BCAAs

BCAA branched-chain amino acids DHA docosahexenoic acid... 

Survivors may suffer a metabolic relapse at any time. The most common cause of relapse is intercurrent infection, which favors endogenous protein catabolism. As a consequence, the patient s limited capacity to oxidize BCAAs is overwhelmed and these compounds, together with their cognate ketoacids, accumulate to a toxic level. Relapse also can occur in association with surgery, trauma and emotional upset. 

Patients with partial enzymatic deficiencies may present later in life with intermittent ketoacidosis, prostration and recurrent ataxia. The plasma concentrations of BCAA are elevated during these episodes but they maybe normal or near-normal during the periods when patients are metabolically compensated. 

Effective treatment of maple syrup urine disease involves the restriction of dietary branched-chain amino acids. Long-term treatment entails the dietary restriction of the BCAAs. This is accomplished by administration of a special formula from which these amino acids are removed. The outlook for intellectual development is favorable in youngsters in whom diagnosis is made early and who do not suffer recurrent, severe episodes of metabolic decompensation [17]. 

The oxoacids produced as a result of transamination of the BCAAs are either oxidised in the muscle, or, in resting muscle, released into the blood for uptake and oxidation in the liver (Figure 8.17, see also Figure 8.23). 

Central administration of dipeptides, beta-alanyl-BCAAs, induces hyperactivity in chicks. BMC Neurosci. 8, 37—42. 

FIGURE 5.4 The VB structures for singlet and triplet states of C3H3, along with the graphical representation of their interaction matrix elements. The spread of the states is easily predicted from the circle mnemonic used in simple Hiickel theory. The expressions for the YB structures (dropping normalization) are deduced from each other by circular permutations tj = abcc — abcc, 1(I>2 = bcaa — bcaa, 1(I>3 = cabb — cabb, 34>j = abcc, 34>2 = hcaa, 34>3 = cabb. ... 

The liver plays a central role in the synthesis of nearly all circulating proteins. Plasma contains 60-80 g/L of protein and this is turned over at a rate of approximately 250 g/day. A variety of proteins are constructed in the liver using amino acids (Aa) as their basic building blocks. Amino acids are categorised as essential and non-essential , the former being a requirement of dietary intake as they cannot be constructed in vivo, whereas the latter can be synthesised hepatically. The essential amino acids are further categorised as branched-chain amino acids (BCAA leucine, valine, isoleucine) or aromatic amino acids (AAA phenylalanine, tyrosine, methionine) according to their structure. Table... 

Normal/reduced plasma concentration of BCAA muscle are relatively low in concentration as muscle metabolism continues normally. Aromatic amino acids which are metabolised hepatically are present in relatively high concentrations as the deranged liver is unable to perform its usual metabolic functions encephalopathy... 

Amino acids essential semi-essen- non-essen- BCAA AAA polar ketogenic glucogenic... 

Tab. 3.6 Classification of the 20 important (essential and non-essential) amino acids (AA = amino acid BCAA = branched-chain amino acid AAA = aromatic amino acid)...

Fig. 15.1 Branched-chain amino acid cycle and glutamate cycle in the brain (A = astrozyte, N = neuron, BBB = blood-brain barrier, GNT = glutamate neurotransmitter, BCAA = branched-chain amino acids, BCKA = branched-chain keto acids) (150)...

The application of branched-chain amino acids (BCAA) was based on the therapeutic target of compensating for the surplus of aromatic amino acids in order to suppress the synthesis of false neurotransmitters. Nevertheless, up to now, (7.) no correlation has been found between the amino acid imbalance in the plasma and the degree of severity of HE, (2.) no temporal correlation has been established between the normalization of the amino acid imbalance and the improvement of HE, and (3.) no influence has been detected on normal neurotransmitters in the CSF. These three counterarguments are, however, the subject of controversy and critical discussion. 

The undoubtedly genuine efficacy of branched-chain amino acids cannot be explained merely by the improved metabolism of ammonia, but also by their complex influences on the metabolism of the muscles, liver and brain. The wide range of results may be the outcome of applying various test parameters as well as using different, possibly even unfavourable additives (xylitol, sorbitol, fructose, fats, etc.) Some 18 studies have been evaluated, but an ultimate assessment of the elEcacy of BCAA on HE has not yet been achieved. (124)... 

A daily dosage of 0.3 g/kg BW is recommended (approx. 3 X 10 g). The use of BCAA has become established for latent and manifest HE. It has even been possible to render patients fit to drive again. No side effects are known. The efficacy of branched-chain amino acids as parenteral i.v. therapy is well validated for the severe stages II—IV of HE. The concomitant intake of arginine and ornithine aspartate has proved to be particularly effective. (127) Eatty emulsions are to be avoided since they release tryptophan from the albumin binding and inhibit the utilization of branched-chain amino acids in the musculature. (123, 126, 129, 131, 133, 138, 140, 145, 148-151, 170) (s. p. 860)... 

