1 00:00:00,206 --> 00:00:02,080 JOHN ESSIGMANN: As I mentioned, I'm diabetic. 2 00:00:02,080 --> 00:00:07,770 And when things that I noticed in my dad, 3 00:00:07,770 --> 00:00:10,140 before he knew he was diabetic-- 4 00:00:10,140 --> 00:00:12,300 he'd come home from the train at night, 5 00:00:12,300 --> 00:00:17,830 and my sister and I would rub his legs, because they hurt. 6 00:00:17,830 --> 00:00:19,650 This is one of the problems with diabetics. 7 00:00:19,650 --> 00:00:21,360 His feet hurt. 8 00:00:21,360 --> 00:00:26,750 And I remember my sister Nancy saying once, gee. 9 00:00:26,750 --> 00:00:31,350 Daddy smells like Mommy's nail polish remover. 10 00:00:31,350 --> 00:00:33,280 Which was acetone. 11 00:00:33,280 --> 00:00:36,060 And acetone is one of the three ketone bodies, 12 00:00:36,060 --> 00:00:38,760 the other two being Beta-Hydroxybutyric 13 00:00:38,760 --> 00:00:41,340 acid and acetoacetate. 14 00:00:41,340 --> 00:00:44,370 So what happens in diabetes is, the diabetic 15 00:00:44,370 --> 00:00:48,090 doesn't have ample carbohydrate reserves within their cells 16 00:00:48,090 --> 00:00:53,430 as glycogen. So they're doing a lot of fatty acid oxidation, 17 00:00:53,430 --> 00:00:56,680 rather than carbohydrate metabolism. 18 00:00:56,680 --> 00:00:58,530 If you take a fatty acid, and you break it 19 00:00:58,530 --> 00:01:00,860 down to Acetyl-CoA, the last step 20 00:01:00,860 --> 00:01:03,250 is called Beta-ketothiolase-- backs up, 21 00:01:03,250 --> 00:01:05,670 then your two carbons of Acetyl-CoA 22 00:01:05,670 --> 00:01:08,920 will be four carbons of acetoacetate. 23 00:01:08,920 --> 00:01:12,840 And then acetoacetate-- a third Acetyl-CoA can add to it 24 00:01:12,840 --> 00:01:16,025 to form what's called hydroxy-methylglutaryl-coenzyme 25 00:01:16,025 --> 00:01:17,110 A-- 26 00:01:17,110 --> 00:01:18,900 HMG CoA. 27 00:01:18,900 --> 00:01:21,330 And then rearrangements can happen 28 00:01:21,330 --> 00:01:25,410 that give rise, ultimately, to the three ketone bodies-- 29 00:01:25,410 --> 00:01:27,420 acetoacetate, Beta-Hydroxybutyrate, 30 00:01:27,420 --> 00:01:29,470 and acetone. 31 00:01:29,470 --> 00:01:33,000 So in situations where-- of starvation-- 32 00:01:33,000 --> 00:01:36,770 and diabetes is basically, my cells 33 00:01:36,770 --> 00:01:39,150 were in a technical state of starvation. 34 00:01:39,150 --> 00:01:40,950 In a case of starvation, what happens 35 00:01:40,950 --> 00:01:45,570 is you get this backup of the lipid breakdown, 36 00:01:45,570 --> 00:01:46,890 or catabolism pathway. 37 00:01:46,890 --> 00:01:50,850 And then these ketone bodies flush out into your blood. 38 00:01:50,850 --> 00:01:53,580 In starvation situations, the ketone bodies 39 00:01:53,580 --> 00:02:00,550 will act as fuels for your brain and other organs. 40 00:02:00,550 --> 00:02:02,610 It's a difficult transition. 41 00:02:02,610 --> 00:02:04,640 But ketone bodies are-- 42 00:02:07,686 --> 00:02:09,060 in the case of diabetics, they're 43 00:02:09,060 --> 00:02:13,530 produced to excess, to such extent that they're actually 44 00:02:13,530 --> 00:02:14,940 quite harmful to you. 45 00:02:14,940 --> 00:02:18,120 The reason a person smells of acetone 46 00:02:18,120 --> 00:02:21,530 is the intermediate ketone body-- 47 00:02:21,530 --> 00:02:25,680 the acetoacetate basically decarboxylates. 48 00:02:25,680 --> 00:02:28,590 It's a Beta-keto acid, and so it's 49 00:02:28,590 --> 00:02:32,160 a spontaneous decomposition to form acetone. 50 00:02:32,160 --> 00:02:36,030 Acetone is not, to my knowledge, biochemically 51 00:02:36,030 --> 00:02:38,340 useful as a kind of an energy source. 52 00:02:38,340 --> 00:02:40,020 But it's a sentinel, or it's something 53 00:02:40,020 --> 00:02:47,720 that is smelled, so that it can be diagnostic of the disease.