GBB, Key conversion through in biosynthesis process of L-carnitine

Published: admin | Format: 2017-02-27

What is Gamma Butyrobetaine?

Gamma-butyrobetaine (GBB) is a highly water-soluble derivative of gamma-amino butyric acid and a precursor of the amino acid L-carnitine. L-Carnitine could be formed from GBB by GBB dioxygenase or through the β-oxidation-like pathway. Just as its naturally-occurring equivalent, the compound serves as a precursor to the production and conversion of L-carnitine in the human body. L-carnitine has several functions in terms of digestion, metabolism and fat breakdown and without its conversion through GBB in the biosynthesis process, a lot of bodily functions will be compromised.

1.png 

Biosynthesis pathways of L-carnitine from GBB

 

Health benefits of using Gamma Butyrobetaine

Ø  Increasing L-carnitine level and metabolizing fat:

GBB could dramatically increase endogenous L-carnitine production, which means that GBB can give you better anabolic effect than the majority of products featuring L-Carnitine. One study conducted on infants showed plasma carnitine concentrations increased 3 fold when fed GBB[1].

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Another mice trial showed administration of GBB increased the concentration of L-carnitine in the plasma, brain, liver and kidney significantly, and decreased in long-chain fatty acids, palmitic acid and stearic acid levels in liver significantly. Administration of GBB may be more useful than that of L-carnitine itself for treatment of primary deficiency of carnitine due to a functional defect of the carnitine transporter [2]. GBB could be used with or in place of L-carnitine to increase free carnitine concentrations in muscle[3].

 

L-Carnitine is responsible for metabolizing fat. After breaking down the stored fat, it mobilizes the fatty acids into the bloodstream. L-carnitine is an essential element in the β-oxidation of long-chain fatty acids, because it helps to carry the fatty acids as acylcarnitine esters across the mitochondrial inner membrane for energy production.

 

Ø  Radical scavenger properties:

High concentration of GBB (1 mM) attenuated significantly the H2O2-induced decrease in LVDP. The results suggest that GBB in isolated rat heart decreased the development of mechanical dysfunction induced by infusion of hydrogen peroxide [4].

 

Ø  Cardioprotective activity:

The vasoprotective effect of GBB could be due to the reduction of oxidative stress in vascular wall. GBB attenuated the development of endothelial dysfunction in an experimental model of hypertension[5]. Increasing GBB levels while preserving the L-carnitine content in vascular tissues attenuated the development of endothelial dysfunction induced by a high glucose concentration[6].Gamma-butyrobetaine to rats showed elevated vasodilating activities[7].

 

Ø  Increasing NO levels:

These vasodilating activities were attributed to increases in nitric oxide concentrations in blood. GBB induced transient increases in nitric oxide (NO) concentrations in rat blood and myocardium.

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Fig. Changes in NO concentration in myocardium (A) and blood (B) after administration of mildronate (n; 120 mg/kg), GBB (o; 30 mg/kg) and GBB ester (0; 0.3 mg/kg).

Since nitric oxide has been shown to increase energy metabolism, it is herein understood by the inventors that increases in NO levels will lead to increased catabolism of fatty acids, which will increase the utilization of adipocytes leading to reduced fat content in the body[8].

 

 

Safety and dosage:

Toxicity:

Supplements formulated with Gamma Butyrobetaine can be quite beneficial for individuals of all ages. Toxicity of GBB is low.

Organism

Test Type

Route

Reported Dose (Normalized Dose)

Effect

Source

mouse

LD50

intravenous

475mg/kg (475mg/kg)


[9]

mouse

LD50

subcutaneous

7gm/kg (7000mg/kg)

Lungs, Thorax, or respiration:cyanosis  
  
 

Behavioral: convulsions or effect on seizure threshold
  
 

Behavioral: fluid intake

[10]

 

Recommended dosage:

20-30mg/day to give you equal effect of L-carnitine 1g/day



 

References:

[1] Olson AL et al, gamma-Butyrobetaine hydroxylase activity is not rate limiting for carnitine biosynthesis in the human infant, J Nutr. 1987, 117(6):1024-31.

[2] Higashi Y et al, Effect of gamma-butyrobetaine on fatty liver in juvenile visceral steatosis mice, J Pharm Pharmacol.,2001, 53(4):527-33.

[3] J. M. Benz, er al. Effects Of γ-Butyrobetaine and L-carnitine on carnitine concentrations in various muscle tissues of finishing pigs, Swine Day 2007, 187-189

[4] Akahira M, Hara A, Abiko Y. Effect of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on myocardial derangements induced by hydrogen peroxide in the isolated perfused rat heart. Fundam Clin Pharmacol. 1997,11(4):356

[5] Kalvins I, Veveris M. Latvian patent Nr. 11727

[6] Vilskersts R et al. Elevated vascular gamma-butyrobetaine levels attenuate the development of high glucose-induced endothelial dysfunction, Clin Exp Pharmacol Physiol. 2013,  40(8):518-24

[7] Sjakste N, Kleschyov J L, Baumane L, Dzintare M, Meirena D, Sjakste J, Sydow K, Munzel T, Kalvinsh I. Endothelium- and nitric oxide-dependent vasorelaxing activities of gamma-butyrobetaine esters: possible link to the antiischemic acitivites of mildronate. Eur J Pharmacol. Jul. 8, 2004; 495(1):67-73

[8] US2008279967A1

[9] Archives Internationales de Pharmacodynamie et de Therapie. 1963, 145, 233.

[10] Rotzsch W, Lorenz I, Strack E. On the toxicity of carnitine and some related substances. Biologica et Medica Germanica. 1959;3:28-36



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