepted March 7, 2000     

Adrenic acid Δ4 desaturation and fatty acid composition in the liver of marine-oil fed streptozotocin diabetic rats

The aim of the present study was to assess the effect of streptozotocin diabetes and insulin treatment on adrenic acid Δ4 desaturation and fatty acid composition of liver microsomes in Wistar rats fed a fat free semi-synthetic basal diet supplemented with 10% EPA-rich marine oil. Results showed that, in liver microsomes of hyperglycemic rats, the ratio in total lipids was elevated and desaturation of adrenic acid to n-6 docosapentaenoic acid was enhanced. Insulin treatment with 2.0 I.U./100 g body weight⁻¹ twice a day for 3 days resulted in hypoglycemia and suppressed both the increased Δ4 n-6 desaturation and ratio. It is concluded that the Δ4 desaturation enzyme system, which is activated by experimental diabetes, is regulated by mechanisms different from those regulating Δ6 and Δ5 desaturations.     

Twelve positions in a β-lactamase that can expand its substrate spectrum with a single amino acid substitution

The continuous evolution of β-lactamases resulting in bacterial resistance to β-lactam antibiotics is a major concern in public health, and yet the underlying molecular basis or the pattern of such evolution is largely unknown. We investigated the mechanics of the substrate fspectrum expansion of the class A β-lactamase using PenA of Burkholderia thailandensis as a model. By analyzing 516 mutated enzymes that acquired the ceftazidime-hydrolyzing activity, we found twelve positions with single amino acid substitutions (altogether twenty-nine different substitutions), co-localized at the active-site pocket area. The ceftazidime MIC (minimum inhibitory concentration) levels and the relative frequency in the occurrence of substitutions did not correlate well with each other, and the latter appeared be largely influenced by the intrinsic mutational biases present in bacteria. Simulation studies suggested that all substitutions caused a congruent effect, expanding the space in a conserved structure called the omega loop, which in turn increased flexibility at the active site. A second phase of selection, in which the mutants were placed under increased antibiotic pressure, did not result in a second mutation in the coding region, but a mutation that increased gene expression arose in the promoter. This result suggests that the twelve amino acid positions and their specific substitutions in PenA may represent a comprehensive repertoire of the enzyme's adaptability to a new substrate. These mapped substitutions represent a comprehensive set of general mechanical paths to substrate spectrum expansion in class A β-lactamases that all share a functional evolutionary mechanism using common conserved residues.     

β-Keratins in crocodiles reveal amino acid homology with avian keratins

The DNA sequences encoding β-keratin have been obtained from Marsh Mugger (Crocodylus palustris) and Orinoco Crocodiles (Crocodylus intermedius). Through the deduced amino acid sequence, these proteins are rich in glycine, proline and serine. The central region of the proteins are composed of two beta-folded regions and show a high degree of identity with β-keratins of aves and squamates. This central part is thought to be the site of polymerization to build the framework of β-keratin filaments. It is believed that the β-keratins in reptiles and birds share a common ancestry. Near the C-terminal, these β-keratins contain a peptide rich in glycine-X and glycine-X-X, and the distinctive feature of the region is some 12-amino acid repeats, which are similar to the 13-amino acid repeats in chick scale keratin but absent from avian feather keratin. From our phylogenetic analysis, the β-keratins in crocodile have a closer relationship with avian keratins than the other keratins in reptiles.     

Serum amino acid profiles and dopamine in schizophrenic patients and healthy subjects: Window to the brain?

Summary Altered dopamine turnover has been postulated as underlying cause for schizophrenia. This is partially inferred from pharmacological studies and from changes in serum dopamine and dopamine metabolite levels. It is not clear whether the serum amino acid precursors' availability and neurotransmitter-mediated hormonal release could be indicative of the neurotransmitter turnover. We speculate in this context that the profile of serum amino acids and neurotransmitters reflects differences of neurotransmitter activity in the central nervous system and may be considered in a broad sense window to the brain.We analyzed basal serum amino acids (including monoamine precursors), and monoamines in schizophrenic patients after a drug holiday of 3 or more days, and in healthy subjects.Asparagine, phenylalanine, and cystine were higher and tyrosine, tryptophan, and the ratio of tryptophan to competing amino acids lower in schizophrenic patients than in healthy subjects (P < 0.05). Dopamine was increased in schizophrenic patients compared to healthy subjects.We speculate that these results sustain the notion for dopamine overactivity in schizophrenia, which might be caused by altered amino acid precursor availability.Presented at the 2nd International Congress on Amino Acids and Analogues, Vienna, Austria August 5–9, 1991     

Is glycine a surrogate for a d‐amino acid in the collagen triple helix?

Collagen is the most abundant protein in animals. Every third residue in a collagen strand is a glycine with phi, psi = -70 degrees, 175 degrees. A recent computational study suggested that replacing these glycine residues with D-alanine or D-serine would stabilize the collagen triple helix. This hypothesis is of substantial importance, as the glycine residues in collagen constitute nearly 10% of the amino acid residues in humans. To test this hypothesis, we synthesized a series of collagen mimic peptides that contain one or more D-alanine or D-serine residues replacing the canonical glycine residues. Circular dichroism spectroscopy and thermal denaturation experiments indicated clearly that the substitution of glycine with D-alanine or D-serine greatly disfavors the formation of a triple helix. Host-guest studies also revealed that replacing a single glycine residue with D-alanine is more destabilizing than is its replacement with L-alanine, a substitution that results from a common mutation in patients with collagen-related diseases. These data indicate that the glycine residues in collagen are not a surrogate for a D-amino acid and support the notion that the main-chain torsion angles of a glycine residue in the native structure (especially, phi > 0 degrees ) are critical determinants for its beneficial substitution with a D-amino acid in a protein.