Ketone bodies circulation

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 (KBs) circulate in the blood as (CH3-CHOH-CH2-COOH) and ACAC (CH3-CO-CH2-COOH). The blood concentrations of these two metabolites depend upon the equilibrium between their production by the liver (ketogen-esis) and consumption at the peripheral level (ketogenolysis). Abnormalities of KB metabolism manifest as ketosis, hypoketotic hypoglycaemia and inversion of the 30HB arachidonic acid (AA) ratio [12]. 

The liver converts fatty acids to triacyiglycerols, phospholipids, or cholesterol and its esters, for transport as plasma lipoproteins to adipose tissue for storage. Fatty acids can also be oxidized to yield ATP or to form ketone bodies, which are circulated to other tissues. 

Ition of the ketone bodies may be as high as 5000 mg/24 hr, and the blood concentration may reach 90 mg/dl (versus less than 3 mg/dL in normal individuals). A frequent symptom of diabetic ketoacidosis is a fruity odor on the breath which result from increased production of acetone. An elevation of the ketone body concentration in the blood results in acidemia. [Note The carboxyl group of a ketone body has a pKa about 4. Therefore, each ketone body loses a proton (H+) as it circulates in the blood, which lowers the pH of the body. Also, excretion of glucose and ketone bodies in the urine results in dehydration of the body. Therefore, the increased number of H+, circulating in a decreased volume of plasma, can cause severe acidosis (ketoacidosis)]. Ketoacidosis may also be seen in cases of fasting (see p. 327). 

During the first 2 weeks of fasting, muscle uses fatty acids from ad-pose tissue and ketone bodies from the liver as fuels (Figure 24.14, O and ). After about three weeks of fasting, muscle decreases its use of ketone bodies and oxidizes fatty acids almost exclusively. This leads to a further increase in the already elevated level of circulating ketone bodies. [Note The increased use of ketone bodies by the brain as a result of their increased concentration in the blood is correlated with the decreased use of these compounds by the muscle.]... 

Although acetone is a very minor product of normal metabolism, diabetics whose disease is not well-managed often have high levels of ketone bodies in their circulation. The acetone that is formed from decarboxylation of acetoacetate is excreted through the lungs, causing characteristic acetone breath. ... 

The brain relies on the circulation for nutrients and is a chief consumer of glucose. The brain uses about 15 percent of the energy required for minimal maintenance of body functions (called the basal metabolic rate). Brain tissue doesn t store energy. Instead, the brain must rely on the circulation for its fuel supply. Not all molecules can be transported across the blood-brain barrier to be used for energy. One molecule that can cross the blood-brain barrier is glucose, the preferred fuel source for the brain. Brain tissue can also adapt to ketone bodies such as acetoacetate as a source of fuel. 

FIGURE 4,65 Synthesis, circulation, and de adatiun of ketone bodies. Ketone body metabolism involves synthesis in the mitochondria of the fiver, distribution via the bloodstream, and oxidation by the Krebs cycle in various organs, such as ihe brain and muscle,... 

Acetoacetate and p-hydroxybut)rrate are produced primarily in the liver. These metabolites diffuse into the blood and are circulated to other tissues, where they may be reconverted to acetyl CoA and used to produce ATP. In fact, the heart muscle derives most of its metabolic energy from the oxidation of ketone bodies, not from the oxidation of glucose. Other tissues that are best adapted to the use of glucose will increasingly rely on ketone bodies for energy when glucose becomes imavailable or limited. This is particularly true of the brain. 

The fatty acids are converted to short-chain oxy acids usually called ketone bodies, such as P-hydroxybutyrate and P-ketobutyrate, which are highly water soluble and are circulated easily in the blood. The ketone bodies are efficient nutrients because they enter directly into the mitochondria for aerobic metabolism. The heart uses ketone bodies all the time. Adipose tissue surrounds the heart and even permeates into it, providing a direct and efficient energy supply for this constantly working tissue. The brain adapts to the use of ketone bodies as nutrients... 

---