Basic metabolism: proteins

Proteins serve a range of physiological functions in health and in disease. Their overall structure is determined predominantly by the sequence of amino acids when they are synthesized, which in turn is a derivative of the sequence of nucleotides in the corresponding segment of DNA. There is a constant turnover of body protein, the rate of which exceeds dietary protein intake and therefore suggests a degree of recycling. Some amino acids that enter the body protein pool can be synthesized (‘non-essential’ amino acids) while others can only be obtained through dietary means (‘essential’ amino acids). During critical illness and significant trauma there appears to be dysregulation such that synthesis of some non-essential amino acids is limited, while there is an increase in amino acid oxidation. Modification of dietary intake to address the potential imbalance in illness is probably insufficient in isolation to prevent muscle wasting.     

Basic metabolism: proteins

Proteins serve a range of physiological functions in health and in disease. Their overall structure is determined predominantly by the sequence of amino acids when they are synthesized, which in turn is a derivative of the sequence of nucleotides in the corresponding segment of DNA. There is a constant turnover of body protein, the rate of which exceeds dietary protein intake and therefore suggests a degree of recycling. Some amino acids that enter the body protein pool can be synthesized (‘non-essential’ amino acids) while others can only be obtained through dietary means (‘essential’ amino acids). During critical illness and significant trauma there appears to be dysregulation such that synthesis of some non-essential amino acids is limited, while there is an increase in amino acid oxidation. Modification of dietary intake to address the potential imbalance in illness is probably insufficient in isolation to prevent muscle wasting.     

Urea index and nitrogen balance in uremic patients on miminal nitrogen intakes.

Normal anduremic subjects were studied on different protein intakes. The uremic patients were also given minimal amounts of nitrogen in the form of 8 essential amino acids, with or without the addition of histidine. It was noticed that as little as 416 mg of essential amino acid nitrogen was sufficient to cover body needs if enough non-essential nitrogen was present. It was also demonstrated that on low-nitrogen intakes, the ratio of urinary urea to total urinary nitrogen varied with nitrogen balance.     

Intermediary metabolism

Carbohydrate and fat form the immediate and long-term energy stores of the body. Protein constitutes the active (functional) cell mass and is also an energy source but, normally, a relatively minor one. All three macronutrients are interrelated. Proteins are synthesized from amino acids derived from ingested protein. Glucose and fat provide energy via adenosine triphosphate. The brain and red blood cells can only obtain their energy from glucose. Glucose is oxidized via the glycolytic and the tricarboxylic acid (Krebs) cycle pathways. Fatty acids are metabolized by the process of β-oxidation, whereby two carbon fragments are cleaved from the fatty acid chain and enter the Krebs cycle. Amino acids are deaminated to keto acids and the nitrogen moiety excreted in the urine mostly as urea. The keto acids enter the metabolic pathways at various points, mostly in the Krebs cycle. Glucose can be synthesized from lactate, glycerol and amino acids (gluconeogenesis), but not from fatty acids.     

Intermediary metabolism

Carbohydrate and fat form the immediate and long-term energy stores of the body. Protein constitutes the active (functional) cell mass and is also an energy source but, normally, a relatively minor one. All three macronutrients are interrelated. Proteins are synthesized from amino acids derived from ingested protein. Glucose and fat provide energy via adenosine triphosphate. The brain and red blood cells can only obtain their energy from glucose. Glucose is oxidized via the glycolytic and the tricarboxylic acid (Krebs) cycle pathways. Fatty acids are metabolized by the process of β-oxidation, whereby two carbon fragments are cleaved from the fatty acid chain and enter the Krebs cycle. Amino acids are deaminated to keto acids and the nitrogen moiety excreted in the urine mostly as urea. The keto acids enter the metabolic pathways at various points, mostly in the Krebs cycle. Glucose can be synthesized from lactate, glycerol and amino acids (gluconeogenesis), but not from fatty acids.     

