Maximal Rates of Excretion and Synthesis of Urea in Normal and Cirrhotic Subjects

Abstract

A B S T R A C T When normal individuals eat 0.33 g protein N/kg body weight (BW)3' per day, they excrete 10-15 mg urea N/h per kg BW3'4. If they now ingest (at 0 h) 0.27 (dose A), 0.40 (dose B), 0.53 (dose C), 0.94 (dose D), or 1.33 (dose E) g protein N/kg BW3' (in the form of casein, ovalbumin, or lactalbumin), the rate of urea N excretion accelerates within 4 h. At dose C a maximal rate of urinary urea N excretion (MRUE) is reached, which averages 55 mg urea N/h per kg BW3' and which persists for 16 h. Higher doses of protein do not further accelerate urea excretion, but prolong the duration of MRUE to 28 h (after dose E). Blood urea N (BUN) rises by [7][8][9][10][11][12][13][14][15][16][17][18][19][20] mg/100 ml during the first 8 h after dose C to E, and remains stable within ±5 mg/100 ml during the ensuing 8-28 h of MRUE. Each increment of protein above dose C causes a further increment in plasma a-amino N. During infusion of free amino acids at a rate of 110 or 165 mg amino acid N/h per kg BW3' for 12 h, rate of urea excretion increases to the MRUE value produced by dose C-E of oral protein.These findings indicate that MRUE corresponds to a period of maximal rate of urea synthesis (MRUS). MRUS is greater than MRUE because one fraction of newly formed urea is hydrolyzed in the gastrointestinal tract, and another fraction may accumulate temporarily in body water during the MRUE period. Oral neomycin reduces the proportion of urea hydrolyzed in the gut to less than 20%; its extent is measured by recovery in the urine of a tracer dose of ["4C]urea injected intramuscularly during determination of MRUE. Accumulation of urea in body water is estimated from increment in BUN during the period of MRUE measurement (8-24 h after dose E of casein) and from body water

The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia.

“…associated with cirrhosis (20). The fraction of the dose taken up by the liver, excluding the two subjects with metastatic cancer, appeared to be a function of liver size: uptake (%) = 0.07 (liver area in Cm2) -1.2, r = +0.85,…”

The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic

“…Excessive lean protein consumption without adequate fat or carbohydrate causes a condition referred to as 'rabbit starvation' by early American explorers that results in nausea, diarrhea and eventual death (Speth & Spielmann, 1983). Clinically, this syndrome probably results from the finite ability of the liver to up-regulate the ratelimiting enzymes of urea synthesis, thereby culminating in hyperammonemia and hyperaminoacidemia (Rudman et al, 1973). For a foraging human, the avoidance of the physiologic effects of excessive dietary protein was an important factor in shaping their subsistence strategies (Noli & Avery, 1988;Speth & Spielmann, 1983;Speth, 1989).…”

“…Following a 7 week period living as hunter-gatherers in their traditional country in north-western Australia, these 10 diabetic, overweight Aborigines experienced either a great improvement or complete normalization of all of the major metabolic abnormalities of type 2 diabetes (O'Dea, 1984). Because the energy intake was low (1200 kcal) during the treatment period, the estimated daily protein intake (154.3 g=day) would have fallen well within the limits established by the mean maximal hepatic urea synthesis rates (Cordain et al, 2000a;Rudman et al, 1973). It is possible that the improvement in type 2 diabetic symptoms could in part be attributed to reduced caloric intake, however studies in Meat-based hunter-gatherer diets L Cordain et al which energy levels were controlled still yielded similar results (O'Dea et al, 1989;Wolfe & Giovannetti, 1991).…”

The Dangers of Fat Metabolism and PUFA: Why You Don’t Want to be a Fat Burner

“…For non-ketotic low carb dieting, this energy substrate production may account for much of the observed weight loss; the process of gluconeogenesis from amino acids costs approximately 33% of the energy obtained in the oxidation of the resulting glucose [12]. Additionally,if the saturable urea system [13] is overwhelmed by amino acid derived ammonia, symptoms of hyperammonemia, or "rabbit starvation," follow [14]. Even at a subclinical level, greater ammonia is a burden on kidney nephrons [15,16].…”