unit 13: lipids and fatty acid catabolism

1. building blocks of phospholipids and glycolipids

2. modification of proteins to target them to their appropriate membrane locations

3. derivatives can serve as hormones and intracellular messengers

4. as a source for energy

what are the physiological functions of fatty acids?

unsaturated

has at least one double bond

monounsaturated

has one double bond

polyunsaturated

more than 1 double bond

saturated

no double bonds are there

glycerol

what makes up the backbone of fatty acids?

cis

unsaturated fatty acids are usually int eh BLANK position

saturated fatty acids

-very tightly packed

are unsaturated or saturated fatty acids more stable?

triglycerides (triacylglycerols)

fatty acids are stored as BLANK

because they are reduced and anhydrous

-allows for multiple redox reactions and the generation of lots of NADH, FADH2/ATP

why are triglycerides a highly concentrated energy source?

-start numbering at the double bond

-the end is omega (w)

-the carbon next to the end is w-1, then it goes on (w-2, w-3, w-4, etc.)

nomenclature for fatty acids

12: # of carbon atoms

0: # of double bonds

(Δ9): double bond between carbon 9 and 10

what does each part mean?

12:0 (Δ9)

- 16:0

-saturated

palmitic acid:

- 18:0

-saturated

stearic acid:

-16:1 (Δ9)

-unsaturated

palmitoleic acid:

an even number of carbon atoms

most naturally occurring fatty acids have:

rarely conjugated (usually 3 carbons apart)

double bonds in fatty acids normally occur in the same positions and are...

-diet

-triglycerides store in cells as lipid droplets

-fats synthesized in one organ for export to another

cells can obtain fatty acids from 3 sources:

fatty acids generate more ATP per molecule than a molecule of glucose

the heart prefers fatty acids opposed to glucose. what is the advantage of this?

lipase

-cleaves fatty acids from triglycerides

-produces free fatty acids (FFA)

VLDL

LDL

HDL

what does the liver make?

lipoproteins (chylomicrons, VLDL, LDL, HDL)

in order to be transported within the blood, triglycerides and cholesterol are solubilized through association with macromolecular aggregates known as:

chylomicrons

primarily comprised of triglycerides with some cholesterol

adipose tissue

primarily storage

-stored as a triglyceride

muscle

stored or used for energy

glucagon

BLANK triggers mobilization of stored triglycerides

1. low levels of glucose triggers release of glucagon which bind to receptors

2. protein kinase A (PKA) is activated

3. PKA phosphorylates hormone-sensitive lipase and perilipin molecules

4. phosphorylation alters conformation of perilipins and allows access of the hormone sensitive lipase

5. triglycerides are hydrolyzed to free fatty acids via steps 5-8

6. free fatty acids leave and bind to serum albumin

7. albumin transports fatty acids to myocytes where they enter a transporter

8. fatty acids undergo beta-oxidation to produce needed ATP

6 steps of glucagon triggering the mobilization of triglycerides

perilipins

coats lipid droplets and restricts access

conversion to dihydroxyacetone phosphate

glycerol can enter glycolysis via...

First: kinase

-ATP to ADP

-glycerol to glycerol 3-P

Second: dehydrogenase

-NAD+ to NADH

-glycerol 3-P to dihydroxyacetone phosphate

what 2 enzymes are needed to take glycerol to dihydroxyacetone phosphate?

1.5 ATP

-cost: ATP

-gain: NADH (2.5 ATP)

the transformation of glycerol to dihydroxyacetone phosphate had a net yield of...

18.5 molecules

how much ATP is produced per molecule of glycerol?

isomerase

what enzyme can be used to take dihydroxyacetone phosphate back to Gly 3-P?

17 ATP

how much ATP is produced per one molecule of Gly 3-P?

fatty acid activation via coenzyme A

what process always precedes any oxidation?

-2 step process that involves high energy bonds

1. hydrolysis

2. produce energy

3. move rxn in the forward direction

what are the 3 purposes of pyrophosphate (PPi)?

2 ATP -> 2 ADP + 2Pi

what is the total cost of fatty acid activation?

activated: outer mitochondrial membrae

oxidized: inner mitochondrial matrix

where are fatty acids oxidized and activated?

move fatty acids into mitochondria

-required bc the membrane is otherwise impermeable

what is the purpose of carnitine?

translocase

enzyme in the inner mitochondrial membrane that transports the fatty-acid carnitine combo across the membrane

step 1: acyl-CoA dehydrogenase

-redox rxn, NADH or FADH2 is formed

step 2: enoyl coA hydratase

-adds H2O

step 3: beta-hydroxyacyl-CoA dehydrogenase

step 4: acy-CoA transferase (thiolase)

-breaks bonds with sulfhydral groups (thiol or thio group)

-hydrolysis

4 steps of beta oxidation of fatty acids

FADH2

NADH

what are the 2 products formed from step 1 and then step 3 of fatty acid oxidation?

stereospecific

-only one isomer forms

-trans isomer

steps 1 and 2 of fatty acid oxidation are very...

is it shortened by 2 carbon atoms

During step four of fatty acid oxidation, what happens to the fatty acid so that is can enter another round?

