Lipid Metabolism

triaglycerols

these are responsible for 1/3 of our dietary needs

a glycerol head with 3 fatty acid chains attached

80%

fatty acid oxidation meets this percent of energy needs in the mammalian heart and liver

hibernate

animals that do this rely extensively on fat

more energy since more reduced, less water since non-polar

advantages of fats over carbohydrates

long term energy needs, storage, and slow delivery

three characteristics of fats in relation to the glucose/glycogen for quick delivery

interfacial activation

The increase in activity when a lipid-specific enzyme contacts the lipid-water interface.

property of lipases and phospholipases, which are soluble enzymes but must break down an insoluble material

lipid-water interface

location where lipid emulsification takes place:

bile from the liver helps emulsify the fats, the increases surface area from emulsification increases this, which then enhances the rate of lipid digestion

surface area

this of the lipid-water interface is the main factor for the rate of the lipid digestion reaction

increase emulsification with bile acids, peristaltic movement of the small intestine

ways to increase surface area of lipid-water interface

peristaltic movement

Contractions of circular muscles in anterior end lengthen the body pushing the anterior end forward

helps allow more thorough mixing of fats with bile and digestive enzymes

chylomicrons

take dietary triaglycerols from intestine to muscle as well as dietary cholesterol from intestine to liver

intestine to muscle

chylomicron transfer path for dietary triacylglycerols

intestine to liver

chylomicron transfer path for dietary cholesterol

dietary fats to storage pathway

1) Bile salts emulsify dietary fats forming miscelles

2) Intestinal lipases degrade triacylglycerols

3) FA and other products taken up by intestinal mucosa and converted to triaclyglycerols

4) Chylomicrons get incorporated with chyomicrons, along with cholesterol and apolipoproteins

5) Chylomicrons move through the lymphatic system

6) Lipoportein lipase is active in capillaries and breaks down triaclyglycerols into fatty acids and glycerol

7) Fatty acids used as fuel or storage in the cells

High-density lipoprotein (HDL)

good cholesterol - moves triaclyglycerols and cholesterol from the tissues to the liver

very low density lipoprotein, low density lipoprotein, intermediate density liporprotein

transport triaclyglycerols and cholesterol from the liver to the tissues

pancreatic lipase

catalyxes fat hydrolysis at the 1 and 3 positions

enzymatic activity increases with increased lipid-water interface interactions

serine protease

phospholipase a2

enzyme that converts a phospholipid into a lysophospholipid - has carboxyllic acid byproduct

phospholipid + h2o --> lysophospholipid + carboxyllic acid

net reaction for the phospholipase reaction

fatty acid binding protein

Proteins that bind to fatty acids and enable them to be transported into cells.

increases the intestinal absorption of lipids - process takes place in the liver and the kidneys

Adipocytes

fats are stored here, triggered by hormone sensitive lipases

Hormone --> adenylate cyclase activated --> cAMP --> protein kinase --> triacylglycerol lipase --> dicylglycerol (from tricylglycerol) --> other lipases turn: glycerol + fatty acids released into blood stream

hormone cascade to release fatty acids from adipocytes

albumin

fatty acids bind to this to increase their solubility and increase their absorbtion into cells once stimulated to be released from adipocytes

beta oxidation

A metabolic sequence that breaks fatty acids down to two-carbon fragments that enter the citric acid cycle as acetyl CoA.

Knoop's experiment

proved beta oxidation:

for odd chain fatty acid had benzoic acid was breakdown product and hippuric acid as excretion product

for even chain fatty acid had phenylacetic acid as breakdown product and phenylaceturic acid as excretion product

benzoic acid and hippuric acid

breakdown and excretion product of Knoop's experiment for an odd chained fatty acid

pheylacetic acid and phenylaceturic acid

breakdown and excretion product for Knoop's experiment for an even chained fatty acid

Lehninger's experiment

showed that a rat liver needed and input of ATP to have FA metabolism

hence FA metabolism needs activation

acyl co-A

this product activates fatty acid breakdwon - can be used for fatty acids that are 2-16 carbons in length

formed in the cytosol

2-16

length limit for carbon chains with acyl co-A synthetase

Acyl Co A Synthetase

enzyme that converts fatty acid to acyl-coA through three main steps in the cytosol

Fatty acid + ATP --> PPi + Acyladenylate mixed anhydride

PPi + H2O --> 2Pi

CoASH + Acyladenylate mixed anhydride --> Acyl-coA and AMP

acyl coA and AMP

2 main products of the acyl co a synthetase reaction

fatty acid + coash + atp --> acyl coA + amp

net reaction of acyl coA reaction

cytosol

intracellular location of the acyl-coA synthetase reaction

carnitine

a nonessential, nonprotein amino acid made in the body from lysine that helps transport fatty acids across the mitochondrial membrane

acyl-carnitine

Acyl-CoA molecules are translocated into the mitochondria as what molecule? This molecule is formed after the reaction with acyl CoA and carnitine

acyl CoA + carnitine <--> acylcarnitine + CoA

reaction by carnitine palmitotransferase in the cytosol and the mitochondrial matrix

carnitine palmitoyltransferase

Enzyme facilitating fatty acid transport into mitochondria.

