Alanine muscle

M.p. 246-250°C (decomp.). A dipeptide present in mammalian muscle. Like anserine it contains the amino-acid -alanine which is not found in proteins. 

The P-alanyl dipeptides carnosine and anserine (A -methylcarnosine) (Figure 31-2) activate myosin ATPase, chelate copper, and enhance copper uptake. P-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle. Biosynthesis of carnosine is catalyzed by carnosine synthetase in a two-stage reaction that involves initial formation of an enzyme-bound acyl-adenylate of P-alanine and subsequent transfer of the P-alanyl moiety to L-histidine. 

Major amino acids emanating from muscle are alanine (destined mainly for gluconeogenesis in liver and forming part of the glucose-alanine cycle) and glutamine (destined mainly for the gut and kidneys). 

SERCA la denotes the Ca -ATPase of adult fast-twitch skeletal muscle with glycine at its C-terminus in the rabbit [53,58], and alanine at the C-terminus in the chicken [59,60]. The C-terminus of the lobster enzyme is apparently blocked [59]. 

FIGURE 8.8 H2S production in vascular tissues. IPS production by aorta homogenate (upper panel), cultured rat vascular smooth muscle cells (VSMCs middle panel), and intact rat aorta occurs after the addition of substrate L-cysteine (L-cys) and cofactor pyridoxal L-phosphate (PLP) for the enzyme CGL located in vascular tissue. H2S production is inhibited after the CGL. 3 cyano-L-alanine (BCA) is added. Ferric Lucina pectinata hemoglobin I (metHb) is added to confirm H2S production. The quantity of metHb-sulfide produced, determined spectrophotometrically, matched the levels of H2S detected by the PHSS (after [41]). 

Storage pathways are off degradative pathways are on. Glycogen is degraded by liver and muscle to provide glucose and energy. A A = amino acids KB = ketone bodies ALA = alanine LAC = lactate. 

Liver takes carbon and nitrogen waste from muscle (alanine), disposes of the nitrogen, and recycles the carbon into glucose. 

The alanine cycle accomplishes the same thing as the Cori cycle, except with an add-on feature (Fig. 17-11). Under conditions under which muscle is degrading protein (fasting, starvation, exhaustion), muscle must get rid of excess carbon waste (lactate and pyruvate) but also nitrogen waste from the metabolism of amino acids. Muscle (and other tissues) removes amino groups from amino acids by transamination with a 2-keto acid such as pyruvate (oxaloacetate is the other common 2-keto acid). 

Fructose-1,6-bisphosphatase deficiency, first describ ed by Baker and Winegrad in 1970, has now been reported in approximately 30 cases. It is more common in women and is inherited as an autosomal recessive disorder. Initial manifestations are not strikingly dissimilar from those of glucose-6-phosphatase deficiency. Neonatal hypoglycemia is a common presenting feature, associated with profound metabolic acidosis, irritability or coma, apneic spells, dyspnea, tachycardia, hypotonia and moderate hepatomegaly. Lactate, alanine, uric acid and ketone bodies are elevated in the blood and urine [11]. The enzyme is deficient in liver, kidney, jejunum and leukocytes. Muscle fructose-1,6-bisphosphatase activity is normal. 

Glucose produced by GNG from alanine or lactate may then be recycled to the tissues, including the muscle which provided the initial alanine and lactate. 

Glycogenolysis and glycogen synthesis P-oxidation of fatty acids transamination and deamination of amino acids Cori cycle and glucose-alanine cycle, which recycles substrates between muscle and liver. 

Muscle protein catabolism generates amino acids some of which may be oxidized within the muscle. Alanine released from muscle protein or which has been synthesized from pyruvate via transamination, passes into the blood stream and is delivered to the liver. Transamination in the liver converts alanine back into pyruvate which is in turn used to synthesise glucose the glucose is exported to tissues via the blood. This is the glucose-alanine cycle (Figure 7.11). In effect, muscle protein is sacrificed in order to maintain blood adequate glucose concentrations to sustain metabolism of red cells and the central nervous system. 

Alanine (abbreviated Ala or A) ((S)-2-aminopropanoic acid ct-aminopropionic acid) is a nonpolar, neutral, aliphatic amino acid with the formula HOOCCH(NH2)CH3 Ala plays a major role in the transport of nitrogen from skeletal muscles to the liver. 

Amino groups released by deamination reactions form ammonium ion (NH " ), which must not escape into the peripheral blood. An elevated concentration of ammonium ion in the blood, hyperammonemia, has toxic effects in the brain (cerebral edema, convulsions, coma, and death). Most tissues add excess nitrogen to the blood as glutamine. Muscle sends nitrogen to the liver as alanine and smaller quantities of other amino acids, in addition to glutamine. Figure I-17-1 summarizes the flow of nitrogen from tissues to either the liver or kidney for excretion. The reactions catalyzed by four major enzymes or classes of enzymes involved in this process are summarized in Table T17-1. 

In liver, aminotransferases ALT and AST can move the amino group from alanine arriving from muscle into aspartate, a direct donor of nitrogen into the urea cycle. 

Hormones can modify the concentration of precursors, particularly the lipolytic hormones (growth hormone, glucagon, adrenaline) and cortisol. The lipolytic hormones stimulate lipolysis in adipose tissue so that they increase glycerol release and the glycerol is then available for gluconeogenesis. Cortisol increases protein degradation in muscle, which increases the release of amino acids (especially glutamine and alanine) from muscle (Chapter 18). 

In muscle, the concentrations of alanine, aspartate, glutamate, glutamine, leucine, serine and valine are high that of glutamine is the highest (c. 20mmol/L). The lowest are those of methionine, tryptophan and tyrosine. 

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