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Matthews' Group Research

Matthews' research in nutrition

Description of Research in Metabolism and Nutrition:

Our research has used stable isotopically labeled tracers and kinetic models to measure rates and flows of individual metabolites in vivo in the human body.  These kinetic data are then used to define human physiology and relate physiology to nutritional needs of humans.

Over the past two decades we have developed a variety tracer methods for measuring most of the amino acids and their metabolism in the body.

  One of the earliest and most widely applied methods we have developed was the use of [1-13C]leucine and similar essential amino acid tracers to follow in vivo rates of whole body protein breakdown, oxidation, and uptake of amino acids for protein synthesis.  Most of this early work was performed at Washington University School of Medicine in St. Louis with Dennis Bier, M.D. and with Vernon Young, Ph.D. at MIT in Boston.

Photo of DE Matthews

Photo from Sept. 2001

A second area of research to understand how specific hormones regulate and alter amino acid and protein metabolism.  Protein is absolutely critical for life.  It forms the basis of skeletal muscle that provides the structure for our mobility, our ability to breath and our ability to pump blood through the heart.  Protein is the heart of our immune function and the heart of all enzymes that make it possible for all of the chemistry of life to occur.  When people die of starvation, they generally do not die of lack of fuel, but of a loss of protein.  Lose much more than 25% of your protein, and the critical functions of life will cease.  The body regulates and conserves protein stores to maintain protein mass as best as possible.  Yet in injury and stress, the body uses protein for energy at an accelerated rate.  We have been studying how individual hormones contribute to this process and have addressed control of protein metabolism by individual hormones.

A third area of research involves understanding the digestion and distribution of individual amino acids.  Protein cannot be made unless all 20 amino acids are present in appropriate amounts.  If any amino acid is lacking, protein synthesis will be impaired.  In addition, amino acids play key roles as precursors for a variety of other compounds and factors in the body.  The least understood area of metabolism is the metabolism of the nonessential amino acids. Because these amino acids can be produced in the body, they are not essential to our diet. However, that does not mean they are not important.  These amino acids have numerous pathways of importance in the body, yet we have a poor understanding of which pathways are prominent or how these pathways are regulated in specific organs.  We have been studying how key nonessential amino acids are metabolized by the gut and liver when given in the diet.

A fourth area of research involves the regulation of protein stores, specifically skeletal muscle metabolism.  Besides being the largest reservoir of protein in the body, muscle protein is critical to our mobility.  A lack of muscle protein means a lack of strength and increased disability.  We know that people lose muscle mass and strength with advancing age.  We know that women lose muscle mass faster after menopause, but we do not understand why these losses occur.  We are applying methods of stable isotopes to measure directly the rate of synthesis of muscle protein.  We are interested in understanding both what happens to the synthesis of muscle as women go through menopause and how we can best maintain synthesis of muscle protein in postmenopausal women.

Work in Metabolism and Nutrition:

Recent textbook chapters:

  • DE Matthews: Proteins and amino acids. In: Modern Nutrition in Health and Disease, ME Shils, M Shike, JA Olson, AC Ross, B Caballero & RJ Cousins, eds. Philadelphia: Lippincott, Williams & Wilkins, 2006, 23-60.
  • DE Matthews: Stable isotopes to measure in vivo metabolism and kinetics. In: The Encyclopedia of Mass Spectrometry, Volume 3: Biology Applications, ML Gross & RM Caprioli, eds. Oxford, England: Elsevier, 2006, 347-356

Papers on splanchnic bed (gut & liver) metabolism of dietary amino acids using stable isotopes:

  • A Battezzati, DJ Brillon & DE Matthews: Oxidation of glutamic acid by the splanchnic bed in humans. Am. J. Physiol. 269: E269-E276, 1995.
  • A Battezzati, M Haisch, DJ Brillon & DE Matthews: Splanchnic utilization of enteral alanine in humans. Metabolism 48: 915-921, 1999.
  • DE Matthews, R Harkin, A Battezzati & DJ Brillon: Splanchnic bed utilization of enteral a-ketoisocaproate in humans. Metabolism 48: 1555-1563, 1999.
  • M Haisch, NK Fukagawa & DE Matthews: Oxidation of glutamine by the splanchnic bed in humans. Am. J. Physiol. 278: E593-E602, 2000.

Protocol for Measuring 1st-Pass Absorption of Enteral Tracers

IVNG figure

Papers on amino acid metabolism:

  • MJ MacCoss, NK Fukagawa & DE Matthews: Measurement of intracellular sulfur amino acid metabolism in humans. Am. J.Physiol. Endocrinol. Metab. 280: E947-E955, 2001.
    Homocysteine exists in plasma as a free amino acid and bound to other thiol-containing compounds by disulfide bonds.   We measure total 13C-homocysteine enrichment in plasma and, therefore, may underestimate intracellular homocysteine enrichment if the exchange between the plasma free and bound forms of homocysteine is slow.  Because cystathionine in plasma can only be produced from the transsulfuration (TS) of homocysteine inside cells, plasma 13C-cystathionine enrichment should reflect 13C-homocysteine enrichment if the equilibration of 13C-homocysteine is rapid and within the time frame of the infusion.

The process of equilibration of intracellular 13C-homocysteine with total homocysteine in blood

AJPE 20001 Hcy Fig 4
   The data were fitted to a single exponential curve of the form E = Ef(1-e -kt) where E is the plasma enrichment (mpe) at time t (h), Ef is the fitted value for the enrichment (mpe) at infinity and k is the fitted rate constant (h-1).
   The fitted curves were
   E = 6.21±0.14 (1-e-(0.40±0.03)t) for 13C-homocysteine (r2 = 0.967) and
   E = 6.03±0.28 (1-e-(0.49±0.09)t) for 13C-cystathionine (r2 = 0.85).
  The broken line is the 13C-cystathionine fit and the solid line is the 13C-homocysteine fit.  Data are the mean±SE for N=8 subjects.

The time course of plasma [1-13C]homocysteine & [1-13C]cystathionine during infusion of [1-13C]methionine and [methyl-2H3]methionine.

AJPE 2001 Hcy Fig 3
    

These data demonstrate that

   1. The rate of equilibration of bound and free homocysteine in blood is equal to or faster than intracellular equilibration.
   2. The slow rise to plateau in plasma 13C-homocysteine is due to slow equilibration of intracellular methionine pools.
  • MJ Toth, MJ MacCoss, ET Poehlman & DE Matthews: Recovery of 13CO2 from infused [1-13C]leucine and [1,2-13C2]leucine in healthy humans. Am. J. Physiol. Endocrinol. Metab. 281: E233-E241, 2001.

Last modified May 12 2009 02:32 PM

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