ochem 24 metabolic pathways for lipids and amino acids

where is fat stored in the body

where is fat stored in the body

adipocytes

fat cells (adipocytes) store how much fat and in what form

unlimited and in the form of triacylglycerides

adipose tissue stored ___% of energy available in the body

85

where does digestion of fats begin

small intestines

role of bile salts in digestion of fats

emulsify the fat globules into smaller particles called micelles in the small intestines

pancreatic lipases role in digestion

after bile salts emulsify the fat glubules into miccelles, pancreatic lypases hydrolyse ester bonds to form monoglycerols and free fatty acids which are small enough to be transported into the cells of the intestinal lining

what occurs to the monoglycerols and free fatty acids in the intestinal lining

they recombine into tryacylglycerols

once triacylglycerols are in the intestinal lining, what occurs to them

phospholipids and proteins coat the fats, forming chylomicrons, which are transported to the cells of heart, muscle, and adipose tissues.

in the cells of the heart, muscle, and adipose tissue, what do lipases do

lipases hydrolyze triacylglycerols, forming glycerol and free fatty acids, which are oxidized to acetyl CoA molecules for ATP synthesis.

overall digestion of fats

in reference to fat, when blood glucose is depleted and glycogen stores are low

the process of fat utilization is stimulated.

when fat utilization is stimulated, what hormones are released and what do they do

•the hormones glucagon and epinephrine are secreted into the bloodstream, where they bind to receptors on the membrane of adipose tissue.

when glucagon and epinephrine are secreted into bloodstream, they activate what

hormone sensitive lipase

what does hormone-sensitive lipase do

within the fat cells catalyzes the hydrolysis of triacylglycerols to glycerol and free fatty acids

what happens to the glycerol and free fatty acids made from hydrolysis of the triacylglycerol

•diffuse into the bloodstream and bind with plasma proteins to be transported to the tissues, muscles, and fat cells.

how to we metabolize glycerol

it is converted into dihydroxyacetone phosphate into 2 steps

• uses ATP to give P to glycerol which turns it into glycerol-3-p

• glycerol-3-p is oxidized at its -OH group into dihydroxyacetone phosphate (uses NAD+—> NADH)

  • this can then go into glycolysis or gluconeogenesis

in the metabolism of glycerol how many ATP used and how many NADH are made

1 ATP in the first step to form glycerol-3-p

1 NADH in the second step to form dihydroxyacetone phosphate

in the metabolism of glycerol, what do we end up creating

dihydroxyacetone phosphate, which is an intermediate in glycolysis and gluconeogenesis.

what is beta-oxidation

the catabolic reaction that breaks down a fatty acid by removing two-carbon segments containing the alpha and beta carbon from the carboxyl end of the fatty acid

what hormone activates beta oxidation

glucagon (wants energy in the bloodstream so wants us to break down fat molecules to make ATP)

a cycle of beta oxidation produces what (compounds)

acetyl CoA and a FA that is 2C’s shorter than it was

how many cycles does a fatty acid go through in beta oxidation

repeats until the original FA is completely degraded into 2-C units that form acetyl CoA to enter the citric acid cycle

where in the cell do we find fatty acids

cytosol

where does beta oxidation take place in

matrix of mitochindria

what must happen to the FA before beta oxidation can occur (not location)

it is combined with HS-CoA to yield high energy fatty acyl CoA (ACTIVATED)

what does the activation of a FA for beta oxidation use

- uses ATP to use the energy from the hydrolysis of it to AMP

- has HS-CoA added to FA

what is the activated form of a fatty acid

fatty acyl CoA (fatty acid with a CoA)

how does the fatty acid get from the cytosol to the mitochondrial matrix

it uses the carnitine shuttle where the fatty acyl group is transferred to the hydroxyl group of carnitine to produce fatty acyl carnitine which can pass through the inner mitochondrial membrane into the matrix

once in the mitochondrial matrix, how do we get fatty acyl CoA again

- then when in the mitochondria a reverse reaction occurs where the fatty acyl group is transferred to CoA to reform fatty acyl CoA

what is the carnitine shuttle

how a fatty acyl can get from the cytosol into the mitochondrial matrix.

- Fatty acyl CoA has its fatty acyl group is transferred to the hydroxyl group of carnitine to produce fatty acyl carnitine which can pass through the inner mitochondrial membrane into the matrix

- then when in the mitochondria a reverse reaction occurs where the fatty acyl group is transferred to CoA to reform fatty acyl CoA

beta oxidation has how many reactions

4 reactions in each cycle

in each cycle of beta oxidation, what is produced

- 1 NADH

- 1 FADH2

- 1 fatty acid chain that is 2C’s shorter

why is it called beta oxidation?

