Ketone Bodies

Question 1

ketone bodies definition

Answer 1

water soluble molecules that are produced by the liver during long periods of fasting and starvation and can act as alternative fuels to power our bodies

Question 2

2 main ketones

Answer 2

acetoacetate and beta hydroxybutyrate

Question 3

what is the third one?

Answer 3

acetone, volatile and smells like pear drops

Question 4

ketogenesis definition

Answer 4

the production of ketone bodies within liver mitochondria

Question 5

ketolysis definition

Answer 5

the breakdown and utilisation of ketone bodies that occurs in peripheral tissues and most importantly the brain and nerve cells

Question 6

where does the process begin?

Answer 6

adipose tissue

Question 7

explain how + why ketogenesis begins

Answer 7

hormone sensitive lipase is active in fasting, as in the fasting state insulin levels are low, so there is none to inhibit the process

therefore triacylglycerols are broken down and released to produce NEFAs that travel in the blood bound to albumiin

Question 8

how does insulin normally act?

Answer 8

inhibits protein phosphatase, so less HSL is dephosphorylated, so more is active

Question 9

what occurs before ketogenesis?

Answer 9

fatty acids are broken down to produce acetyl CoA molecules in beta oxidation

Question 10

stages of ketogenesis

Answer 10

1. acetyl CoA + acetyl CoA forms acetoacetyl CoA catalysed by acetoacetyl CoA thiolase
2. another acetyl CoA molecule is added to acetoacetyl CoA to produce HMG- CoA catalysed by HMG-CoA synthase
3. HMG CoA lyase then catalyses the conversion to acetoacetate with the release of an acetyl CoA molecule
4. spontaneous decarboxylation then produces acetone
5. enzymic oxidation of acetoacetate produces ebeta hydroxybutyrate- catalysed by beta hydroxybutyrate dehydrogenase and NADH + H+
6. The ketone bodies are then released into the blood

Question 11

which ketone body has the highest concentration in the blood?

Answer 11

b-hydroxybutyrate, as this is formed from acetoacetate

Question 12

what makes acetyl CoA become diverted from TCA?

Answer 12

oxaloacetate is diverted to gluconeogenesis, so there is less available to combine with acetyl CoA so all can’t enter the TCA cycle, instead diverted into ketogenesis

Question 13

what is the rate of uptake of ketone bodies by the peripheral tissues proportional to?

Answer 13

the concentration in blood and thus the rate of production

Question 14

where does ketolysis not take place + why?

Answer 14

the liver

does not have 2-ketoacyl CoA transferase required for the process

Question 15

ketolysis stages

Answer 15

1. beta hydroxybutyrate with NAD to NADH and acetoacetate catalysed by beta hydroxybutyrate dehyrdogenase
2. acetoacetate to acetoacetyl CoA using succinylcholine CoA ro succinate and catalysed by 3-ketoacyl CoA transferase
3. acetoacetyl CoA and CoASHto two acetyl COA molecules, catalysed by acetoacetyl CoA thiolase, and thus can enter Krebs

Question 16

why make ketones?

Answer 16

brains cannot use fatty acids, only glucose. ketone bodies provide an alternate fuel

ketones are glucose sparing so without them there would be insufficient glucose to keep the body going

Question 17

which disease is greatly impacted by ketogenesis?

Answer 17

type 1 diabetes melitutus

Question 18

explain effect on diabetes melitus

Answer 18

uncontrolled ketosis, no insulin to regulate hormone sensitive lipase

kept acids drop pH of blood, leading to ketoacidosis

cause rapid breathing Kussmaul breathing and smell acetone on breath

Question 19

different concentrations of ketone bodies

Answer 19

normal blood 0.1mmol/l

fasting ketosis 4-6mmol/l

diabetic ketoacidosis can reach 20-30mmol/l but action needed if exceed 5mmol/l