Ketones. Biochemistry
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- Angelina Carter
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1 Ketnes Bichemistry Acetne, acetacetate and beta-hydrxybutyrate are ketnes (r ketne bdies) generated frm carbhydrates, fatty acids and amin acids in humans and mst vertebrates. Ketnes are elevated in bld after fasting including a night f sleep, and in bth bld and urine in starvatin, hypglycemia due t causes ther than hyperinsulinism, varius inbrn errrs f metablism, and ketacidsis (usually due t diabetes mellitus). Althugh ketacidsis is characteristic f decmpensated r untreated type 1 diabetes, ketsis r even ketacidsis can ccur in type 2 diabetes in sme circumstances as well. Acetacetate and beta-hydrxybutyrate are an imprtant fuel fr many tissues, especially during fasting and starvatin. The brain, in particular, relies heavily n ketne bdies as a substrate fr lipid synthesis and fr energy during times f reduced fd intake. At the NIH, Dr. Richard Veech refers t ketnes as "magic" in their ability t increase metablic efficiency, while decreasing prductin f free radicals, the damaging byprducts f nrmal metablism. His wrk has shwn that ketne bdies may treat neurlgical diseases such as Alzheimer's and Parkinsn's disease, [4] and the heart and brain perate 25% mre efficiently using ketnes as a surce f energy. [5] Applicatins Ketnes are ften used in perfumes and paints t stabilize the ther ingredients s that they dn't degrade as quickly ver time. Other uses are as slvents and intermediates in chemical industry. Examples f ketnes are acetne, acetphenne, and methyl ethyl ketne. Uses in the heart and brain Ketne bdies can als be used fr energy. Ketne bdies are transprted frm the liver t ther tissues, where acetacetate and beta-hydrxybutyrate can be recnverted t acetyl-ca t prduce energy, via the Krebs cycle. 1
2 The heart gets much f its energy frm ketne bdies, althugh it als uses fatty acids. The brain gets its energy frm ketne bdies when insufficient glucse is available (e.g., when fasting). In the event f lw bld glucse, mst ther tissues have additinal energy surces besides ketne bdies (such as fatty acids), but the brain des nt. After the diet has been changed t lwer bld glucse fr 3 days, the brain gets 30% f its energy frm ketne bdies. After 4 days, this ges up t 70% (during the initial stages the brain des nt burn ketnes, since they are an imprtant substrate fr lipid synthesis in the brain). The brain retains sme need fr glucse, because ketne bdies can be brken dwn fr energy nly in the mitchndria, and brain cells' [citatin needed] lng thin axns are t far frm mitchndria. Prductin Acetyl-CA Ketne bdies are prduced frm acetyl-ca (see ketgenesis) mainly in the mitchndrial matrix f liver cells when carbhydrates are s scarce that energy must be btained frm breaking dwn fatty acids. Acetne is frmed frm spntaneus decarbxylatin f acetacetate. In a crrespnding manner, the levels f acetne are much lwer than thse f the ther tw types f ketne bdies. And, unlike the ther tw, acetne cannt be cnverted back t acetyl- CA, s it is excreted in the urine and exhaled (it can be exhaled readily because it has a high vapr pressure and thus evaprates easily). The exhalatin f acetne is respnsible fr the characteristic "fruity" dur f the breath f persns in kettic states. 2
