Name 3 fatty fuels in the body
lipids transported via lipoproteins
NEFA bound to plasma albumin
What major muscle utilizes fatty acids as a major source of energy?
cardiac muscle tissue
What proteins are involved in transport of endogenous TAG from liver to adipose tissue?
What structure transports exogenous TAG from the intestines to adipose tissue?
What type of cells produce lipoprotein lipases?
What hormone inactivates hormone-sensitive lipase? What is the mechanism behind the inactivation?
Name 2 hormones that activate hormone-sensitive lipase. What is the mechanism behind this activation?
epinephrine & norepinephrine
What hormone activates lipoprotein lipase? To what end?
lipoprotein lipase hydrolyzes TAG-rich blood lipoprotein particles in the blood; thus favoring lipogenesis
Why do adipocytes depend on glucose for glycerol 3-phosphate (name the missing enzyme)?
adipocyes lack glycerol kinase
What type of bond is formed in the activation step of fatty acid oxidation?
What 2 groups form the thioester bond in the activation step that precedes fatty acid oxidation?
COOH of NEFA
thiol group of coenzyme A
What enzyme is involved in the initiation step of fatty acid oxidation?
acyl-CoA synthetase (thiokinase)
What type of mechanism is involved in the movement of acyl-carnitine esters into the mitochondrial matrix?
acyl-carnitine in:carnitine out
What are the 2 primary sites of carnitine synthesis?
Name the 3 enzymes involved in the carnitine shuttle mechanism
carnitine palmitoyl transferase 1
carnitine palmitoyl transferase 2
Name 3 symptoms of carnitine deficiency
general muscle weakness
Name 2 symptoms of carnitine deficiency in regards to blood sugar and ketone bodies.
Name 5 causes of carnitine deficiency
failure to synthesize carnitine
failure in cellular uptake of carnitine
CPT-2 deficiency (particularly in cardiac & muscle)
carnitine translocase deficiency
Which carnitine deficiency primary affects the liver?
Name the disease: reduced fatty acid oxidation in skeletal and cardiac muscle, cardiomyopathy, muscle pain, cramps following prolonged exercise, myoglobinuria
What type of diet is required for people suffering from CPT-2 deficiency?
high carbohydrate/low fat diet
Name the disease: muscle weakness, hypoglycemia, hyperammonemia, cardiomyopathy
translocase deficiency (carnitine deficiency)
Which disease is characterized by defective carnitine transport into muscle, kidney & heart tissue from plasma?
primary carnitine deficiency
Name the disease: defects in B-oxidation pathway leads to accumulation of acyl-carnitines which are excreted by the kidneys, depleting the carnitine pool
secondary carnitine deficiency
List the intermediates and enzymes of the beta-oxidation pathway
fatty acyl CoA + FAD (acyl CoA dehydrogenase)
delta2-trans-enoyl CoA + H2O (enoyl-CoA hydratase)
Beta-hydroxyacyl CoA + NAD+ (beta-hydroxyacyl CoA dehydrogenase)
B-ketoacyl CoA (acyl CoA acyltransferase (thiolase)) + CoA
fatty acyl CoA & acetyl-CoA
Given palmitic acid, how many acetyl-CoAs, FADH2, and NADH+H+ molecules are formed at the completion of one cycle of beta-oxidation?
7 NADH + H+
How much ATP is yielded from each acetyl CoA molecule?
What is the function of carnitine palmitoyl transferase I?
Where is CPT1 located?
outer membrane of mitochondria
Where is CPT2 found?
inner membrane of mitochondria
What is the function of CPT2?
CPT2 converts acylcarnitine back to acyl-CoA once it is inside the mitochondrial matrix.
At what age can carnitine deficiency present (general range)?
neonates to teenagers
Why does hypoglycemia result from CPT-1 deficiency?
loss of fatty oxidation leads to loss of ATP for gluconeogenesis
Which carnitine deficiency leads to hypoketosis?
Which carnitine deficiency is lethal?
Which carnitine deficiency is characterized by brown urine?
How many molecules are carried by an albumin protein?
8 molecules of free fatty acid
What type of cells can use fatty acids and glucose for energy?
Name 6 extracellular lipases
hepatic TAG lipase
endothelial lipase (lung, kidney & liver)
bile salt-stimulated lipase (human breast milk)
Name 2 intracellular lipases
hepatic intracellular lipase
Where is bile salt-stimulated lipase found?
What 2 molecules are formed within adipocytes?
How is TAG transported from the liver to the adipose tissue?
Through which transporter does glucose enter white adipose tissue?
Do adipocytes have receptors for glucagon?
Name 4 conditions that stimulate TAG mobilization
decreased environmental temperature
Describe how epinephrine and insulin affect TAG mobilization.
Increased epinephrine and decreased insulin will increase TAG mobilization.
Where is TAG hydrolyzed by lipoprotein lipase?
After hydrolysis of TAG, glycerol is delivered by the blood to the _____. It is phosphorylated by the enzyme _____ and then oxidized to _____, an intermediate of _____. Adipocytes cannot perform these actions because they lack the enzyme _____.
What molecule provides the backbone (glycerol) to the TAG molecule in the adipocyte?
What are the 2 fates of intracellular NEFAs?
complex lipid synthesis
oxidation producing energy
What are the 3 types of long chain fatty acid oxidative pathways?
Where does beta-oxidation occur (2)?
Where does alpha-oxidation occur?
Where does omega-oxidation occur?
Where does the activation step of fatty acid oxidation occur?
Name 3 therapeutic approaches towards carnitine deficiency
diet low in LCFAs
avoid fasting (requires acyl-oxidation)
diet supplemented MCFAs that do not rely on carnitine transport systems
Why are patients with carnitine deficiency disorders given MCFAs?
MCFAs can enter the mitochondria without use of carnitine shuttles
List the 4 steps of the beta-oxidation cycle
oxdation to produce FADH2
oxidation that produces NADH + H+
thiolysis that releases acetyl CoA
How can primary carnitine deficiency be treated?
dietary carnitine therapy
Where are 2 ATPs lost during oxidation of fatty acids?
activation step converts ATP to AMP + 2Pi
What 2 fatty acids are found in patients during the acute phase of Jamaican vomiting sickness?