Fatty Acid Metabolism

Question 1

Why is fat more energetic per gram than glycogen?

Answer 1

It is more reduced

It does not bind water

Question 2

What are the major fatty acid components of the diet?

Answer 2

Palmitate
Stearol
Oleate
Linoleate

Question 3

How are fatty acids transported in the blood?

Answer 3

Primarily bound to serum albumin

Free fatty acids are toxic if they accumulate in too great of quantities

Question 4

Describe the stratification of fatty acids

Answer 4

Very Long chain are greater than 20
Long chain are 12 to 20
Medium chain are 6-12
Short chain are less than 6
Long chain are broken down by beta oxidation
Very long chain require peroxisomal breakdown first

Question 5

Describe the activation of fatty acyl groups to Acyl CoA

Answer 5

Fatty acid attacks the primary phosphate group of ATP causing PPi to leave. Hydrolysis of PPI helps to provide energy for the bonding of CoA to the acyl group and the lysis of the bond between the acyl group and AMP
Whole thing produces AMP, 2Pi, and Acyl CoA

Question 6

What are the possible fates of fatty acyl CoA

Answer 6

B-oxidation, Ketogenesis, Triacylglycerols (storage), Membrane lipids

Question 7

Describe transport of acyl CoA into the inner mitochondrial matrix

Answer 7

Acyl Coa is transported into the intermembrane space where it is converted to acyl-carnitine by CPT I. It is transported into the matrix by Carnitine acyl carnitine translocase in exchange for carnitine from the matrix. It is then converted back to Acyl-CoA by CPTII and undergoes B oxidation

Question 8

Describe B oxidation

Answer 8

Acyl coa dehydrogenase converts acyl coa to trans fatty enoyl coa with a double bond between carbon 2 and 3 creating FADH2. enoyl coa hydratase converts trans 2 fatty enoyl coa to B hydroxy acyl coa. b hydroxyl acyl coa dehydrogenase creates B keto acyl coa and NADH. B keto thiolase utilizes thiolytic cleavage at the B carbon and shorted the fatty acid by two.

Question 9

Describe B oxidation of unsaturated fatty acids

Answer 9

B oxidation occurs normally until it encounters a 3,4 6,7 double bond. Enoyl coA isomerase converts the 3,4 double bond to a 2,3 double bond. One beta oxidation occurs then 2,4 dienoyl coa reductase uses NADPH to convert the two double bonds to a single 3,4 double bond. Enoyl coa reductase does it’s job again and B oxidation continues.

Question 10

Why is energy yield less from unsaturated FAs

Answer 10

Less FADH2 is produced (no need for initial reduction)

NADPH expended which costs the cell 2.5 atp

Question 11

Describe B oxidation of odd chain length fatty acids

Answer 11

B oxidation continues normally until it creates proprionyl CoA. Proprional CoA carboxylase adds a carbon to the three carbon structure using bicarbonate and ATP. Methylmalonyl CoA epimerase moves the CoA to the second carbon. Methylmalonyl CoA mutase moves it to the third carbon to create succinyl CoA.

Question 12

What are the fates of succinyl CoA

Answer 12

Replenish the TCA cycle
Provide carbon for gluconeogenesis
Oxidation to Co2 and H20 for energy

Question 13

What happens to Medium Chain Length Fatty Acids

Answer 13

Monocarboxylate transporter moves them directly into the matrix where they are converted to acyl-CoA by MCL-AcCoa Synthase.
They undergo beta oxidation by Medium chain length isozymes.
Can also be conjugated to glycine or carnitine for excretion in urine

Question 14

How does AMP stimulate fatty acid oxidation?

Answer 14

Activation of AMP-PK inhibits Acetyl CoA Carboxylase which causes a decrease in Malonyl CoA removing inhibition of CPT1 and allowing conversion of Fatty Acyl CoA into Fatty Acyl Carnitine for uptake into the matrix.

Question 15

Describe peroxisomal FA Oxidatoin

Answer 15

VLCFA are brought into the peroxisome where They are oxidized by FAD oxidase in a step that does not produce energy but does produce peroxide. They are then broken down to MCFA and SCFA and sent to the mitochondrial matrix for B oxidation

Question 16

What is Zellweger syndrome?

Answer 16

Peroxisomal storage disorder resulting from a defect in breakdown of LCFA
Mainly effects the liver and brain
Note elevated plasma LCFAs

Question 17

What are Mixed Function Oxidase reactions?

Answer 17

A hydroxylase can insert oxygen on essentially any carbon it wants. Multiple insertions at the same carbon lead to decarboxylations or chain length cleavage.
A hydroxylase does this to LCBFAs in order to remove the branches allowing it to proceed with normal B oxidation

Question 18

What is Refsum Disease

Answer 18

A-hydroxylase deficiency leading to an inability to break down phytanic acid derived from plant material. Accumulation leads to symptoms that are mainly neurologic.
Dietary restriction is the treatment

Question 19

What is omega oxidation and where does it take place?

Answer 19

Takes place in Smooth ER
Oxidation of the omega carbon by a MFO followed by action of dehydrogenation creates a n oxidation site allowing for B oxidation from the W carbon. This is used for metabolism of xenobiotics.
Also used when normal B oxidation is defective
Creates C6-8 dicarboxilic acids, often indicate a disorder of FA oxidation

Question 20

What is normal blood glucose?

Answer 20

Anywhere between 8 and 3 mM

5mM = 90mg/dL

Question 21

Why is glucose important for the brain?

