Kidneys ketone bodies

In the liver, the ketone bodies suffer no transformation, and are excreted into the blood. The normal contents of ketone bodies (as acetoacetate or P-hydroxy-butyrate) amount to mere 0.1-0.6 mmol/ litre). Other tissues and organs (heart, lung, kidney, muscle, and nervous tissue), as distinct from the liver, utilize the ketone bodies as energy substrates. In the cells of these tissues, acetoacetate and 1-hydroxybutyrate enter ultimately the Krebs cycle and burn down to C02 and H,0 to release energy. 

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. 

Ketone bodies (acetoacetate, hydroxybutyrate) free liver cardiac muscle, brain, kidney, skeletal muscle, small intestine... 

Acetoacetate and 3-hydroxybutyrate are known as ketone bodies. They are classified as fat fuels since they arise from the partial oxidation of fatty acids in the liver, from where they are released into the circulation and can be used by most if not all aerobic tissues (e.g. muscle, brain, kidney, mammary gland, small intestine) (Figure 7.7, Table 7.1). There are two important points (i) ketone bodies are used as fuel by the brain and small intestine, neither of which can use fatty acids (ii) ketone bodies are soluble in plasma so that they do not require albumin for transport in the blood. 

Ketone bodies are oxidised by most aerobic tissues including skeletal muscle, heart, kidney, lung, intestine and brain. Since the last two cannot oxidise fatty acids, their ability to oxidise ketone bodies is very important, because they provide another fuel in addition to, or as an alternative to, glucose. Hence, they can be used to replace some of the glucose to maintain the blood glucose concentration (e.g. in prolonged starvation or hypoglycaemia). 

The kidney is an important organ that filters materials from the blood that are harmful, or in excess, or both. These materials are excreted in the urine. A number of tests are routinely run in clinical laboratories on urine samples. These involve the measurements of glucose or reducing sugars, ketone bodies, albumin, specific gravity, and pH. 

In the advanced stages of fasting, ketone bodies cease to provide substantial metabolic fuel for skeletal and heart muscle and kidneys. They are used almost exclusively by the brain, which also continues to use glucose, albeit in drastically lowered amounts. Muscle, heart, and kidneys depend exclusively on fatty acids for their subsistence. Glucose continues to be used exclusively by the... 

Ketone body utilization by heart, muscle, kidney 60 0... 

In starvation, the kidney uses glutamine, and glutamate derived from it, as a source of ammonia to buffer ketone bodies that are excreted. Some ammonia. goes to the liver for urea synthesis. The... 

Three ketone bodies are formed during the breakdown (metabolism) of fats acetoacetate, p-hydroxybutyrate, and acetone. They are produced to meet the energy requirements of other tissues. Fatty acids, produced by the hydrolysis of triglycerides, are converted to ketone bodies in the liver. They are removed by the kidneys... 

Because carbohydrate utilization is impaired, a lack of insulin leads to the uncontrolled breakdown of lipids and proteins. Large amounts of acetyl CoA are then produced by P-oxidation. However, much of the acetyl CoA cannot enter the citric acid cycle, because there is insufficient oxaloacetate for the condensation step. Recall that mammals can synthesize oxaloacetate from pyruvate, a product of glycolysis, but not from acetyl CoA instead, they generate ketone bodies. A striking feature of diabetes is the shift in fuel usage from carbohydrates to fats glucose, more abundant than ever, is spurned. In high concentrations, ketone bodies overwhelm the kidney s capacity to maintain acid-base balance. The untreated diabetic can go into a coma because of a lowered blood pH level and dehydration. 

Tissues that can use ketones as "fuel" brain, muscle, kidney, intestine P-hydroxybutyrate + NAD+ —> NADH + acetoacetate acetoacetate + succinyl CoA —> acetoacetyl CoA + succinate acetoacetyl CoA + CoA —> 2 acetyl CoA Ketone Bodies as Fuel... 

A deficiency purely in pantothenic acid has probably never occurred, except in controlled studies. Persons suffering from severe malnutrition would be expected to be deficient in the vitamin. Studies with animals have shown that consumption of a diet deficient in the vitamin results in a loss of appetite, slow growth, skin lesions, ulceration of the intestines, weakness, and eventually death. Pantothenic acid deficiency also results in the production of gray fur in animals whose fur is colored. Biochemical studies with deficient animals have revealed severe decreases in pantothenic acid levels in a variety of tissues, but only moderate declines in the levels of coenzyme A in liver and kidney and maintenance of coenz)nne A levels in the brain (Smith et ah, 1987). Some striking defects in glycogen and ketone body metabolism have been noted in pantothenic acid-deficient animals. 

Hypoventilation causes retention of C02 by the lungs, which can lead to a respiratory acidosis. Hyperventilation can cause a respiratory alkalosis. Metabolic acidosis can result from accumulation of metabolic acids (lactic acid or the ketone bodies p-hydroxybutyric acid and acetoacetic acid), or ingestion of acids or compounds that are metabolized to acids (methanol, ethylene glycol). Metabolic alkalosis is due to increased HC03, which is accompanied by an increased pH. Acid-base disturbances lead to compensatory responses that attempt to restore normal pH. For example, a metabolic acidosis causes hyperventilation and the release of C02, which tends to lower the pH. During metabolic acidosis, the kidneys excrete NH4+, which contains H+ buffered by ammonia. 

Ketone bodies are used as fuels by tissues such as muscle and kidney. During starvation (after about 3-5 days of fasting), the brain also oxidizes ketone bodies. 

When ketone bodies are released from the liver into the blood, they are taken up by peripheral tissues such as muscle and kidney, where they are oxidized for energy. 

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