SYLLABUS 8: Fatty acid oxidation & ketone body production Flashcards
(38 cards)
what does oxidation of fatty acids provide
9 Kcal/g of energy
where are fatty acids important
major source of energy for most tissues; but not RBC or BRAIN
major storage form of energy, as triglycerides
where does out dietary fat come from
triglycerides, 3 fatty-acid esters of teh alcohol, glycerol
general chemical structore of a fatty acid?
CH3 - (CH2)n - COOH
structure of triglycerides?
glycerol backbone
3 fatty-acids in ester linkage
size of most fatty acids in our diet?
16 to 18 carbons
some contain double bonds in methylenes = unsaturated fatty acids - i.e. oleic acid
if >1 double bond, = polyunsaturated fatty acids, i.e. linoleic acid
what are fatty acids synthesized from
acetyl CoA
which came from pyruvate, which came from glucose
requires lots of energy to make fatty acids - NADPH - from pentose cycle, shuttles
what is the function of lipases in our diet?
what organs produce lipase?
what organs are involved w/ its action?
pancreas produces lipase;
lipase hydrolyzes dietary triglycerides to fatty acids + glycerol
bile salts from liver aid this
function of adipose tissue re: triglycerides?
fatty acids and glycerol are taken up by adipose tissue
triglycerides are resynthesized and stored largely in adipose tissue
functions of fatty acids?
- component of phospholipids & glycolipids of biological membranes
- major energy source for most tissues
- major storage form of energy as triglycerides
- produce signal transduction molecules, eg inositol phosphates, diacylglycerol
- produce prostaglandins and leukotrienes
when are fatty acids the main fuel for tissues?
in the fasted state
what activates or inactivates lipase? result re: fatty acids?
in the FASTED STATE: glucagon, epinephrine, norepinephrine activate lipase via cAMP-dependent PKA phosphorylation
in the FED STATE: insulin inhibits lipase by dephosphorylation
where does fatty acid oxidation take place?
mito & some peroxisomes
describe process of Fatty Acid oxidation in Mito and Peroxisomes, before B-oxidation
- glucagon, epi, or norepi activate the hormone-sensitive lipase by cAMP-dependent PKA phosphorylation
- activate lipase hydrolyses stored triglycerides to glycerol + fatty acids
- glycerol exits adipose tissue, goes to liver, enters gluconeogenesis or glycolysis at G3P & DHAP level
- fatty acids also can bind albumin in blood, transport to tissues; but albumin-fatty acid complex can’t cross blood brain barriers, so fatty acids do not reach brain for oxidation
- fatty acids are transported from albumin to fatty acid binding proteins for delivery inside the tissue
pathway of fatty acid oxidation?
B-oxidation pathway
once fatty acid is in the cell, how does it get into the inner mito membrane?
- fatty acid is brought to cell membrane by fatty acid binding protein
- fatty acid is activated to the fatty acyl CoA ester by acyl CoA synthase
this involves exchange of ATP + CoA for AMP + Pi
if short or medium chain acyl CoA synthase, fatty acid can directly enter the mito
if long, need a carnitine shuttle to enter
- carnitine shuttle converts long-chain fatty acyl CoA to long-chain fatty acyl carnitine
- long-chain fatty acyl carnitine enters the mito via carnitine translocase carrier
- in mito, fatty acyl carnitine interacts w/ carnitine transferase 1 or 2 to regenerate carnitine & fatty acyl CoA
- fatty acyl CoA undergoes B-oxidation
carnitine is shuttled out of matrix by carnitine translocase carrier, so it can do more carries of fatty acyl CoA into mito matrix
what fatty acids need carnitine shuttle? fxn?
brings fatty acids from long chain fatty acyl CoA synthases (>12 C) into the inner mito matrix
short or medium chain (4-8 C or 8-12 C) do not need carnitine shuttle
what is B-oxidation? products of it?
a series of 4 enzyme catalyzed reactions that acyl CoA undergoes
splits a 2C fragment of the acyl CoA to produce acetyl CoA + new fatty acyl CoA shortened by 2 C atoms
reaction produces 1 NADH and 1 FADH2 in steps 1 and 3 of the rxn
how long does the B-oxidation process continue for?
it’s a spiral, repeats until all the carbons are oxidized to acetyl CoA
each spiral produces 1 FADH2 and 1 NADH
how many times would an 18 C fatty acid undergo B oxidation?
products?
8 spirals
this produces 8 NADH, 8 FADH2, and 9 2C acetyl CoA products
how are odd chain fatty acids differently oxidized in B oxidation?
products are acetyl CoA (2C product) and propionyl CoA (3C product)
propionyl CoA undergoes 3 step metabolism reaction to become succinyl CoA
- propionyl CoA acted on by biotin produces D-Methyl malonyl CoA
- MMA epimerase acts on D-MM CoA, produces L-MM CoA
- MMA mutase, using B12, acts on L-MM CoA, produces succinyl CoA
what regulates the rate of B-oxidation?
1) availability of fatty acids via activated hormone-sensitive lipase
2) availability of **carnitine **
3) **malonyl CoA **is the rate-limiting step of fatty acid synthesis, inhibts carnitine acyl transferases 1 and 2
4) rate of the electron transport chain
what controls the availability of carnitine?
1) inborn errors of metabolism which lower carnitine synthesis
2) lysine synthesizes carnitine in mammals
how many ATPs are produced by B-oxidation of a C18 fatty acid?
8 NADH -> 20 ATP
8 FADH2 -> 12 ATP
9 acetyl CoA -> 90 ATP
- 2 ATP used to activate the fatty acid
= net ~120 ATP prouced