because you end up breaking the bond between the beta and alpha carbon of the fatty acid chain, and these 2 carbons undergo a series of oxidation reactions that end up producing NADH and FADH2

when re usually refer to beta oxidation, we are referring to what kind of fatty acids

saturated fatty acids (no double bonds)

beta oxidation reactions

1.fatty acyl CoA is oxidized to form a trans C=C bond between the alpha and beta carbon, producing FADH2 (fatty acyl Coa—> trans-enoyl CoA)

2.trans-enoyl Coa is then hydrated to break the = bond and add an OH to the beta carbon (trans-enoyl CoA —> 3-hydroxyacyl CoA)

3.3-hydroxyacyl CoA is oxidized to have the OH on the beta carbon become a carbonyl (c=o) group, producing NADH (3-hydroxyacyl CoA—> beta-ketoacyl CoA)

4. beta-ketoacyl CoA then split between the beta and alpha carbon, forming a fatty acyl CoA that is 2 carbons shorter (and has CoA added to it) and an acetyl CoA

how do you know how many cycles a fatty acid goes through

•The number of carbons in a fatty acid determines the number of times the cycle repeats and the number of acetyl CoA units it produces.

The total number of times the cycle repeats is one fewer than the total number of acetyl groups it produces.

what about off numbered fatty acids

-go through the same 4 steps of beta oxidation

BUTTTTT

-in final cycle, the remaining fatty acyl CoA is cleaved to yield a propionyl CoA (C₃) group and an acetyl CoA (so a 3 carbon molecule and a 2 C molecule)

what type of fatty acids does normal beta oxidation occur with

saturated (no = bonds)

how does beta oxidation of unsaturated fatty acids differ from that of saturated

they have one or more cis double bonds so

•before starting oxidation, an isomerase converts a cis double bond to a trans double bond between the α and β carbons (moves the = bond to be between the α and β C’s and makes it trans) so the fatty acid can undergo hydration.

•It forms a product that enters β oxidation at reaction 2, so the energy released by the β oxidation of an unsaturated fatty acid is slightly less because no FADH₂ is produced in that cycle—→ so no FADH made in every cycle that had a cis double bond)

when we have a unsat fatty acid undergo beta-oxidation, what outcome is different

for every = bond, no FADH is made in that cycle it is involved in

-so if we have a 18:1, this undergoes 8 cycles and instead of 8FADH being made like in 18:0, only 7FADH are made)

how many acetyl coA are formed for a fatty acid

-if even number, ½ amount of carbons

-if odd numbered, ½ amount of C minus 1 (last cycle)

how many cycles does a fatty acid undergo in beta oxidation

1 less than the amount of fatty acids made; 1 less than ½ the amount of carbons

-if we have a 16C FA, it makes 8 acetyl Coa, so it goes through 7 cycles

activation of fatty acid uses how many ATPs

2

NADH makes how many ATP molecules

2.5

FADH makes how many ATP

1.5

acetyl CoA goes where

the citric acid cycle

1 cycle of the citric acid cycle makes how many ATPs

10 ATPs

so how do we calculate total ATP production for beta oxidation of a fatty acid

-2 ATP from activation

10x # of acetyl Coa made

2.5 x # NADH made

1.5 x #FADH2 made

then add all these and you get your total ATP

when we do not have carbohydrates available to break down for energy, what do we use instead

fatty acids

what do fatty acids break down to

acetyl coA

can acetyl coA be made into pyruvate

NO

so what do with the acetyl coA formed by the oxidation of fatty acids

combine them to form ketone bodies

why do ketone bodies form?

because when we have to much acetyl coA produced due to the oxidation of fatty acids, it acculates in the liver because the citric acid cycle cannot process ot fast enough, so they combine through ketogenesis to form ketone bodies

what is ketogenesis

the pathway where acetyl coA compounds combine to form ketone bodies

how many reactions are in ketogenesis

4 reactions

how ketogenesis begin

2 acetyl CoA’s combine to form acetoacetyl coA by losing 1 coA (condensation)

- reverse to last step of beta oxidation

once we have acetoacetyl CoA,

we hydrolyze it by removing the CoA and form acetoacetate

acetoacetate can then become what

it can either become beta hydroxybutarate by being reduced (by NADH+) OR

it can be decarboxylated to yield acetone (and CO2)

-both of these possible products are ketone bodies

in ketogensis we begin with

2 acetyl CoA’s

in ketonegenesis we end with

a ketone body,

-either beta-hydroxybutyrate through reduction by NADH+

-or acetate by losing a carbon as CO2

what is ketosis

high accumulation of ketones (which are acidic) causes blood pH to be below 7.4

-occurs with diabetes, high fat diets, and starvation

what is diabetes (insulin, glucose, effect on fats)

when insulin does work properly and glucose levels are not enough for energy needs, so fats are used instead and broken down to acetyl COA in whcih the buildup activates ketogensis to produce ketone bodies

type 1 vs type 2 vs gestational

-type 1 is usually seen start in children and is when pancreas does not make enough insulin due to mutation or viral infection

-type 2 is usually seen in adults and is when insulin is made but the insulin receptors are not responsive