1 FADH2, 1 NADH, 1 acetyl CoA form

fatty acid shortens by 2 carbon atoms

In each round of beta oxidation, the following events occur:

thiolase turns a C4 fatty into 2 acetyl CoA

In the final round of B-oxidation, what happens?

x/2 -1

x= # of carbon atoms in a fatty

how do you calculate the number of rounds?

7 rounds

-7 FADH2 x 1.5 ATP = 10.5 ATP

-7 NADH x 2.5 ATP = 17.5 ATP

-8 acetyl coA x 10 ATP = 80 ATP

total = 108 atp - 2 atp (activation cost) = 106 ATP

how many rounds would there be for a C16 fatty acid? and calculate the ATP

beta oxidation

metabolism of unsaturated fatty acids occurs by...

-use an isomerase instead of a dehydrogenase in step 1

-NO FADH2 formed (1.5 ATP not formed)

metabolism of an unsaturated fatty acid with an odd number of double bonds

-insert 2 enzymes between steps 1 and 2

-FADH2 is formed in step 1

-reductase (first) and isomerase (second) are used

metabolism of an unsaturated fatty acid with an even number of double bonds

-initially calculate as if there are NO double bonds

-add deductions to calulate final ATP

---subtract 2 ATP (activation cost)

---subtract 1.5 ATP (for the 1 odd # double bond)

what happens when an unsaturated fatty acid has one off and one even double bond?

-thiolase is used

-propionyl coA is produced but converted to succinyl coA

-acetyl coA forms and you get 10 ATP

for fatty acids with an odd number of carbons (rare), the final step of beta-oxidation ...

the rate of transfer into the mitochondrial matrix

the pathway for fatty acid oxidation depends upon:

the 3-step carnitine shuffle

-moves acetyl coA into the matrix

what is the rate-limiting process for fatty acid metabolism:

malonyl-coA

-leads to inhibition of carnitine acyltransferase I

what increases when excess glucose is present?and what does this lead to?

Beta-hydroxyacyl-CoA dehydrogenase

thiolase

what are the 2 enzymes within the Beta-oxidation pathway?

NADH/NAD+ ratio is high

-this signals an increase in capacity to make ATP so no more beta-oxidation is needed

Beta-hydroxyacyl-CoA dehydrogenase is inhibited when:

acetyl coA concentration increases

thiolase is inhibited when:

phosphatase

(and storage)

when there's high BG, insulin is produced and stimulates:

kinase

(ACC shuts off)

when there's low BG, glucagon is produced and stimulates:

acetyl coA carboxylase

-adds a carboxylic acid and converts acetyl coA to malonyl coA

-requires biotin (CO2 carrier)

what is ACC?

oxaloacetate is present

the acetyl coA formed in fatty acid oxidation can enter the citric acid cycle only if:

fats provide acetyl coA

carbs provide oxaloacetate

what do fats and carbohydrates provide?

oxaloacetate

-it is actually shunted to gluconeogenesis

during periods of poorly controlled diabetes or starvation, there is an insufficient supply of BLANK because...

ketone bodies

during periods of poorly controlled diabetes or starvation, acetyl coA is diverted to form...

D-3-Hydroxybutyrate

what is considered the "Dead end" int he formation of ketone bodies?

-water soluble carriers of energy that are transported in the blood

-alternative energy sources for extrahepatic tissues

-major fuel source for brain when in periods of starvation/bad diabetes

what are the normal functions of ketone bodies?

heart muscle

renal cortex

both the BLANK and BLANK use acetoacetate in preference to glucose.

glucose exported as fuel for brain and other tissues

step 1 when ketone bodies are overproduces in poorly controlled diabetes and starvation

ketone bodies exported as energy soruce for ehart, skeletal muscle, kidney, and brain

step 2 when ketone bodies are overproduces in poorly controlled diabetes and starvation

acetyl-CoA

during starvation, gluconeogenesis depletes citric acid cycle intermediates; therefore diverting BLANK to ketone body production

-extrahepatic tissues cannot efficiently take up glucose in blood

-levels of malonyl-CoA decrease and inhibition of carnitine acyltransferase I is removed

-increases metabolism of fatty acids by beta-oxidation, but ability to enter CAC is compromised

--leads to increase in ketone bodies in blood

key points when insulin levels are insufficient in untreated diabetes

acidosis (or ketoacidosis)

-these conditions can lead to coma or death

increase in ketone bodies in the blood leads to...