6- Lipid Mobilization and Catabolism

Question 1

How is hormone sensitive lipase regulated?

Answer 1

HSL activity increases when insulin is low, and epinephrine and cortisol are high. Active when phosphorylated.

HSL is in adipose tissue. Breaks down TGL to Glycerol and fatty acids.

Question 2

Path of triglycerides

Answer 2

TGL + HSL > FA + Glycerol

Glycerol (water soluble) > blood > Liver > gluconeogenesis > glucose

FA > FA Albumin(can go to any cell) > Liver > B oxidation > acetyl coA > TCA or to Ketogenesis

• any cell that has mitochondria can do B oxidation
• Ketone bodies are packages of acetyl CoA

Question 3

Why is B oxidation important?

Answer 3

Because gluconeogenesis requires energy from the B ox process. (Gluconeogenesis happens in the liver).

B ox will go first and then gluconeogenesis, ( during starvation)

Question 4

What is a ketone body consist of?

Answer 4

4 acetyl CoA- formed in the liver by B ox, then can go to TCA or Ketogenesis (makes ketone bodies in liver than gets dumped in the blood)

Used by cardiac muscles brain and sometime kidney in times of

Question 5

Why is Acetyl CoA important in gluconeogenesis?

Answer 5

It is the key activator of one of the key enzymes in gluconeogenesis, pyruvate carboxylase.

Question 6

How are different sized chains transported for B oxidation?

Answer 6

Short (2or 4 C)and medium (6-12C) chains diffuse freely into mitochondria to be oxidized.

Long chains (14-20C) are transported via Carnitine shuttle

Very long (>20) chains enter peroxisomes for B ox

Question 7

Carnitine shuttle

Answer 7

transport long (14-20 C) chain fatty acids to mitochondria

Question 8

B oxidation

Answer 8

Carbons are picked off by 2 C units, released as acetyl CoA. Removing electrons from carbon chain and capturing it to be used later on.

Starts with B carbon to carboxyl carbon. C3

Must first be activated by formation of acyl CoA

Question 9

Activation and transport of FA

Answer 9

Starts outside the membrane

acyl-CoA synthetase:
FA + CoA + ATP > fatty acylCoA + AMP + PPi

fatty acylCoA moved into inner membrane space

Carnitine acyltransferase 1:
FACoA > FA carnitine

Carnitine transporter:
Moves FA carnation into mitochondrial matrix.

Carnitine acyltransferase 2:
FA carnitine > FA CoA

Question 10

B oxidation

Answer 10

FACoA > produces FADH2&raquo_space; produces NADH&raquo_space;Acetyl CoA

Fatty acylCoA dehydrogenase:
FA-CoA to produce FADH2

Question 11

Carnitine deficiency

Answer 11

Can occur in newborn or pre-term infants due to inadequate biosynthesis or renal leakage.

Leads to impaired carnitine shuttle activity

Long Chain FA will not be metabolised and will accumulate in tissues. Waisting of acyl carnitine in urine produces:

Cardiomyopathy, skeletal muscle myopathy, encephalopathy, and impaired liver function. Because in starvation there is not enough ATP for them to run.

Due to inherited CTP-I or CPT II diesease (recessive). Impaired carnitine synthesis due to liver disease

Question 12

Other B oxidation diseases

Answer 12

CPT-I: deficiency affects only liver, hypoglycemia, inability to use LCFAs as fuel by liver

CPT-II: affects skeletal muscle, muscle weakness upon exercise, hyperammonemia, death
— rare disease

Both treated by avoiding fasting, dietary restriction of LCFAs, carnitine supplement

Question 13

What are the products of B oxidation that will be used to make ATP?

Answer 13

Acetyl CoA
FADH2
NADH

Water is also produced after ATP production

Question 14

a oxidation

Answer 14

removal of 1C from carboxyl end.

Has been detected in brain tissue.

Does not generate CoA or high-energy phosphates.

Question 15

w oxidation

Answer 15

minor pathway in ER.

produces dicarboxylic acid which undergoes b ox and secreted in urine

Question 16

Ketogenesis

Answer 16

Ketone body formation.

Occurs in mitochondria of liver when too much acetyl CoA accumulates in fasting state.

occurs when high rate of FA oxidation in liver

Acetone (expired to lungs- fruity smell), acetoacetate, and a-3-hydroxybutylate
— these three are known as the ketone bodies

Question 17

Ketone body metabolism

Answer 17

AcetylCoA is produced by b oxidation

AcetylCoA > HMG CoA > acetoacetate > acetoacetate/acetone/3-hydroxybutyrate

HMG CoA synthase
acetyl CoA > HMGcoA

HMGCoA lyase:
HMGCoA > acetoacetate

Question 18

Why does AcCoA go to ketogenesis instead of TCA?

Answer 18

In glucagon world, gluconeogenesis is happening so no OAA to combine with Acetyl CoA. AcCoA builds up and goes to ketogenesis

Question 19

Difference between HMG CoA in ketogenesis and cholesterol sytnthesis?

Answer 19

HMGCoA keto- in mito of liver

HMGCoA cholesterol- in every cell of body except RBC

Question 20

When does liver make Kbs?

Answer 20

90 min after high carb meal

Muscles use it in prolonged starvation

Question 21

Ketosis

Answer 21

Increase in Kbs in the blood cause ketoacidosis because actoaceatic and 3 hydroxybutyrate are acidic.

Question 22

ketonuria

Answer 22

increase KB in urine is excreted.

Oscmotic so it draws water and dehydrates. drink lots during starvation

Question 23

Ketogenic diet

Answer 23

used to treat difficult to control epilepsy in children.

high-fat, adequate protein, low carb diet

forces body to use fat instead of carbs.

Question 24

Why can’t liver use ketone bodies?

Answer 24

THiophorase is absent in liver

Question 25

When will you find acetone in breath?

Answer 25

Diabetic ketoacisosis

prolonged starvation

Acetone goes to lungs.

Question 26

Diabetic ketoacidosis

Answer 26

predominantely in type 1 diabetics, can occur in type II

DKA happens from shortage of insulin, in response body switches to using fatty acids –> produce acidic ketone bodies –>

No insulin, no LPL activity to store fatty acids.

Question 27

Brain fuel use

Answer 27

12 hours: fuel from glucose and glycogen breakdown (liver)
after 12: muscle protein breakdown

C for glu comes from lactate, pyr., glycerol mostly from aa for about a week of starvation

glucose derived from gluconeogenesis to ketones derived from FAs after 1 week.

C from Kbs and brain slows down. This c from adipose tissue, from FA