Topic 7: Energy Production: Ketone Bodies

Question 1

what is the main convergence point for catabolic pathways

Answer 1

acetyl coA - activated

Question 2

what are the functions of acetyl coA

Answer 2

intermediate in both catabolic and anabolic pathways
used to form fatty acid -> triacylglycerols and phospholipids
used to form CO2
used to form hydroxymethylglutaric acid -> ketone bodies and cholesterol -> steroid hormones

Question 3

what are the three ketone bodies produced in the body

Answer 3

acetoacetate (CH3COCH2COO-) - liver
acetone (CH3COCH3)
beta-hydroxybutyrate (CH3CHOHCH2COO-) liver

Question 4

what is the normal plasma ketone body concentration

Answer 4

less than 1mM

Question 5

what is the concentration of ketone bodies in starvation

Answer 5

2-10mM

Question 6

untreated diabetes causes how much ketone bodies to form

Answer 6

more than 10mm (PATHOLOGICAL KETOSIS)

Question 7

what are ketone bodies synthesised by

Answer 7

liver mitochondria

Question 8

how are ketones bodies formed

Answer 8

acetyl coA + synthase forms hydroxymethyl glutaryl coA
this can form mevalonate ( HMG-coA reductase) for cholesterol
or to acetoacetata (lyase) which can then form acetone or beta-hydroxybutyrate

Question 9

what is used in statin drugs as well as in ketone body formation

Answer 9

HMG-CoA reductase

Question 10

how is the production of ketone bodies controlled

Answer 10

low glucose - glycolysis reduced, mobilises fatty acids from adipose stores which form acetyl coA and NADH
NADH produces product inhibition in krebs cycle so less NAD+, so build up of citrate
acetyl coA can not enter krebs cycle so diverted to ketone body production

Question 11

what happens to acetoacetate

Answer 11

transported as acetone and betahydroxybutyrate in blood
beta hydroxybutryate oxidised to acetoacetate -> picks up coA from krebs cycle -> converted to acteyl coA -> feeds in krebs cycle

Question 12

how is ketone body synthesis regulated

Answer 12

insulin/glucagon ration - fed state
when insulin/glucagon ration high (fed state - lots of insulin) - lyase is inhibited, reductase activated, towards cholesterol synthesis
when insulin/glucagon ration low (starvation state - lots of glucagon) - lyase activated and reductase inhibited, towards ketone body synthesis

Question 13

what is the function of ketone bodies

Answer 13

spare glucose in early starvation/diabetes:
fatty acid - ketogenesis - ketone bodies - into muscle - acetyl coA - krebs cycle - CO2 and energy
brain requires remaining glucose
in late starvation - breakdown of muscle protein to amino acids to liver, converted via gluconeogensiss to glucose to supply brain

Question 14

what are some features of ketone bodies

Answer 14

water soluble
permit high plasma concentration - permit transport of energy fuel between tissues
alternative subtrate

Question 15

if ketone body conc rise above renal theshold

Answer 15

excreted in urine -> ketonuria

Question 16

what can acetoacetate and beta-hydroxybutyrate cause

Answer 16

ketoacidosis (strong acids)

Question 17

how is acetone excreted

Answer 17

if volatile - via lungs
characteristic smell (early starvation)

Question 18

what would happen if genetic defect that prevented synthesis of one of the enzymes of the TCA cycle

Answer 18

tissues such as the CNS and heart not obtain energy to function