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The NuGOwiki Metabolite Database is a joint initiative of NuGO and HMDB
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| Beta-hydroxybutyrate | |
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| Chemical Name | (3R)-3-hydroxybutanoic acid |
| Chemical Formula | C4H8O3 |
| CAS Number | 625-72-9 |
| Chemical Information | HMDB00011 |
| Biochemical Taxonomy | Not Available |
| Functional Taxonomy | Not Available |
| Nutritional Taxonomy | Not Available |
| Metabolic Pathways |
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| Biofluid Location |
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| Tissue Location |
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| Normal Biofluid Concentrations |
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| Normal Tissue Concentrations | Not Available |
| Diseases / Conditions Related to Nutrition |
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| Other (Monogenic Disorders) |
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| Abnormal Biofluid Concentrations |
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| Abnormal Tissue Concentrations | Not Available |
| Physiological Processes | Not Available |
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Contents |
Introduction
guidelines
An organic acid involved in the synthesis and degradation of ketone bodies. Also known as one of the ketone bodies produced in the liver and occurring at high levels in the blood and urine in ketosis. This acid is metabolized by 3-hydroxybutyrate dehydrogenase (catalyzes the oxidation of D-3-hydroxybutyrate to form acetoacetate, using NAD+ as an electron acceptor). The enzyme functions in nervous tissues and muscles, enabling the use of circulating hydroxybutyrate as a fuel. In the liver mitochondrial matrix, the enzyme can also catalyze the reverse reaction, a step in ketogenesis.
Beta-hydroxybutyrate is an organic acid and also known as one of the ketone bodies; the others being acetoacetate and acetone. Ketone bodies are produced exclusively in the mitochondrial matrix of the liver, and their biosynthesis is closely related to fatty acid metabolism. Biosynthesis of beta-hydroxybutyrate starts from 2 acetyl-CoA that are connected by ketothiolase to acetoacetyl-CoA. Another acetyl-CoA is added by HMG-CoA synthetase to form beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA). HMG-CoA lyase now cleaves off acetyl-CoA to yield acetoacetate, which can be reduced to beta-hydroxybutyrate by beta-hydroxybutyrate dehydrogenase using NADH as hydrogen donor. Beta-hydroxybutyrate is the major ketone body. Since, it is water-soluble it can diffuse into the bloodstream and be transported to other organs.
Biological Function
guidelines
Beta-hydroxybutyrate (and acetoacetate) can be used as energy supply for extrahepatic tissues, especially kidney and muscle in the physiological state, after prolonged fasting (several days) the CNS can also adapt to utilize ketone bodies as energy substrates. They can be viewed as water soluble stores for acetyl-CoA.
Catabolism
guidelines
Although the liver produces ketone bodies, it can not use them as energy substrates. After its biosynthesis beta-hydroxybutyrate is transported to extrahepatic tissues where it can be used for lipid synthesis (brain) or as energy substrate (muscle, kidney, brain after adaptation). In the mitocholdrial matrix beta-hydroxybutyrate can be oxidised back to acetoacetate by beta-hydroxybutyrate dehydrogenase using NAD+ as hydrogen acceptor. Acetoacetate in turn can accept a CoA moiety from succinyl-CoA to yield acetoacetyl-CoA and succinate - a reaction catalysed by ketoacyl-Coa-transferase. Acetoacetyl-CoA can now enter beta-oxidation where it is cleaved to two molecules of acetyl-CoA, which can enter several pathways(e.g. TCA cycle).
Diseases / Conditions Related to Nutrition
- Bacterial meningitis
- Diabetes
- Diabetic Ketoacidosis
There are several conditions in which levels of beta-hydroxybutyrate are increased in the blood (ketosis), e.g. diabetes mellitus, fasting (especially children), alcoholism. Since beta-hydroxybutyrate (and acetoacetate) are acids (pKa=4.39 and 3.58, respectively), a strong accumulation of ketone bodies can lead to a drop in blood pH, resulting in ketoacidosis. This can happen especially in diabetes mellitus type I, when it has not been diagnosed yet, or when insulin doses have been omitted. In that case glucose cannot be taken up into cells, fatty acids are broken down and large amounts of ketone bodies are produced.
In hypoglycaemia, low levels indicate one of the non-ketotic causes of hypoglycaemia (eg, hyperinsulinism).
Other (Monogenic) Disorders
- 3-@hydroxy-3-methylglutaryl-coa synthase 2, mitochondrial, deficiency OMIM: 605911
Nutritional Information
Drivers for biological variation
Stimulation of glucose metabolism is known to inhibit ketogenesis by action of insulin. This leads to decreased concentrations of beta-hydroxybutyrate at 60, 90 and 120 minutes after a glucose challenge (Shaham et al Pubmed).
Vulnerable groups
Other resources
- Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals, American Journal of Clinical Nutrition