62 terms

Intro to lipid metabolism (43)

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Name 3 fatty fuels in the body
lipids transported via lipoproteins

NEFA bound to plasma albumin

ketone bodies
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?
VLDLs
What structure transports exogenous TAG from the intestines to adipose tissue?
chylomicrons
What type of cells produce lipoprotein lipases?
adipocytes
What hormone inactivates hormone-sensitive lipase? What is the mechanism behind the inactivation?
insulin

dephosphorylates HSL
Name 2 hormones that activate hormone-sensitive lipase. What is the mechanism behind this activation?
epinephrine & norepinephrine

phosphorylates HSL
What hormone activates lipoprotein lipase? To what end?
insulin

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?
thioester bond
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?
antiport

acyl-carnitine in:carnitine out
What are the 2 primary sites of carnitine synthesis?
liver

kidneys
Name the 3 enzymes involved in the carnitine shuttle mechanism
carnitine palmitoyl transferase 1

carnitine palmitoyl transferase 2

membrane-bound translocase
Name 3 symptoms of carnitine deficiency
hepatomegaly

cardiomyopathy

general muscle weakness
Name 2 symptoms of carnitine deficiency in regards to blood sugar and ketone bodies.
hypoketotic

hypoglycemic
Name 5 causes of carnitine deficiency
failure to synthesize carnitine

failure in cellular uptake of carnitine

CPT-1 deficiency

CPT-2 deficiency (particularly in cardiac & muscle)

carnitine translocase deficiency
Which carnitine deficiency primary affects the liver?
CPT-1 deficiency
Name the disease: reduced fatty acid oxidation in skeletal and cardiac muscle, cardiomyopathy, muscle pain, cramps following prolonged exercise, myoglobinuria
CPT-2 deficiency
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?
8 acetyl-CoAs

7 FADH2

7 NADH + H+
How much ATP is yielded from each acetyl CoA molecule?
12 ATP
What is the function of carnitine palmitoyl transferase I?
acyl-CoA

acyl-carnitine
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?
CPT-1 deficiency
Which carnitine deficiency is lethal?
CPT-1 deficiency
Which carnitine deficiency is characterized by brown urine?
CPT-2

*myoglobinuria
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?
myocytes
Name 6 extracellular lipases
gastric lipase

pancreatic lipase

lipoprotein lipase

hepatic TAG lipase

endothelial lipase (lung, kidney & liver)

bile salt-stimulated lipase (human breast milk)
Name 2 intracellular lipases
hormone-sensitive lipase

hepatic intracellular lipase
Where is bile salt-stimulated lipase found?
mammary glands
What 2 molecules are formed within adipocytes?
TAG

cholesterol esters
How is TAG transported from the liver to the adipose tissue?
VLDL
Through which transporter does glucose enter white adipose tissue?
GLUT4
Do adipocytes have receptors for glucagon?
NO!
Name 4 conditions that stimulate TAG mobilization
fasting

exercise

diabetes

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?
blood capillaries
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 _____.
liver

glycerol kinase

dihydroxyacetone phosphate

glycolysis

glycerol kinase.
What molecule provides the backbone (glycerol) to the TAG molecule in the adipocyte?
glucose
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?
beta-oxidation

alpha-oxidation

omega-oxidation
Where does beta-oxidation occur (2)?
mitochondria

peroxisomes
Where does alpha-oxidation occur?
peroxisomes
Where does omega-oxidation occur?
smooth ER
Where does the activation step of fatty acid oxidation occur?
mitochondrial matrix
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

hydration

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?
butyric acid

hexanoic acid