Oral essential amino acid supplementation in patients on maintenance hemodialysis

Sixteen patients with chronic renal failure on maintenance hemodialysis were studied before and during oral treatment with essential amino acids. The patients received their usual diets (60-100 g protein/day) throughout the study. Plasma amino acids were studied pre-dialysis before supplements were started, after one month and after three months treatment; some measurements were also carried out post-dialysis. Before treatment 63% of patients pre-dialysis, and 82% post dialysis, had at least one essential amino acid value which was lower than our normal range. After one month of treatment 38% of patients pre-dialysis, and 67% post-dialysis, had one or more low essential amino acid value. After 3 months only 2 patients had an abnormal essential amino acid chromatogram pre-dialysis. Changes in non-essential amino acids, blood urea, serum proteins and hemoglobin are also reported. The data show that low plasma essential amino acid concentrations are frequently present in patients on maintenance hemodialysis even when the diet contains theoretically adequate amounts of protein. This deficiency can be corrected successfully with oral essential amino acid supplements.     

Macronutrients,minerals, vitamins and energy

Carbohydrates have the general formula C_n(H₂O)_n. Monosaccharides have between three and six carbon atoms and exist as chains or ring structures. As rings, they link with other monosaccharide rings. The major carbohydrate in humans is glucose, which is stored as glycogen: branching chains of glucose molecules. Fat (triglyceride), which makes up adipose tissue, consists of three fatty acids bonded to glycerol, but other lipids include phospholipids and steroids. Proteins are composed of chains of amino acids linked by amide bonds folded on each other to form protein structures. Vitamins and minerals are obtained from the diet and are required in varying quantities for a variety of metabolic processes. Energy is derived from the oxidation of carbohydrate, fat and protein. Energy expenditure and substrate oxidation can be calculated from oxygen consumption, carbon dioxide production and urinary nitrogen excretion.     

Macronutrients,minerals, vitamins and energy

Carbohydrates have the general formula C_n(H₂O)_n. Monosaccharides have between three and six carbon atoms and exist as chains or ring structures. As rings, they link with other monosaccharide rings. The major carbohydrate in humans is glucose, which is stored as glycogen: branching chains of glucose molecules. Fat (triglyceride), which makes up adipose tissue, consists of three fatty acids bonded to glycerol, but other lipids include phospholipids and steroids. Proteins are composed of chains of amino acids linked by amide bonds folded on each other to form protein structures. Vitamins and minerals are obtained from the diet and are required in varying quantities for a variety of metabolic processes. Energy is derived from the oxidation of carbohydrate, fat and protein. Energy expenditure and substrate oxidation can be calculated from oxygen consumption, carbon dioxide production and urinary nitrogen excretion.     

Protein metabolism in uraemia.

Protein metabolism in uraemia is reviewed. Very few, if any, disorders of amino acid metabolism can at present confidently be attributed to uraemia per se rather than to protein/energy deprivation. Retained urea nitrogen is recycled to the liver as ammonia; a proportion is reutilized for synthesis of non-essential amino acids and, if their carbon skeletons are supplied, for synthesis of essential amino acids. Practical applications of the reutilization of non-amino nitrogen in advanced chronic renal failure are being explored. Nevertheless, uraemic individuals readily become undernourished, and they should receive as much protein as their symptoms will permit.     

Intermediary metabolism

Carbohydrate and fat form the immediate and long-term energy stores of the body, and protein constitutes the active (functional) cell mass and is also an energy source but, normally, a relatively minor one. All three macronutrients are interrelated. Proteins are synthesized from amino acids derived from ingested protein. Glucose and fat provide energy via ATP. The brain and red cells can only obtain their energy from glucose. Glucose is oxidized via the glycolytic and the tricarboxylic acid (Krebs) cycle pathways. Fatty acids are metabolized by the process of β-oxidation, whereby two carbon fragments are cleaved from the fatty acid chain and enter the Krebs cycle. Amino acids are deaminated to keto acids and the nitrogen moiety excreted in the urine mostly as urea. The keto acids enter the metabolic pathways at various points, mostly in the Krebs cycle. Glucose can be synthesized from lactate, glycerol and amino acids (gluconeogenesis) but not from fatty acids.     

