Ketogenesis

Question 1

what cells produce ketone bodies?

Answer 1

liver cells

Question 2

when does hepatic ketogenesis increase?

what events promote this activity?

Answer 2

in the fasting state

• low level of insulin and high level of glucagon in the blood > increase in supply of fatty acids from adipose > an increase in beta oxidation of fatty acids in liver cells >
  an increase in NADH and acetyl CoA in mitochondria of liver cells
• high NADH (high NADH/NAD+ ratio) > OAA becoming unavailable for reaction with acetyl Co
• high acetyl CoA and unavailability of OAA > increased use of acetyl CoA to make ketone bodies

Question 3

possible fates for the acetyl CoA being made by beta-oxidation

Answer 3

1. acetyl CoA reacts with OAA to make citrate

2. ketogenesis (making ketone bodies)

Question 4

name the enzyme:

acetyl CoA + OAA ————–> citrate

Answer 4

citrate synthase

Question 5

what location does the citrate synthase rxn happen in?

Answer 5

mitochondrial matrix (1st rxn of the TCA cycle)

Question 6

what slows down the TCA cycle?

Answer 6

NADH being created in the beta-oxidation cycle. NADH assists OAA in disguising itself as malate to get out of the mito matrix into the cytosol for the continuation of ketogenesis.

So it’s less likely to find OAA at this time to enter the TCA cycle and more likely to take the ketogenesis route

Question 7

name the process:

acetyl CoA —> acetoacetyl CoA —> ketone bodies

Answer 7

ketogenesis

Question 8

___________________ is induced in the fasting state which makes ketogenesis more possible

Answer 8

mitochondrial HMG-CoA synthase

Question 9

intracellular compartment for ketogenesis

Answer 9

mitochondrial matrix

Question 10

starting material for ketogenesis

Answer 10

mitochondrial acetyl CoA

Question 11

summarize about the formation of hydroxymethylglutaryl CoA (HMG CoA) catalyzed by the mitochondrial version of HMG CoA synthase

Answer 11

3 acetyl groups (from 3 mitochondrial acetyl CoA) are used to produce 1 HMG group that has 6 carbons (hydroxymethylglutaryl)

a gene codes for the mitochondrial version of HMG CoA synthase. this is a different gene than what codes for the cytosolic version used in cholesterol synthesis (where HMG CoA reductase acts on HMG CoA)

Question 12

name two ketone bodies useful for extrahepatic cells

what ketone body is produced more in liver cells during ketogenesis?

Answer 12

betahydoxybutyrate & acetoacetate

beta-hydroxybutyrate is produced more than acetoacetate

Question 13

name the enzyme:
betaketobutyrate <———-> beta-hydroxybutyrate

give reducing agent + oxidizing agent

Answer 13

betahydroxybutyrate dehydrogenase

• takes a ketone to an alcohol
• NADH is the reducing agent
• NAD+ is the oxidizing agent

Question 14

the fate of HMG CoA in liver mitochondria

Answer 14

In the mitochondrial matrix of liver cells for ketogenesis, HMG CoA lyase breaks HMG CoA into acetyl CoA and betaketobutyrate (4 carbon ketone molecule)

beta-hydroxybutyrate dehydrogenase catalyzes the oxidation of betaketobutyrate (a ketone) –> beta-hydroxybutyrate (an alcohol)

Question 15

describe the formation of acetone

Answer 15

forms from acetoacetate
non-enzymatic
acetoacetate loses its carboxyl group and turns into acetone

Question 16

is acetone useful as fuel? why or why not?

give fate of acetone in the body

Answer 16

no. has carbons but the cells have no ways to oxidize those carbons
body gets rid of acetone by moving it all over the body and eliminating it in sweat, urine, and mostly exhaled breath

Question 17

what happens in a person with very high levels of ketone bodies in the blood

Answer 17

likely will have acetone in their exhaled breath which may even be smelled on the breath