Thread: Creatine/protein synthesis - ? For Trouble

Does this make sense to you?

17a-alkylated compounds enhance creatine synthesis, but at the expense of protein synthesis. Non-alkylated compounds (like test and it's 17b-esters) only increase protein synthesis but don't boost creatine production. Basically, methylation of guanidinoacetate in the body results in creatine. Donors of the methyl group are choline and methionine. Guanidinoacetate arises from a reaction between glycine and arginine. The essential aminos methionine and arginine are needed for both normal protein synthesis and the formation of creatine. Therefore, 17a-alkyl compounds stimulate the formation of creatine at the expense of cell protein synthesis because the two precursor amino acids are not optimally available for both. That means that if you take extra creatine with you're orals, you can free up more aminos for protein synthesis and that's what you really want anyway. It also makes sense to use creatine with non-alkyl compounds too because they are only concerned with cell protein and neglect creatine synthesis. So it's basically a good idea to use creatine no matter what your on! Especially with oral only cycles to optimize the effects or with ester only cycles to add the extra dimension of creatine loading. If you're stacking a high dose oral with an ester, then creatine is probably not as important in that case.

First he says one thing, then another.. at least thats what I see in this post. If Creatine is not methionine limited. The methyl donors are derived from sam-e and other donors. This posts author has his chemistry a bit mistated.

See here:

Is it time to reevaluate methyl balance in humans?

Lori M Stead, John T Brosnan, Margaret E Brosnan, Dennis E Vance and René L Jacobs. American Journal of Clinical Nutrition, Vol. 83, No. 1, 5-10, January 2006. Full paper here.

S-Adenosylmethionine (AdoMet) is the major biological methyl donor. AdoMet's methyl group arises both from the diet (eg, methionine, choline, and betaine) and from de novo synthesis by the process of methylneogenesis.

At least 50 AdoMet-dependent methylation reactions have been identified in mammals, and genomic analyses suggest that the final number will be much higher. Such methylation reactions play major roles in biosynthesis, regulation, and detoxification. Creatine synthesis is thought to account for the use of >70% of AdoMet-derived methyl groups in humans. This is not consistent with recent studies in mice, in which the phosphatidylethanolamine methyltransferase gene was deleted (PEMT–/–). Loss of this hepatic enzyme resulted in a 50% decrease in plasma homocysteine, which suggests that it accounts for a major component of whole-body AdoMet utilization.

A reexamination of human creatine metabolism showed that dietary creatine can account for as much as 50% of daily creatine requirements in nonvegetarians and, therefore, that estimates of creatine synthesis need to be reduced. We suggest that creatine synthesis is responsible for a smaller proportion of AdoMet-derived methyl groups than has been suggested and that phosphatidylcholine synthesis via phosphatidylethanolamine methyltransferase is a major consumer of these methyl groups.


From the papers interesting conclusions, Discussion Section:

The rate of AdoMet formation that was estimated by MacCoss et al (17) and the calculations we described above have several implications. We argued that the PEMT reaction may play an important role in determining methylation demand in humans (46). We also argued that creatine synthesis may not be the major consumer of methyl groups. Finally, our calculations suggest that the homocysteine remethylation pathway may be substantially more active than previously thought, considering that the rate of AdoMet formation described by MacCoss et al (17) necessitates a much higher level of methylneogenesis for a given level of methionine intake.

Clearly, the arguments advanced here are the result of estimates, first approximations, and direct evidence from animal models. In their classic study of methyl balance, Mudd et al (8) noted that their estimates may need to be modified as more information became available. It is in this spirit that we make our arguments. It is our hope that this article will generate a discussion on labile methyl balance in humans, because debate on the matter has been largely lacking in recent years.

In addition to the dietary intakes of methionine and creatine, we suggest that dietary betaine may need to be factored into the dietary sources of labile methyl groups. Certainly, clarification of the role of betaine in methyl balance is needed.

Craig (47) reported that dietary intake of betaine ranged from 1–2.5 g/d, which amounts to between 8.5 and 25 mmol labile methyl groups/d. Administration of betaine lowered plasma homocysteine in homocystinuric patients (48). Yet, Davis et al (49), using a dual tracer procedure to simultaneously measure total and folate-dependent homocysteine remethylation, found that serine, which feeds one carbon unit into the folate pool, contributed 100% of the methyl groups required for remethylation. It is clear that we must find innovative methodologies by which the questions we raised and others relating to methyl balance may be addressed in humans.

Best bet: use judicious (meaning just enough, not large doses) of various methyl donors, such as:

sam-e and methionine
TMG (betaine anhydrous)
choline and inositol
methyl-B12

Also use taurine, B6, selenium (always taken with Vit E), zinc and vitamin C, omega-3 fats - as they play important roles in regulation of the methylation/tetrahydrofolate pathways.

Creatine is synthesis is carried out via methyltransferase enzymes (2 of them).

Now, both estrogen and testosterone are implicated in the metabolism of creatine. In skeletal muscle cells, testosterone and steroid analogs of test induce increased release of creatine kinase (the breakdown of phosphocreatine for energy release). Estrogen is implicated in the synthesis of creatine kinase in recent gene studies of the pituitary, as one of many genes jointly regulated by GnR (gondadotropin releasing hormone) and esterogen.

Androgen receptor, and anabolic protein factor signals, like IGF-1, have been shown to play a role in initiating glycogen and creatine storage.

The author of this paragraph may have specific references I haven't seen that suggest altered regulation of creatine synthesis by 17a-alkylated steroids.