10/12 Energy from Ketones

Question 1

what is ethanol metabolized to (1st, then 2nd)

Answer 1

acetaldehyde (toxic)
acetic acid (vinegar)

Question 2

what enzyme metabolizes ethanol to acetaldehyde

Answer 2

alcohol dehydrogenase 1B

Question 3

what enzyme metabolizes acetaldehyde to acetic acid

Answer 3

aldehyde dehydrogenase 2

Question 4

where/how/why are ketones made

Answer 4

fasted state, when ATP needs are met, amount of acetylCoA continues to rise because no feedback inhibition of FA oxidation, but high NADH levels have shut off Krebs cycle. acetyl CoA shunted into ketone production in the liver

Question 5

two main types of ketones (and third, kinda)

Answer 5

B-hydroxybutyrate (BHB)
Acetoacetate
[Acetone (can be formed by nonenzymatic rxn from acetoacetate, metabolically inert)]

Question 6

what tissues can [not] use FAs for energy

Answer 6

Yes: muscle, liver, heart
No: RBCs, brain

Question 7

what tissues can use ketones for energy

Answer 7

muscle, heart, brain

Question 8

what hormone drives ketone production

Answer 8

glucagon (cAMP)

Question 9

what enzyme makes ketones, and regulation

Answer 9

HMG-CoA synthase

(+) cAMP
(+) free fatty acids

Question 10

ketones after 12 hours fasted

Answer 10

ketones are supplemental E to fatty acids

Question 11

ketones after 3 days fasted

Answer 11

ketons become major E source for the brain

glycogen is gone –> gluconeogenesis is solely responsible for maintaining blood glucose levels

Question 12

protein degredation after 3 days fasted

Answer 12

drop in brain glucose use means less muscle wasting (drop in protein degredation to use AA as E) and less E consumed to make/remove urea

Question 13

how can a T1D be hyperketotic and hyperglycemic

Answer 13

lack of insulin signal keeps glucose in the blood, and nothing to stop production of ketones after FA oxidaiton

results in ketoacedosis and dehydration (poss. coma)

glucagon dominates

Question 14

in times of low blood insulin, what protein is absent from cell surfaces

Answer 14

GLUT4 (fat and mm need to take up glucose)

Question 15

how does MCAD deficiency lead to hypoketosis and hypoglycemia

Answer 15

no B-oxidation of medium chain FAs = lack of NADH, FADH2, and AcCoA

in fasted state, glycogen stores are too small to maintain blood glucose and results in hypoglycemia, cannot produce ketones b/c no AcCoA and results in hypoketosis

Question 16

what is succinyl-CoA made from

Answer 16

odd chain fatty acids

VoMIT

Question 17

enzyme used to oxidize ketone bodies

Answer 17

acetoacetate CoA transferase

Question 18

why do alcoholics have chronically high NADH levels

Answer 18

side product of acetaldehyde metabolism to acetone is NADH

enzyme is aldehyde dehydrogenase

Question 19

effects of acetaldehyde accumulation

Answer 19

protein/dna damage –> cancer

flushing, throbbing headache, respiratory difficulty, thirst, nausea, vomiting, sweating

Question 20

drug for alcoholism

Answer 20

Antabuse (disulfiram)
inhibits aldehyde dehydrogenase 2, causing accumulation of aldehyde and unsavory symptoms after drinking alcohol
used with naltrexone and acamprosate

Question 21

what causes gout

Answer 21

metabolism of acetate (acetic acid) in heart and skeletal muscle causes an increase in AMP, causing degredation of the AMP/GMP pathways, increasing uric acid

urate crystals precipatate in joints, causing painful inflammation

Question 22

effect of high NADH on pyruvate

Answer 22

metabolism of ethanol increases NADH
high NADH shunts pyruvate to lactate
inhibits FA oxidation
increases TG synthesis
inhibits vLDL release
inhibits liver gluconeogenesis
results in fatty liver, liver damage, cirrhosis, hypoglycemia