6- Lipid Mobilization and Catabolism Flashcards
How is hormone sensitive lipase regulated?
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.
Path of triglycerides
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
Why is B oxidation important?
Because gluconeogenesis requires energy from the B ox process. (Gluconeogenesis happens in the liver).
B ox will go first and then gluconeogenesis, ( during starvation)
What is a ketone body consist of?
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
Why is Acetyl CoA important in gluconeogenesis?
It is the key activator of one of the key enzymes in gluconeogenesis, pyruvate carboxylase.
How are different sized chains transported for B oxidation?
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
Carnitine shuttle
transport long (14-20 C) chain fatty acids to mitochondria
B oxidation
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
Activation and transport of FA
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
B oxidation
FACoA > produces FADH2»_space; produces NADH»_space;Acetyl CoA
Fatty acylCoA dehydrogenase:
FA-CoA to produce FADH2
Carnitine deficiency
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
Other B oxidation diseases
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
What are the products of B oxidation that will be used to make ATP?
Acetyl CoA
FADH2
NADH
Water is also produced after ATP production
a oxidation
removal of 1C from carboxyl end.
Has been detected in brain tissue.
Does not generate CoA or high-energy phosphates.
w oxidation
minor pathway in ER.
produces dicarboxylic acid which undergoes b ox and secreted in urine
Ketogenesis
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
Ketone body metabolism
AcetylCoA is produced by b oxidation
AcetylCoA > HMG CoA > acetoacetate > acetoacetate/acetone/3-hydroxybutyrate
HMG CoA synthase
acetyl CoA > HMGcoA
HMGCoA lyase:
HMGCoA > acetoacetate
Why does AcCoA go to ketogenesis instead of TCA?
In glucagon world, gluconeogenesis is happening so no OAA to combine with Acetyl CoA. AcCoA builds up and goes to ketogenesis
Difference between HMG CoA in ketogenesis and cholesterol sytnthesis?
HMGCoA keto- in mito of liver
HMGCoA cholesterol- in every cell of body except RBC
When does liver make Kbs?
90 min after high carb meal
Muscles use it in prolonged starvation
Ketosis
Increase in Kbs in the blood cause ketoacidosis because actoaceatic and 3 hydroxybutyrate are acidic.
ketonuria
increase KB in urine is excreted.
Oscmotic so it draws water and dehydrates. drink lots during starvation
Ketogenic diet
used to treat difficult to control epilepsy in children.
high-fat, adequate protein, low carb diet
forces body to use fat instead of carbs.
Why can’t liver use ketone bodies?
THiophorase is absent in liver
