Re: [abmd] 3-methylhistidine?

[Guest guest]

,

This is right in the center of what I'm studying right

now. 3-methylhistidine being elevated is used in the literature very

consistently as a marker for myofibrillar degeneration, which is a fancy

name for breaking down your muscle (or basically borrowing from it) to get

at the nutrients there, whenever the body recognizes that the supply is

inadequate. This is seen in cachectic conditions, when diet no longer is

able to forestall this process, or recover from it. All of us borrow from

muscle in what they call the post-absorptive phase, or when food is not

being eaten, like in the nighttime. But usually, the body builds back that

muscle when nutritional supply recovers. They've tried using glutamine and

other amino acids to stop the processof muscle catabolism but it doesn't

work well, as an article below stated.

First, though, I'll put an article below which describes the process most

succinctly.

HIV is another condition in which you find deficiency of sulfur due to

sulfate wasting. I've put an article below showing that responsiveness to

growth hormone is reduced in this population once muscle wasting has gotten

in full swing. Despite IGF-1 levels increasing fourfold, muscle synthesis

could not occur normally. IGF-1 increases sulfate incorporation, but can't

do that if sulfate is low. Really, all the growth factors use or regulate

sulfate in one way or another. TNF alpha is also elevated in this

condition, and Dr. Waring found that TNF impairs the pathway that makes

sulfate out of cysteine.

The issue no one has properly investigated is the connection with the

sulfur chemistry.

Biosci Biotechnol Biochem 1996 Mar;60(3):501-2

Plasma N tau-methylhistidine concentration is a sensitive index of myofibrillar

protein degradation during starvation in rats.

Nagasawa T, Yoshizawa F, Nishizawa N.

Department of Bioscience and Technology, Iwate University, Japan.

Urinary excretion of N tau-methylhistidine (MeHis) in rats was linearly

elevated

by starvation for 2 days. Plasma concentration of MeHis on day 1 and day 2 of

starvation were increased 2.4- and 2.6-fold, respectively. The amount of

released MeHis from the isolated muscles into medium during a 2-h incubation

period was increased with starvation corresponded to the plasma MeHis

concentration. The results of this study suggest that plasma MeHis is a

sensitive index of myofibrillar protein degradation.

PMID: 8901113 [PubMed - indexed for MEDLINE]

51: Am J Physiol 1996 Oct;271(4 Pt 1):E718-24

Effects of amino acids on synthesis and degradation of skeletal muscle proteins

in humans.

Svanberg E, Moller-Loswick AC, s DE, Korner U, Andersson M, Lundholm K.

Department of Surgery, Sahlgrenska University Hospital, University of Goteborg,

Sweden.

Synthesis and degradation of globular and myofibrillar proteins across arm and

leg muscles were examined during stepwise increased intravenous infusion of

amino acids (0.1, 0.2, 0.4, and 0.8 g N.kg-1.day-1) to healthy volunteers.

Protein dynamics were measured by a primed constant infusion of

L-[ring-2H5]phenylalanine and the release of 3-methylhistidine from skeletal

muscles. Arterial concentrations and flux of glucose, lactate, and free fatty

acids were unchanged despite increasing concentrations of plasma amino acids

from 2.6 to 5.7 mM. Plasma insulin, insulin-like growth factor I (IGF-I), and

plasma concentrations of IGF-I-binding proteins-1 and -3 remained at fasting

levels throughout the investigation. Amino acid infusion caused a significant

uptake of the majority of amino acids across arm and leg tissues, except

tyrosine, tryptophan, and cysteine, probably due to low concentrations of these

amino acids in the formulation. The balance of globular proteins improved

significantly (P & lt; 0.01) due to stimulation of synthesis and attenuation of

degradation across arm and leg tissues, despite insignificant uptake of

tyrosine, tryptophan, and cysteine. Degradation of myofibrillar proteins was

uninfluenced by provision of amino acids. The results demonstrate that neither

insulin nor circulating IGF-I explained improved protein balance in skeletal

muscles after elevation of plasma amino acids. Rather, some amino acids in

themselves trigger cellular reactions that initiate peptide formation. Limited

availability of some extracellular amino acids was overcome by increased

reutilization of the intracellular amino acid.