-gestational occurs during pregnancy but blood glucose levels go back to normal after baby is born

in diabetes, insufficient amounts glucose causes liver cells to

make glucose through gluconeogenesis which increases levels of acetyl coA —> ketogenesis—> ketosis

when we have consumed enough energy and our glycogen stores are full, the acetyl coA from breakdown of carbs and FAs is used

to make FAs in the cytosol

fatty acid synthesis is also called

lipogenesis

lipogenesis primarily makes what fatty acid

16 carbon, saturated FA: palmitic acid

how does fatty acid synthesis work (big picture)

linking acetyl groups to form a 16-C FA (palmitic acid) by adding 2-carbon acetyl units to growing chain

is the synthesis of fatty acids the reverse of beta oxidation

NOOOOOOO

- different location (cytosol vs mitochondrial matrix)

-different coenzymes (NAPDH vs FAD and NAD+)

-different enzymes

what do we link together in fatty acid synthesis (the goal of each cycle)

add a acyl group to the growing acyl chain

what FA do we usually produce through this

palmitate (16 C’s)

what must occur before FA synthesis can begin

the acyl compounds that will be added MUST BE ACTIVATED into activated carriers

how is an acyl compound activated

an acyl carrier protein (HS- ACP) binds to it

acyl carrier protein

HS- ACP

-similar to CoA (aminoethanethiol, pantothenic acid, and phosphate) but has a protein attached to the protein

-binds to the acyl compound to make it into an active carrier

what 2 compounds do we need to activate with ACP?

acetyl CoA and malonyl CoA

malonyl CoA is not already synthesized in the body so how do we make it

acetyl coa + bicarbonate —> malonyl CoA

- uses 1 ATP

what do malonyl CoA and Acetyl CoA turn into when activated

malonyl CoA—> malonyl ACP

acetyl CoA—> acetyl ACP

how many reactions are in synthesis of FA’s

4 reactions

where does synthesis of FA’s occur

cytosol (so anaerobic)

in FA synthesis what do you begin with (what compound)

acetyl CoA (which is then turned into acetyl ACP and combined with malonyl CoA)

what is used for fatty acid synthesis

NADPH

lipogenesis steps

-acetyl ACP and malonyl ACP are combined to form acetoacetyl ACP by malonyl ACP losing a carbon and acetyl CoA losing ACP, which releasing CO2 and a ACP

-acetoacetyl ACP is reduced to 3-hydroxyacyl ACP, making NADP+

-3-hydroxyacyl ACP is then dehydrated (loses H2O) to make trans-2-enoyl ACP (so loses water and forms a = bond between those carbons)

-trans-2-enoyl ACP is reduced into butyryl ACP (no c=c bond) which is 2 C’s longer, and NADP+ is made

-then cycle repeats by adding in a malonyl ACP and then repeating the steps to make if longer

how many cycles occur in fatty acid synthesis

-most of the time the FA made is palmitate which has 16 C’s, so the cycle repeats 7 times

-if we need to make shorter chains it will just stop earlier

-if need longer it will continue but with with special enzymes to add the C’s as this process is only for up to 16 Cs

in cycle 2, what do we end up making

hexanoyl ACP

at the end of lipogenesis, what do we do with palminoyl ACP

hydrolyse the ACP off to make palmitate

what are the 4 reactions we see

1. condensation

2. reduction

3. dehydration

4. reduction

in making malonyl Coa (needed to make malonyl ACP) what do we need

1 ATP used

for each cycle of fatty acid synthesis, what do we make/ use

- use 2 NADPH

-make FA that is 2C longer

in the fatty acid synthesis of palmitate, what do end up producing/ using

-use 8 acetyl CoA, use 14 NADPH, and 7 ATP

-make palmitate, 14 NADH+, 7 ADPs (and release 8 CoA)

if we need to make shorter FA chains (< 16C’s)

•shorter fatty acids are released earlier in the fatty acid synthesis process before there are 16 carbon atoms in
the chain.

how is FA synthesis regulated?

by insulin

if we need to make longer FA chains (>16C’s)

•longer fatty acids are produced with special enzymes that add two-carbon acetyl units to the carboxyl end of the fatty acid chain.

how does insulin regulate fatty acid synthesis

-when blood glucose is high, it is released and moves the glucose into the cells to stimulate glycolysis and oxidation of pyruvate (into acetyl CoA)

-the buildup of acetyl CoA initiates fatty acid synthesis (making fat)

in these circumstances, what happens to the transport of acyl group into the matrix of mitochondria

they are blocked to prevent their oxidation (which leads to energy production) so they can undergo fatty acid synthesis in adipose tissue

beta oxidation vs Fatty acid synthesis

NOW WE START PROTEINS

when carbs and lipids are not available,

amino acids are degraded to substrates that enter energy-producing pathways

where does protein digestion begin

in the stomach

HCL in the stomach (the acidity) does what

denatures the proteins

pepsin

hydrolyses the proteins into polypeptide chains