3 Ketsis and ketacidsis Any prductin f these cmpunds is called ketgenesis, and this is necessary in small amunts. But, when excess ketne bdies accumulate, this abnrmal (but nt necessarily harmful) state is called ketsis. Ketsis can be quantified by sampling the patient's exhaled air, and testing fr acetne by gas chrmatgraphy. When even larger amunts f ketne bdies accumulate such that the bdy's ph is lwered t dangerusly acidic levels, this state is called ketacidsis. Impact upn ph Bth acetacetate and beta-hydrxybutyrate are acidic, and, if levels f these ketne bdies are t high, the ph f the bld drps, resulting in ketacidsis. This happens in untreated Type I diabetes (see diabetic ketacidsis), and als in alchlics after binge drinking, subsequent starvatin, and the alchl-induced impairment f the liver's ability t generate glucse (glucnegenesis)(see alchlic ketacidsis). Ketnes tests A ketne test checks fr ketnes in yur bld r urine. Ketnes are substances that are made when the bdy breaks dwn fat fr energy. Nrmally, yur bdy gets the energy it needs frm carbhydrate in yur diet. Hwever, stred fat is brken dwn and ketnes are made if yur diet des nt cntain enugh carbhydrate t supply the bdy with sugar (glucse) fr energy r if yur bdy cannt use bld sugar (glucse) prperly. Newer hme bld sugar meters can als measure ketnes. Hme urine tests t measure ketnes are available. 3
4 Why It Is Dne A bld test is the mst accurate methd f measuring ketnes. It is recmmended fr all peple with diabetes whenever symptms f illness are present, such as nausea, vmiting, r abdminal pain. These symptms are similar t symptms f high bld sugar and may mean yu have diabetic ketacidsis, a ptentially lifethreatening cnditin. A urine test is the mst cmmnly used methd f measuring ketnes. But it is less accurate than a bld test. It may be dne t: Mnitr a persn n a very lw-carbhydrate diet. Mnitr a pregnant wman wh has diabetes r has develped gestatinal diabetes. Results A ketne test checks fr substances made when the bdy breaks dwn fat fr energy (ketnes). Ketnes Nrmal: Urine test There are n ketnes in yur bld r urine. Abnrmal: Ketnes are present in yur bld r urine. If either the test strip r the urine changes clr when the tablet is drpped int the sample, ketnes are present in yur urine sample. The test results are read as negative t 1+ t 4+ r small t large. High values 4
5 Yu may have ketnes in yur urine if yu: Have prly cntrlled diabetes r diabetic ketacidsis. Are n a very lw-carbhydrate diet. Are starving r have an eating disrder, including disrders that result in pr nutritin such as anrexia nervsa r bulimia, alchlism, r pisning frm drinking rubbing alchl (isprpanl). Have nt eaten (fasted) fr 18 hurs r lnger. Are pregnant. Hwever, a mderate amunt f ketnes in a pregnant wman may harm the fetus and may be an indicatin f gestatinal diabetes. The level f ketnes, and nt just the presence f ketnes, may be imprtant t yur dctr as well. Many cnditins can change ketne levels. Fasting usually causes nly mild increases in the level, but ketne levels in diabetic ketacidsis are much higher. Yur health prfessinal will discuss any significant abnrmal results with yu in relatin t yur symptms and medical histry. What Affects the Test Reasns yu may nt be able t have the test r why the results may nt be helpful include: Taking medicines, such as: Levdpa, such as Sinemet r Lardpa. Phenazpyridine, such as Pyridium, Geridium, Pyridiate, r Urgesic. Valpric acid, such as Depakte, Depacn, r Depakene. Vitamin C (ascrbic acid), when taken in large amunts. Dehydratin. A high-fat diet. Pregnancy. What T Think Abut 5
6 The bld test can check fr ne type f ketne that the urine test cannt detect. Therefre, a urine test that des nt shw any ketnes may nt be accurate (false-negative result). Ketne levels will increase in yur urine befre they increase in yur bld if yu are fasting r n a very lw carbhydrate diet. The American Diabetes Assciatin recmmends that yu test yur urine fr ketnes if yu have diabetes and yu: Are pregnant. Are sick r feeling very stressed. Have bld sugar levels f 300 mg/dl (16.7 mml/l) r higher. Have symptms f high bld sugar (diabetic ketacidsis), such as nausea, vmiting, r abdminal pain. Ketnes can be tested at hme using urine ketne test strips. A mre accurate reading can be btained by sme hme glucse meters that test fr bld ketnes. 6
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