Merli, M., Riggio, O., Pieche, U., Ariosto, F., Pinto, G., Romiti, A., Varride, M., Capocaccia, L. The effect of oral BCAA supplement on diurnal variations in plasma amino acid concentrations in cirrhotic patients. Nutrition 1988 4 351 -356... 

Campollo, O., Sprengers, D., McIntyre, N. The BCAA/AAA ratio of plasma amino acids in three different groups of cirrhotics. Rev. Invest. Clin. 1992 44 513-518... 

The cirrhosis patient is in a vicious circle regarding protein metabolism cirrhosis hepatic encephalopathy protein restriction malnutrition catabolism Thus, prolonged protein restriction and catabolism may considerably worsen the prognosis of cirrhosis. In this hazardous situation, the dietary and therapeutic use of branched-chain amino acids (BCAA), i.e. valine, leucine and isoleucine, is a logical therapeutic intervention. 

Branched-chain amino acids apparently stimulate the urea cycle. Carbamoylphosphate synthetase, which channels ammonia into the urea cycle, is induced by ornithine and N-acetylglutamate as a cofactor of urea synthesis. Here, BCAA follow two modes of action (i.) they stimulate the synthesis of N-acetylglutamate via synthetase formed from glutamate and acetyl CoA, and (2.) they inhibit omithine-keto acid transferase, which is the enzyme responsible for ornithine degradation, leading to an increase in ornithine concentration. Ammonia detoxication is thus stimuiated by two regu-iatory mechanisms, (s. fig. 40.2)... 

As a rule, cirrhosis patients show reduced plasma BCAA levels and unchanged BCAA concentrations in the brain, whereas methionine and aromatic amino acids (AAA) (phenylalanine, tyrosine, tryptophan) are elevated in the plasma and brain, (s. p. 280) The fall in BCAA ieveis is attributable to its increased degradation, which, in turn, is caused or aggravated by hyperinsulinaemia. 

The indication for administering BCAA in patients with hepatic encephalopathy to compensate amino-acid imbalance was proposed by J.E. Fischer et al. in 1974, and implemented parenterally. However, oral application of BCAA for an adequate treatment period also has beneficial effects on cirrhosis and HE (7.) improvement in protein tolerance and the nutritional condition, (2.) improvement in cerebral functions (II8, 122), probably due to an amelioration of liver function, (2.) stimulation of ammonia detoxification with a positive nitrogen balance (118), (4.) reduction in or normalization of AAA levels, and (5.) promotion of glutamine synthesis with a favourable effect on the cells of the immune system and on renal function. By means of BCAA, it was possible to prolong the survival time and delay the occurrence of liver failure in rats with CC -induced cirrhosis. (123, 126) However, there are diverging results, which need further clarification. In principle, the use of BCAA is considered to be a necessary form of supplementary treatment for catabolic metabolism in cirrhosis (124,125, 127, 128, 130-132), in (also latent) HE and after curative resection of hepatocellular carcinoma. (I2l) (s. p. 280)... 

Isoleucine, valine, and leucine are the branched-chain amino adds (BCAAs). They are indispensable (essential), but the risk of developing a dietary deficiency is low because they are plentiful in most diets. The branched-chain amino adds. In addition to phenylalanine, are the most lipophilic of the amino acids ... 

Net breakdown of muscle can occur with either exercise or prolonged fasting. The mechanisms that control the breakdown of the various types of protein found in muscle are not well understood. It has, however, been established that while the branched-chain amino acids (BCAAs) released tend to be oxidized for energy in the muscle cell, other released amino acids enter the bloodstream for catabolism, and perhaps gluconeogenesis, in the liver Examination of the amino acids released from skeletal muscle reveals an apparent anomaly alanine accounts for or ly about 6% of the amino acids of muscle, but for about 35% of the amino acids released from muscle during exerdse. 

FIGURE 439 First step in catabolism of BCAAs and iramfer of a-amino groups to pyruvate. 

Carnitine is required for transport of longoxidative metabolism as well as in the formation of ketone bcidies, The concentration of free carnitine in muscle is about 4,0 mmol/kg. The concentration of carnitine bound to long-chain fatty adds (fatty acyl-camitine) is lower, about 0,2 mmol/kg. Short-chain fatty adds, including acetic, are also esterified to carnitine, but the functions of these complexes are not clear. There is some indication that keto forms of BCAAs (BCKAs) can also be esterified to carnitine. These complexes can then be transported into the mitochondria for complete oxidation of the BCKAs, The importance of this mode of BCKA transport is not dear (Takakura et ai., 1997). 

The branched-chain amino adds (BCAAs) are leucine, isoleucLne, and valine. Pathways for the breakdown cif leucine and isoleudnc appear in Figures 8,5 and... 

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