Answer 21

The brain has a massive appetite
Cannot use fatty acids as fuel due to blood brain barrier
Can use ketone bodies during starvation

Question 22

Describe the absorptive phase of the feast starve cycle

Answer 22

Exogenous origin of blood glucose
All tissues use glucose
Major brain fuel is glucose
Lasts about 4-8 hours

Question 23

Describe the Postabsorptive phase

Answer 23

Glycogen and hepatic gluconeogenesis source of blood glucose
All tissues except liver use glucose
Brain uses glucose
Lasts until 16 hours

Question 24

Describe early starvation

Answer 24

Hepatic gluconeogenesis and glycogen create blood glucose
All tissues except liver use glucose for fuel
Brain Uses Glucose
Lasts until about 2 days

Question 25

Intermediate Starvation

Answer 25

Gluconeogenesis from liver and kidney make blood glucose
Brain, Rbcs, kidney medulla, some muscle use glucose
Major source of brain food is ketone bodies
Lasts until 24 days

Question 26

Prolonged Starvation

Answer 26

Gluconeogenesis from kidney and liver make glucose
RBCs and kidney medulla use glucose
Brain primarily used Ketone Bodies, some glucose

Question 27

What are hormonal stimuli for use of Ketone Bodies

Answer 27

Increased epinephrine
Increased Glucagon
Decreased insulin

Question 28

What tissues don’t use ketone bodies

Answer 28

Liver (lacks enzyme for their use)

RBCs (lacks enzyme for their use)

Question 29

What happens when the brain upregulates ketone body transporters

Answer 29

Gluconeogenesis does not need to be as extensive which spares muscle because it does not have to break down proteins to alanine at as high of a rate
This also leads to less production of urea because breakdown of proteins is less so nitrogenous waste is less

Question 30

Where and how are ketone bodies synthesized?

Answer 30

Ketone bodies are synthesized in the mitochondrial matrix of the liver
They are created from two Acetyl Coa molecules and create acetoacetate which can be reduced to B hydroxybutyrate or spontaneously decarboxylate to form acetone which gives a “fruity” scent to the breath

Question 31

How to peripheral tissues use ketone bodies?

Answer 31

Use succinyl-coa;acetoacetate coa transferase with succinyl coa as a cofactor to create acetoacyl coa and succinate. Acetoacetyl coa undergoes thiolytic cleavage to become two molecules of acetyl coa which can undergo oxidative phosphorylation

Question 32

How much ATP is created by KBs

Answer 32

21.5 ATP, 10 each from the Acetyl CoA and 1.5 from FADH2

Question 33

Why is acyl uptake continued during the fasting state?

Answer 33

No acetyl-coa carboxylase is synthesized therefore no malonyl-coa is present to inhibit CPT1 which remains constitutively active

Question 34

What are some facts about glycogen

Answer 34

20,000-30,000 Glc Residues/Molecule
7-10% at non-reducing termini
60% in outer branches
30% in inner branches
Clusters of 300A b particles form A particles

Question 35

What is the typical daily calorie expenditure at rest?

Answer 35

2500 Cal

Basal 1800 Cal

Question 36

What is the typical glycogen content of the liver?

Answer 36

742 kcal at Max
300 kcal after a meal
After short fast 200 kcal
After 24-36 hour fast 15 kcal
Liver stores are almost gone after 24 hours

Question 37

Glycogen content of muscle

Answer 37

Overnight fast 500 kcal
After meal 600-700 kcal
Carboload 1000 kcal
After prolonged fast 250 kcal
Never depletes because it is required to function

Question 38

Why store glucose as a polymer

Answer 38

More water soluble so less likelihood of precipitation leading to disease
Allows for more terminal site for attack of enzymes promoting rapid breakdown

Question 39

What organ is responsible for maintaining average blood glucose? What is average blood glucose?

Answer 39

The liver either removes or adds glucose

Normally there is around 20 kcals of glucose in blood

Question 40

Describe glycogen catabolism

Answer 40

Glycogen is degraded by glycogen phosphorylase which creates Glucose-1-P. When within 4 residues of a branch then an unbranching enzyme removes three residues and puts them on the adjacent branch. The lasetresidue is spontaneously lost as glucose. Phosphoglucomutase conversts G1P into G6P and G6P phosphotase creates glucose which can be exported into the blood (liver only)

Question 41

Why do you get one extra ATP per G1P?

Answer 41

It is already phosphorylated so there is no need for “priming” of the pump.

Question 42

Describe glycogen synthesis

Answer 42

Glucose 6 P is converted to Glucose 1 P by phosphoglucomutase. UDP glucose pyrophosphorylase uses UTP to create UTP glucose. UTP glucose can then be used in other pathways or can undergo action by Glycogen synthase to become glycogen

Question 43

How many ATP are required to store glucose as glycogen

Answer 43

2

Question 44

Why is glucose not stored as fat?

Answer 44

Storing glucose as glycogen results in a 6% loss of energy while storing it as fat results in a 25% loss of energy

Question 45

What is the action of glycogen synthase and glycogen phosphorylase when they have been phosphorylated by PKA

Answer 45

Glycogen phosphorylase is active

Glycogen synthase is inactive

Question 46

Describe regulation of glycogen when glucagon and epinephrine bind to their receptors

Answer 46

G protein activates adenylate cyclase.
Cyclic AMP activates PKA
PKA phosphorylates glycogen synthase inactivating it
PKA phosphorylates phosphorylase kinase which phosphorylates glycogen phosphatase activating it.