4/13 ketogenesis

what are dietary sources of the unsaturated FAs?

triacylglycerols from plant oils

all naturally occurring unsaturated FAs have their double bonds in what configuration?

cis

what are the two groups of unsaturated FAs?

monosaturated and polyunsaturated

enoyl CoA is a mono-unsaturated FA with a cis double bond. because of this its oxidation requires an additional enzyme, what is the enzyme?

enoyl CoA isomerase

is enoyl CoA isomerase needed for the oxidation of saturated FAs?

no

does enoyl CoA isomerase require cofactors or ATP?

no

in poly-unsaturated FAs there are more than one cis double bond, what needs to happen because of this?

the cis is converted to trans

what is the first oxidation reaction to convert the cis to trans?

dehydrogenase which requires a reductase enzyme

what is the second enzyme needed for converting the cis to trans

3,2-enoyl CoA isomerase

what are reductases?

a group of enzymes that reduce a substrate by adding hydrogens. they need cofactors that act as the source of the hydrogen atoms to be donated

reductases have varied cofactor requirements, what ones do they usually use?

FADH2 or NADH

the ATP yield for polyunsaturated FAs is how many ATPs less than its saturated counterpart?

3 less

what are the dietary sources of FAs with an odd number of carbons?

dairy products, nuts and sea weeds

FAs with an odd number of carbons are oxidized the same way as their even counterparts up until the very last oxidation cycle where we start with a 5 carbon fragment. what happens here?

the thiolase enzyme splits this five carbon fragment to two different products, an acetyl CoA molecule and propionyl CoA

where does the acetyl CoA go?

to feed the citric acid cycle

where does the propionyl CoA go?

also feeds into the citric acid cycle but not directly, it is first converted to succinyl CoA which then enters the cycle

propionyl CoA is converted to succinyl CoA in multiple steps

yay

what is the first step in converting propionyl CoA to succinyl CoA

addition of a carboxyl group to propionyl CoA to get the S isomer of methyl malonyl CoA. this is a carboxylation reaction

enzymes that catalyze carboxylation reactions are called what?

carboxylases

step 1 of this reaction is catalyzed by what enzyme?

propionyl CoA carboxylase

what do carboxylases do?

add a carboxyl group to their substrates

carboxylases require two cofactors which are?

an ATP molecule and a molecule of biotin (B7)

what is the second step in the process of converting propionyl CoA to succinyl CoA

S-methylmalonyl CoA is isomerized to the R isomer by the enzyme racemase

what are racemases?

enzymes that interconvert between the R and S isomers of chiral molecules

does racemase require cofactors or ATP?

no

what is the third step of converting propionyl CoA to succinyl CoA?

R-methylmalonyl CoA is converted to succinyl CoA by the enzyme mutase

what are mutases?

enzymes that shift functional groups from one carbon to a directly adjacent carbon

mutase requires what cofactor?

cyanocobalamine, vitamin B12

what do vitamins B7 and B12 do?

allow us to utilize FAs with an odd number of carbons for energy production

how much ATP does succinyl CoA produce in the citric acid cycle?

6 ATP

all FAs with an even number of products only give what end product?

acetyl CoA

FAs with an odd number of carbons give what products?

acetyl CoA and propionyl CoA

some oxidation cycles of unsaturated FAs are longer than for saturated ones, why is this?

becuase they require more enzymes to process their double bonds

if there is only one double bond, how many additional enzymes are needed?

one

if there is more than one double bond, how many additional enzymes are needed?

three

riboflavin or vitamin B2 makes what?

FAD

niacin or nicotinic acid or vitamin B3 makes what?

NAD

biotin or B7 is the cofactor for what?

carboxylases group of enzymes

cyanocobalmin or vitamin B12 is the cofactor for what?

different types of enzymes

brain cells can not oxidize FAs to acetyl CoA, why?

because they do not make the enzymes needed

what do brain cells use to make acetyl CoA?

ketone bodies

what happens to the brain if neither ketone bodies or glucose is available

it shuts down and the person goes into a coma

what is ketogenesis?

the group of reactions that occur when glucose levels drop. its purpose is to provide ketone bodies for brain cells to maintain the citric acid cycle and make ATP

where does ketogenesis occur?

in the mitochondria of liver cells

ketone bodies are only made by what?

the liver

are ketone bodies basic or acidic?

acidic

what happens if ketone bodies are released into circulation in large amounts?

they can overwhelm blood buffers and cause severe systemic acidosis

what is the first reaction of ketogenesis?

a condensation reaction where two molecules of acetyl CoA are combined to give acetoacetyl CoA

the condensation reaction is catalyzed by what enzyme?

thiolase

is thiolase reversible or irreversible?

reversible

what determines which direction the thiolase reaction may proceed?

the concentration of the reactants and products

if there is little acetyl CoA in cells, where does the reaction proceed?

towards breaking down the FA chain to acetyl CoA

if acetyl CoA starts to accumulate, where does the reaction proceed?

backwards towards making acetoacetyle CoA

what is the second reaction of ketogenesis?

a condensation reaction where a third molecule of acetyl CoA is added to acetoacetyl CoA by the enzyme HMG CoA synthase to produce HMG CoA

what are the two things to remember about this reaction?

1. it is a condensation reaction that does not require ATP. this is why enzyme needed is a synthase

2. the complete name is HMG CoA synthase and it is a liver enzyme

what is the third reaction of ketogenesis?

the enzyme HMG CoA lyase splits HMG CoA to acetyl CoA and acetoacetate

where is the acetoacetate release?

part into the circulation for the brain to absorb and utilize and part remains in the liver where it gets reduced by the enzyme beta-hydroxybutyrate dehydrogenase to give beta-hydroxybutyrate that gets release into circulation

in circulation, a small amount of the released acetoacetate undergoes what?

spontaneous decaroxylation to give acetone (the third ketone body)

the other two ketone bodies are what kind of molecules?

acidic and are soluble in plasma and excreted in urine

what do high plasma/urine levels of ketone bodies indicate?

a shift in metabolism to oxidizing FAs

what is the reason for making ketone bodies for the brain?

to convert them to acetyl CoA

all cells in the body, particularly brain cells make what?

the enzyme beta-hydroxybutyrate dehydrogenase which converts beta-hydroxybutyrate to acetoacetate

is this reaction reversible or irreversible?

reversible

acetoacetate is converted to acetoacetyl CoA via what enzyme?

ketoacyl CoA transferase

what is important to note about ketoacyl CoA transferase?

it is made by brain and all other tissues except the liver. this way all tissues can convert ketone bodies to acetyl CoA except the liver

ketoacyl CoA transferase requires what to be present to catalyze this reaction?

succinyl CoA

what does this reaction produce?

acetoacetyl CoA and succinate

where does the succinate go?

into the citric acid cycle

where does the other product, acetoacetyl CoA, go?

it is broken down by thiolase enzyme to two acetyl CoA molecules

how much acetyl CoA is produced from one ketone body?

only two

in diabetes patients, they cannot utilize glucose for energy production and instead oxidize FAs. however, the brain cannot oxidize FAs so it relies on what?

the liver to convert those FAs to ketone bodies

this causes diabetic patients to have higher than normal levels of what?

ketone bodies

high ketone bodies and can result in keto acidosis which does what?

impairs the oxygen carrying capacity of hemoglobin which diminishes the amount of oxygen reaching the brain causing it to shut down and the patient to go into a coma