Two types: carnitine acyltransferase 1 and carnitine acyltransferase 2

net reaction is:

1) acyl CoA + carnitine --> acylcarnitine + CoA at acyltransferase

2) crosses mitochondrial matrix through transporter

3) acylcarnitine + CoA <--> acyl CoA + carnitine in matrix, at carnitine acyltransferase 2

1) Beta-oxidation: acetyl coA, NADH, FADH2

2) TCA: ATP, NADH, FADH2

3) ETC: ATP

3 stages to fatty acid oxidation and their products (in terms of energy)

acyl co-A dehydrogenase

converts:

FA-acyl CoA + FAD --> FADH2 + trans-delta-2-enoyl coA

FA-acyl CoA + FAD --> FADH2 + trans-delta-2-enoyl coA

acyl co-A dehydrogenase net reaction

transdelta 2 enoyl co A

product of the acyl co-A dehydrogenase net reaction along with FADH2

Enoyl Co-A hydratase

carries of the net reaction that oxidizes the beta position

trans-2-enoyl co-A + H2O --> 3,1-hydroxyacyl-coA

3,1-hydroxyacyl-coA

product of the Enoyl Co-A hydratase net reaction

3,1-hydroxyacyl-coA dehydrogenase

carries out this reaction:

NAD+ + 3,1-hydroxyacyl-coA --> NADH + beta-ketoacyl-coA

beta-ketoacyl-coA

product of the 3,1-hydroxyacyl-coA dehydrogenase net reaction

NAD+ + 3,1-hydroxyacyl-coA --> NADH + beta-ketoacyl-coA

net reaction of the 3,1-hydroxyacyl-coA dehydrogenase reaction

beta-ketoacyl thiolase

last step in one round of beta oxidation:

beta-ketoacyl-coA + CoASH --> acetyl-coA + FA-CoA

Fatty acid is not two lengths shorter

ACAD (acetyl-coA) dehydrogenase

MADD disease biochemical basis

MADD disease

multiple acyl-coA dehydrogenase deficiency

caused by acetyl-coA dehydrogenase (ACAD) deficiency

cannot process FA appropriately to get energy

riboflavin

treatment for late onset MADD - as stimulates energy releasing pathways

mcad (medium-chain acyl-coA dehydrogenase)

deficiency in this enzyme leads to 10% of deaths in SIDS (sudden infant death syndrome)

8 acetyl-coA, 7 NADH, 7 FADH2

is 16 carbon fat will undergo how many around of beta oxidation, product how many FADH2, NADH, and acetyl-coA

1 NADH, 1 FADH2, 1 acetyl-CoA

every turn of the fatty acid cycle produces ___

except the last round which makes 2-acetyl co-A

exergonic

fatty acid synthesis is highly this

129 ATP

net energy gain for complete fatty acid oxidation of a 16 C carbon

recall acyl coA requires 2 ATP

cis

naturally occurring unsaturated fatty acids have theset ype of double bonds and therefore cannot be substrate for enoyl-coA hydratase

isomerase and reductase

two additional enzymes required for beta oxidation of cis-unstaurated fatty acids

2,4 dienonyl reductase

this enzyme involved in cis-unsaturated fat synthesis reduces bonds not at carbon 3

used only by polyunsaturated fats

uses NADPH to have only 1 FADH2 loss

have a 2,3 trans bond and a 4,5 cis bond - converts to 3,4 trans bond with NADPH

isomerase then converts back to 2,3 cis-bond so beta oxidation can continue

delta 3, delta 2 enonyl isomerase

this enzyme involved in cis-unsaturated fatty acid synthesis converts cis double bonds to trans double bond at carbon 3

mono-unsaturated fatty acids only need this

also used by polyunsaturated fats

1 FADH2

cost of using isomerase in beta oxdiation of a cis unsaturated fatty acid

double bond must be between 2 and 3 position

acyl co A dehydrogenase step is skipped

3 and 4

cis double bond must be between these two positions for the isomerase to work

now have a double bond between positions 2 and 3 that is trans

nadph

used by reducatase in polyunsaturated fatty acid synthesis to make trans double bond at 3,4 position - started with DB at the 4,5 position and 2,3 position