Origin of the Body Uric Acid Pool in Humans

The body pool of urate, and hence the plasma urate concentration, is the result of a balance between production, ingestion, and excretion. The main causes of high plasma uric acid concentrations are high intake of exogenous nucleic acid in the diet and overproduction of endogenous purine. Eating less meat, seafood, and other high-purine foods (Tables 1 and 2) leads to a lower dietary intake of nucleic acids. In contrast, subjects with genetic defects that remove the usual controls on purine biosynthesis may have overwhelmingly high endogenous levels of the waste product, uric acid.

The contribution of the two sources can be assessed by placing the subject on a purine-free diet for 1 week and measuring the urinary uric acid. In this way, fewer than 5% of patients with gout have been found to excrete abnormally large amounts of urate (>3mmol/day) derived from endogenous

Filtration

82-92% Reabsorption

Excretion

Figure 4 Schematic diagram showing the role of the kidney in influencing plasma uric acid concentration. In the brush border membrane of the proximal tubule, reabsorption by the urate anion exchanger and secretion via a voltage-sensitive pathway both occur. This results in a mean fractional urinary excretion of only 8-18% of the filtered load in healthy subjects and 5% or less in 'primary' gout. The net uric acid reabsorption is (A) higher in healthy men (92%) than in women (88%) and lower in children of either sex (82%), and (B) much higher in middle-aged males with primary gout (95%).

Table 1 Reference guide to the purine content of foods

Foods and beverages rich in nucleic acids/purines

Offal: sweetbreads, liver, kidney, heart, and pate Wild or farmed game meats (venison, pheasant, rabbit, hare) Seafoods: sardines, sprats, herring, bloaters, anchovies, fish roe, caviar, taramasalata, trout or salmon, lobster, crab, prawns

Vegetables: asparagus, avocado pears, peas, spinach, mushrooms, broad beans, cauliflower Pulses and grains: legumes, pulses and soya products such as bean curd, tofu, Quorn Cereals: all bran, oat, rye, or wheat cereals and products; whole meal, rye, and brown breads Other: beer and yeast extracts/tablets (Barmene, Tastex); meat or vegetable extracts (Marmite, Vegemite, Bovril, Oxo)

Foods that are moderate or low sources of purine

Beef, lamb, pork (steak or chops), bacon, ham, sausages, some poultry, tongue (all should be eaten in moderation) Carrots, parsnip, potatoes, lettuce, leeks, cabbage, sprouts, marrow, courgettes Peanuts, cashew nuts

White bread or flour, cakes, scones, biscuits, cereals

Some fish (see Table 2)

Foods and beverages that are purine-free

Milk, cheese, eggs, butter, margarine, cream, ice cream

Sugar, jam, marmalade, honey, sweets

Cucumber, tomato, onions, pumpkin

Fresh, cooked or tinned fruits, nuts

Puddings, custards, yogurt

Fruit juices, soft drinks

Table 2 Concentrations of purines in some common foods and beverages3

Food Purine (mg/100g) Protein (mg/100g) Meat

Beef liver 333

Beef kidney 285

Beef heart 285

Beef tongue 167

Beefsteak 151

Calf liver 348

Sweetbreads 1212

Veal cutlet 152

Sheep kidney 312

Lamb chop 196

Pork liver 289

Pork cutlet 164

Bacon 85

Ham 136

Sausage (beef) 79

Sausage (pork) 66

Rabbit 118

Venison 156

Vegetables

Asparagus 32

Cauliflower 32

Celery 20

Kohlrabi 44

Mushrooms 72

Peas 72

Spinach 96

Dried legumes

Split peas 195 21

Red bean 162 20

Lentils 222 28

Haricot beans 230 22

Lima bean 149 21

Other

Bovril 340 18

Marmite 356 2

Oxo cubes 236 10

Yeast extracts 2257 46

Poultry

Chicken flesh 181 20.6

Chicken liver 372 22.1

Chicken heart 223 18

Duck 181 16

Goose 177 16.4

Turkey 239 20.1

Fish, seafoods

Anchovies 411 20

Bass 73 19.5

Bloaters 133 22.6

Bream 72 19.7

Cod 62 18

Crab 61 19.2

Clams 136 17

Eel 108 18.6

Fish cakes 36 12.1

Herring 378 17

Kippers 91 21.2

Lobster 100 20

Lemon sole 54 19.9

Mackerel 246 29

Plaice 53 18.1

Salmon 250 23

Sardines 345 23

Scallops 117 22.3

Sprats 250 25.1

Squid 135 15

Trout 92 19.2

Canned seafoods

Anchovies 321 30

Herring 378 17

Mackerel 246 26

Oysters 116 6

Salmon 88 26

Sardines 399 24

Shrimp 231 22

Tuna 142 29

aResults are recorded relative to 100 g of food for purine and for protein, although serving size for each ingredient may be larger or smaller than 100 g.

purines. In these cases, overproduction of purine nucleotides leading to excess uric acid can be traced to a genetic defect. Two such sex-linked disorders are hypoxanthine-guanine phosphoribosyltransfer-ase (HPRT) deficiency and phosphoribosyltransfer-ase superactivity (PRPS). Boys presenting in infancy usually have severe and eventually fatal neurological deficits. Neurological problems are milder or absent,

16.8

16.4

19.5

16.4

and only gout may be evident, in those presenting as adolescents. It is important for clinicians to be aware of these disorders, especially when encountering a young patient with gout or an older male with a history dating back to adolescence. In some families, siblings are also affected, and although the gout symptoms can be alleviated, other aspects are less amenable to treatment and genetic counselling should be given.

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