Protein – Which is Best?

Protein intake that exceeds the recommended daily allowance is widely accepted for both endurance and power athletes. However, considering the variety of proteins that are available much less is known concerning the benefits of consuming one protein versus another. The purpose of this paper is to identify and analyze key factors in order to make responsible recommendations to both the general and athletic populations. Evaluation of a protein is fundamental in determining its appropriateness in the human diet. Proteins that are of inferior content and digestibility are important to recognize and restrict or limit in the diet. Similarly, such knowledge will provide an ability to identify proteins that provide the greatest benefit and should be consumed. The various techniques utilized to rate protein will be discussed. Traditionally, sources of dietary protein are seen as either being of animal or vegetable origin. Animal sources provide a complete source of protein (i.e. containing all essential amino acids), whereas vegetable sources generally lack one or more of the essential amino acids. Animal sources of dietary protein, despite providing a complete protein and numerous vitamins and minerals, have some health professionals concerned about the amount of saturated fat common in these foods compared to vegetable sources. The advent of processing techniques has shifted some of this attention and ignited the sports supplement marketplace with derivative products such as whey, casein and soy. Individually, these products vary in quality and applicability to certain populations. The benefits that these particular proteins possess are discussed. In addition, the impact that elevated protein consumption has on health and safety issues (i.e. bone health, renal function) are also reviewed.

Key Points

• Higher protein needs are seen in athletic populations.
• Animal proteins is an important source of protein, however potential health concerns do exist from a diet of protein consumed from primarily animal sources.
• With a proper combination of sources, vegetable proteins may provide similar benefits as protein from animal sources.
• Casein protein supplementation may provide the greatest benefit for increases in protein synthesis for a prolonged duration.

Key words: Sport supplementation, ergogenic aid, animal protein, vegetable protein     

Branched chain amino acid administration and metabolism during starvation, injury, and infection.

Branched chain amino acids were administered intragastrically in a septic-fractured rat model to determine the degree and mechanism of their protein-sparing ability. The septic injury model was first shown to produce a metabolic response characterized by hyperglycemia, reduced ketonemia and increased nitrogen loss. Branched chain amino acids were then administered either alone or as 25% or 50% (w/w) of a complete crystalline amino acid solution. L-(U-14C)-tyrosine was added to the diet to estimate protein synthesis in individual tissues. Branched chain amino acids, when given alone, spared total body nitrogen as compared with fasting by increasing the fractional synthesis of both mixed liver and muscle protein. Although the two complete amino acid mixtures produced similar nitrogen preservation and muscle synthesis in the septic animals, the crystalline amino acid diet containing 50% branched chain amino acids resulted in the greatest preservation of total liver nitrogen and the highest fractional synthetic rate. The effect of branched chain amino acids would not appear to be explained by their nitrogen content alone, and in starvation with injury and infection, increased intakes may have potential benefit. Clinical trials in starved, injured man appear to be indicated.     

The effect of amino acids,carbohydrate and fat emulsion on the metabolism in gastrectomized patients

Nitrogen balance and other metabolic activity can be maintained by adequate calorie and protein supply during immediate post-gastrectomy period. Despite high intake of protein, great loss of nitrogen seems to occur in urine during infusion with polyalcohol sugars as compared with natural sugars, e.g., glucose, fructose and maltose. The best utilization of amino acids resulting in positive nitrogen balance and energy utilization were shown to be achieved by combined use of Intralipid, glucose, maltose and essential as well as non-essential amino acids in the clinical and laboratory studies.     