PMID: 8897860 [PubMed - indexed for MEDLINE]

Am J Physiol 1996 Oct;271(4 Pt 1):E718-24

Effects of amino acids on synthesis and degradation of skeletal muscle proteins

in humans.

Svanberg E, Moller-Loswick AC, s DE, Korner U, Andersson M, Lundholm K.

Department of Surgery, Sahlgrenska University Hospital, University of Goteborg,

Sweden.

Synthesis and degradation of globular and myofibrillar proteins across arm and

leg muscles were examined during stepwise increased intravenous infusion of

amino acids (0.1, 0.2, 0.4, and 0.8 g N.kg-1.day-1) to healthy volunteers.

Protein dynamics were measured by a primed constant infusion of

L-[ring-2H5]phenylalanine and the release of 3-methylhistidine from skeletal

muscles. Arterial concentrations and flux of glucose, lactate, and free fatty

acids were unchanged despite increasing concentrations of plasma amino acids

from 2.6 to 5.7 mM. Plasma insulin, insulin-like growth factor I (IGF-I), and

plasma concentrations of IGF-I-binding proteins-1 and -3 remained at fasting

levels throughout the investigation. Amino acid infusion caused a significant

uptake of the majority of amino acids across arm and leg tissues, except

tyrosine, tryptophan, and cysteine, probably due to low concentrations of these

amino acids in the formulation. The balance of globular proteins improved

significantly (P & lt; 0.01) due to stimulation of synthesis and attenuation of

degradation across arm and leg tissues, despite insignificant uptake of

tyrosine, tryptophan, and cysteine. Degradation of myofibrillar proteins was

uninfluenced by provision of amino acids. The results demonstrate that neither

insulin nor circulating IGF-I explained improved protein balance in skeletal

muscles after elevation of plasma amino acids. Rather, some amino acids in

themselves trigger cellular reactions that initiate peptide formation. Limited

availability of some extracellular amino acids was overcome by increased

reutilization of the intracellular amino acid.

PMID: 8897860 [PubMed - indexed for MEDLINE]

42: J Clin Invest 1997 Oct 15;100(8):2125-32

Responsiveness of muscle protein synthesis to growth hormone administration in

HIV-infected individuals declines with severity of disease.

McNurlan MA, Garlick PJ, Steigbigel RT, DeCristofaro KA, Frost RA, Lang CH,

RW, Santasier AM, Cabahug CJ, Fuhrer J, Gelato MC.

Department of Surgery, State University of New York at Stony Brook, Stony

Brook,

New York 11794, USA. mcnurlan@...

This study was undertaken to determine if human recombinant growth hormone

(hrGH, 6 mg/d for 2 wk) would stimulate muscle protein synthesis in AIDS

wasting. Healthy controls were compared with patients who were HIV+, had AIDS

without weight loss, and had AIDS with & gt; 10% weight loss. Before hrGH,

rates of

skeletal muscle protein synthesis, measured with l-[2H5]phenylalanine, were the

same in controls and in all stages of disease. Rates of myofibrillar protein

degradation, however, assessed from urinary excretion of 3-methyl histidine,

were higher in AIDS and AIDS wasting than in HIV+ or healthy individuals. The

group with weight loss had significantly higher TNFalpha levels but not higher

HIV viral loads. Muscle function, as determined by isokinetic knee

extension and

shoulder flexion, was significantly higher in controls than all infected

individuals. After GH, rates of protein synthesis were stimulated 27% in

controls, with a smaller increase (11%) in HIV+, and a significant depression

(42%) in AIDS with weight loss, despite fourfold elevation in insulin-like

growth factor-I in all groups. There was a significant correlation of

hrGH-induced changes in muscle protein synthesis with severity of disease (P =

0.002). The results indicate increased basal muscle protein degradation and

decreased responsiveness of muscle protein synthesis to GH in the later stages

of disease.

Publication Types:

Clinical Trial

Controlled Clinical Trial

PMID: 9329979 [PubMed - indexed for MEDLINE]

At 05:24 AM 11/28/2001 +0000, you wrote:

>Does anyone know what a high level of 3-methylhistidine in a plasma

>amino acid test would indicate?

>

>Thanks,

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