1.Loss of Mitochondrial Pyruvate Carrier 2 in the Liver Leads to Defects in Gluconeogenesis and Compensation via Pyruvate-Alanine Cycling.
McCommis KS;Chen Z;Fu X;McDonald WG;Colca JR;Kletzien RF;Burgess SC;Finck BN Cell Metab. 2015 Oct 6;22(4):682-94. doi: 10.1016/j.cmet.2015.07.028. Epub 2015 Sep 3.
Pyruvate transport across the inner mitochondrial membrane is believed to be a prerequisite for gluconeogenesis in hepatocytes, which is important for the maintenance of normoglycemia during prolonged food deprivation but also contributes to hyperglycemia in diabetes. To determine the requirement for mitochondrial pyruvate import in gluconeogenesis, mice with liver-specific deletion of mitochondrial pyruvate carrier 2 (LS-Mpc2(-/-)) were generated. Loss of MPC2 impaired, but did not completely abolish, hepatocyte conversion of labeled pyruvate to TCA cycle intermediates and glucose. Unbiased metabolomic analyses of livers from fasted LS-Mpc2(-/-) mice suggested that alterations in amino acid metabolism, including pyruvate-alanine cycling, might compensate for the loss of MPC2. Indeed, inhibition of pyruvate-alanine transamination further reduced mitochondrial pyruvate metabolism and glucose production by LS-Mpc2(-/-) hepatocytes. These data demonstrate an important role for MPC2 in controlling hepatic gluconeogenesis and illuminate a compensatory mechanism for circumventing a block in mitochondrial pyruvate import.
2.C-C chemokine receptor 3 antagonism by the beta-chemokine macrophage inflammatory protein 4, a property strongly enhanced by an amino-terminal alanine-methionine swap.
Nibbs RJ;Salcedo TW;Campbell JD;Yao XT;Li Y;Nardelli B;Olsen HS;Morris TS;Proudfoot AE;Patel VP;Graham GJ J Immunol. 2000 Feb 1;164(3):1488-97.
Allergic reactions are characterized by the infiltration of tissues by activated eosinophils, Th2 lymphocytes, and basophils. The beta-chemokine receptor CCR3, which recognizes the ligands eotaxin, eotaxin-2, monocyte chemotactic protein (MCP) 3, MCP4, and RANTES, plays a central role in this process, and antagonists to this receptor could have potential therapeutic use in the treatment of allergy. We describe here a potent and specific CCR3 antagonist, called Met-chemokine beta 7 (Ckbeta7), that prevents signaling through this receptor and, at concentrations as low as 1 nM, can block eosinophil chemotaxis induced by the most potent CCR3 ligands. Met-Ckbeta7 is a more potent CCR3 antagonist than Met- and aminooxypentane (AOP)-RANTES and, unlike these proteins, exhibits no partial agonist activity and is highly specific for CCR3. Thus, this antagonist may be of use in ameliorating leukocyte infiltration associated with allergic inflammation.
3.Amino acid profiles of young adults differ by sex, body mass index and insulin resistance.
Guevara-Cruz M;Vargas-Morales JM;Méndez-García AL;López-Barradas AM;Granados-Portillo O;Ordaz-Nava G;Rocha-Viggiano AK;Gutierrez-Leyte CA;Medina-Cerda E;Rosado JL;Morales JC;Torres N;Tovar AR;Noriega LG Nutr Metab Cardiovasc Dis. 2018 Apr;28(4):393-401. doi: 10.1016/j.numecd.2018.01.001. Epub 2018 Jan 10.
BACKGROUND AND AIMS: ;An increase in plasma branched-chain amino acids is associated with a higher risk of developing type 2 diabetes and cardiovascular diseases. However, little is known about the basal plasma amino acid concentrations in young adults. Our aim was to determine the plasma amino acid profiles of young adults and to evaluate how these profiles were modified by sex, body mass index (BMI) and insulin resistance (IR).;METHODS AND RESULTS: ;We performed a transversal study with 608 Mexican young adults aged 19.9 ± 2.4 years who were applicants to the Universidad Autónoma de San Luis Potosí. The subjects underwent a physical examination and provided a clinical history and a blood sample for biochemical, hormonal and amino acid analyses. The women had higher levels of arginine, aspartate and serine and lower levels of α-aminoadipic acid, cysteine, isoleucine, leucine, methionine, proline, tryptophan, tyrosine, urea and valine than the men.