Macronutrients,minerals, vitamins and energy

Carbohydrates have the general formula C_n(H₂O)_n. Monosaccharides have between three and six carbon atoms and exist as chains or ring structures. As rings, they link with other monosaccharide rings. The major carbohydrate in humans is glucose, which is stored as glycogen: branching chains of glucose molecules. Fat (triglyceride), which makes up adipose tissue, consists of three fatty acids bonded to glycerol, but other lipids include phospholipids and steroids. Proteins are composed of chains of amino acids linked by amide bonds folded on each other to form protein structures. Vitamins and minerals are obtained from the diet and are required in varying quantities for a variety of metabolic processes. Energy is derived from the oxidation of carbohydrate, fat and protein. Energy expenditure and substrate oxidation can be calculated from oxygen consumption, carbon dioxide production and urinary nitrogen excretion.     

The effect of amino acids, carbohydrate and fat emulsion on the metabolism in gastrectomized patients.

Nitrogen balance and other metabolic activity can be maintained by adequate calorie and protein supply during immediate postgastrectomy period. Despite high intake of protein, great loss of nitrogen seems to occur in urine during infusion with polyalcohol sugars as compared with natural sugars, e.g., glucose, fructose and maltose. The best utilization of amino acids resulting in positive nitrogen balance and energy utilization were shown to be achieved by combined use of Intralipid, glucose, maltose and essential as well as non-essential amino acids in the clinical and laboratory studies.     

Letter to the Editor: “Acute Renal Failure and Hypercalcaemia: Sarcoidosis May Be the Culprit”

Critically ill patients with acute renal failure are traditionally treated with low-protein diets to help control uremia. This dietary approach may be deleterious to the patient's nutritional status and unnecessary, especially if continuous renal replacement therapies (CRRT) are used. However, the optimal amount of protein supplementation during CRRT is unknown. In patients receiving CRRT, a high protein intake may result in a positive nitrogen balance in the absence of uncontrolled uremia. Accordingly, we studied nitrogen metabolism in two consecutive cohorts of acute renal failure patients receiving equal amounts of calories but variable amounts of nitrogen. One group received protein according to the preferences of the attending clinician, the other a high and fixed amount of protein (2.5 g/kg/day). Patients treated according to attending clinician preferences received significantly less dietary protein (1.2 g/kg/day vs. 2.5 g/kg/day; p < 0.0001) and had a negative mean nitrogen balance of -5.5 g/day. Patients receiving a high and fixed amount of protein had a less negative mean nitrogen balance (-1.92 g/day). Such patients were more likely to experience a positive nitrogen balance during any 24-h period (53.6% vs. 36.7%; p < 0.05). They also required more aggressive hemofiltration to maintain control of uremia (mean ultradiafiltrate volume: 2145 mL/h vs. 1658 mL/h; p < 0.0001) and had a significantly higher but still acceptable mean plasma urea level (26.6 mmol/L vs. 18 mmol/L; p < 0.0001). Survival was not significantly different in the two groups (37.5% vs. 31.3%). We conclude that a high-protein diet can be safely administered to critically ill patients with acute renal failure receiving continuous renal replacement therapy. Such a high protein intake improves nitrogen balance when compared to moderate protein intake. A low protein intake is unnecessary in patients treated with CRRT.     

胆道术后并发急性肾衰的营养治疗(附7例报告)

报告７例胆道术后并发急性肾衰（ＡＲＦ）、氮质血症病人实施肠外营养（ＰＮ）治疗的体会。全组病例均用含８种必需氨基酸（ＥＡＡ）的肾安，７％Ｖａｍｉｎ和氨复命等提供氮源，并以２０％和１０％Ｉｎｔｒａｌｉｐｉｄ及适量葡萄糖作为主要能源，按“全合一”营养混和液行ＰＮ治疗，疗效满意。作者认为：①针对不同原因ＡＲＦ的ＰＮ治疗，应供给足够能量和较最小需要量稍高的ＥＡＡ，使体内潴留的尿素氮转而用于合成非必需氨基酸（ＮＥＡＡ），进而再被用于合成蛋白质，以减少蛋白质分解，降低氮质血症；②ＡＲＦ时，在有限的输液量中，２０％Ｉｎｔｒａｌｉｐｉｄ不失为一种低容量、高热卡的有效制剂，应予推崇。     

