Amino acids – Guidelines on Parenteral Nutrition, Chapter 4

Alpha-ketoglutarate (AKG), an endogenous intermediary metabolite in the Krebs cycle, is a molecule involved in multiple metabolic and cellular pathways. It functions as an energy donor, a precursor in the amino acid biosynthesis, a signalling molecule, as well as a regulator of epigenetic processes and cellular signalling via protein binding. AKG is an obligatory co-substrate for 2-oxoglutarate-dependent dioxygenases, which catalyse hydroxylation reactions on various types of substrates. It regulates the activity of prolyl-4 hydroxylase, which controls the biosynthesis of collagen, a component of bone tissue. AKG also affects the functioning of prolyl hydroxylases, which, in turn, influences the function of the hypoxia-inducible factor, an important transcription factor in cancer development and progression. Additionally, it affects the functioning of enzymes that influence epigenetic modifications of chromatin: ten–eleven translocation hydroxylases involved in DNA demethylation and the Jumonji C domain containing lysine demethylases, which are the major histone demethylases. Thus, it regulates gene expression. The metabolic and extrametabolic function of AKG in cells and the organism open many different fields for therapeutic interventions for treatment of diseases. This review presents the results of studies conducted with the use of AKG in states of protein deficiency and oxidative stress conditions. It also discusses current knowledge about AKG as an immunomodulatory agent and a bone anabolic factor. Additionally, the regulatory role of AKG and its structural analogues in carcinogenesis as well as the results of studies of AKG as an anticancer agent are discussed.

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Alpha-Ketoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use

Zdzisińska

Żurek

Kandefer‐Szerszeń

2016

Arch. Immunol. Ther. Exp.

162

133

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How to Increase Muscle Mass in Critically Ill Patients: Lessons Learned from Athletes and Bodybuilders

et al. 2020

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Essential Amino Acid Profile in Parenteral Nutrition Mixtures: Does It Meet Needs?

et al. 2018

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Background and Aims: The study compares the essential amino acid (EAA) composition of different parenteral nutrition (PN) mixtures with whey protein EAA profile and the theoretical daily EAA requirements (set by WHO/FAO/UNU or IAAO method). According to the individual EAA profile, the potential effect of several PN mixtures was evaluated on the skeletal muscle mass (SMM) of patients on home PN. Methods: Eight AA solutions and fifteen complete PN mixtures were considered. Twenty-nine clinically stable patients with short bowel syndrome on home total PN were retrospectively evaluated. SMM was estimated by bioelectrical impedance analysis. Results: The prescribed doses of EAA that showed a significant increase in home PN patients muscle mass were considerably greater than the theoretical ones, showing an EAA profile similar to whey protein. At the daily dose of 1 g of total AA s/kg body weight (BW), the considered PN mixtures mostly failed to improve SMM. Only prescribed doses which included more than 0.25 g/kg BW of total BCAA with at least 0.10 g/kg BW leucine, 0.08 g/kg BW isoleucine, and 0.06 g/kg BW methionine showed a significant increase in SMM. Conclusions: The theoretical daily requirement for each EAA was met by all considered PN solutions when the prescribed daily dose of total AAs was set at 1 g/kg BW. Nevertheless, our data suggest that only an increase in total BCAA, also richer in single AA leucine, isoleucine, and methionine, is associated with the maintenance and/or increase of SMM. According to these preliminary observations, we support the prescription of an EAA composition of PN mixtures close to that of whey protein for the preservation of SMM in patients on long-term total PN.

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Amino acids – Guidelines on Parenteral Nutrition, Chapter 4

Cited by 3 publications

References 52 publications

Alpha-Ketoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use

Alpha-Ketoglutarate as a Molecule with Pleiotropic Activity: Well-Known and Novel Possibilities of Therapeutic Use

How to Increase Muscle Mass in Critically Ill Patients: Lessons Learned from Athletes and Bodybuilders

Essential Amino Acid Profile in Parenteral Nutrition Mixtures: Does It Meet Needs?

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