Evaluation of fat nutrition in the energy intake on low protein diets for patients with chronic renal failure]

Low protein diet has been proven to retard the progression of chronic renal failure. In this diet, the energy intake depends mainly on fats and carbohydrates instead of protein, and precautions should be taken against increasing risks of both lipid nephrotoxicity and atherosclerosis. In order to assess the adequacy of fat nutrition in a low protein diet for patients with chronic renal failure, we evaluated the total amounts of dietary fat intake, dietary individual fatty acid intake and serum individual fatty acid concentrations in 16 patients, whose mean creatinine clearance was 21.3 +/- 12.1 ml/m, serum creatinine 3.8 +/- 2.2 mg/dl and serum urea nitrogen 41.5 +/- 18.6 mg/dl. The percentage ratio of fat intake to total energy intake was 26.7 +/- 5.2%. The ratio of intake of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids was 1:2:1.8, and n-6/n-3 was 8.5 +/- 9.3. These were significant correlations between dietary intake and the serum concentrations in both EPA and the ratio of EPA/AA. Consequently, it might be considered that polyunsaturated fatty acids intake should be lowered and patients with chronic renal failure on a low protein diet should be advised about the proper selection of foods containing animal protein and plant-derived oil. It may be beneficial to recommend the intake of more EPA and lowering the ratio of n-6/n-3 intake might be useful in improving the fat nutrition to adequate levels in these patients.     

Effects of chronic intake of vegetable protein added to animal or fish protein on renal hemodynamics.

BACKGROUND/AIMS: To examine whether chronic intake of vegetable protein added to animal protein diet affects renal hemodynamics or not, we studied effects of three kinds of diets containing various amounts of animal and vegetable protein with 1-week dietary program in each on renal hemodynamics. METHODS: The crossover design of different amounts of vegetable protein added to the constant amount of animal protein was applied to two groups of 7 healthy individuals after the control dietary program. Renal function and 24 hours' urinary albumin excretion rate (AER) were examined on every 7th day of three consecutive 1-week dietary programs. RESULTS: Glomerular filtration rate (GFR; sodium thiosulphate clearance) and renal plasma flow (RPF) significantly decreased after decreasing the intake of animal protein by one third with keeping the amount of vegetable protein constant. The results when substituting vegetable protein for some of the animal protein in the diet without changing the total amount of protein were identical. The filtration fraction and AER did not change over the study periods regardless of dietary composition. CONCLUSION: The lack of an effect a 1-week intake of vegetable protein added to animal protein on GFR and RPF suggests that vegetable protein may be excluded from lists of restriction in low protein diet therapy in patients with renal insufficiency.     

Discovery and rediscovery of low protein diet

The basis of conservative treatment in chronic uremia is the restriction of protein, which lowers blood urea and diminishes nausea, vomiting and other uremic symptoms. Protein restriction to less than 25-30 g per day in adult patients may lead to negative nitrogen balance and protein depletion, which can be prevented by supplementing the diet with essential amino acids or a mixture of essential keto acid analogues and amino acids. The traditional view has been that low protein diet affords symptomatic relief in chronic uremia but does not effect the progression of renal failure. However, recent clinical results, mostly retrospective, suggest that protein restriction may retard or halt progression. This has led to a renewed interest in therapy with low protein diet and essential amino acids or keto analogues, since this form of treatment may postpone the time when the patient has to be started on dialysis, or even make dialysis unnecessary. It is not settled by which mechanism protein restriction effects progression of renal failure. According to one hypothesis, hyperphosphatemia (high Ca X P product) is harmful for the diseased kidneys; protein restriction is beneficial, since a low protein diet is generally also low in phosphate. An alternative hypothesis suggests that glomerular hyperfiltration in the remaining nephrons of the diseased kidneys is harmful and leads to glomerulosclerosis; low protein intake protects the kidney by abolishing glomerular hyperfiltration.