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76 Cards in this Set

  • Front
  • Back
How is glycerol 3P made in the liver?
glycerol kinase in the liver converts glycerol to glycerol 3P
How is glycerol 3P made in adipose tissue?
from glucose via DHAP
Does adipose tissue have glycerol 3P?
No, it utilized DHAP to make Glycerol 3P
Where is the majority of TAGs formed?
in the liver
How is phosphatidic acid formed?
Glycerol 3P reacts with fatty acyl CoA
What is the product of dephosphorylation of phosphatidic acid?
diacylglycerol
How are TAGs formed?
1. Glycerol 3 P reacts with a fatty acyl CoA to form phosphatidic acid + CoA
2. Phosphatidic acid is dephosphorylated to form a diacylglycerol
3. diacylglycerol reacts with a fatty acyl CoA to form a triacylglycerol (TAG) + CoA
Where are TAGs formed in the cell?
Smooth ER of the liver
What makes up VLDL?
TAGs packaged with cholesterol, phospholipids and proteins
What is required for VLDL and chylomicron assembly?
MTP: Microsomal triglyceride transfer protein
What happens if a patient lacks MTP?
Problems packing fat and transporting it
What is the major protein in VLDLs?
apoB-100
Where are VLDLs processed?
In the golgi complex
What is the function of lipoprotein lipase (LPL)?
To cleave the TAGs in the VLDL and chylomicrons into fatty acids and glycerol
When is lipoprotein lipase secreted? From where?
LPL is secreted when insulin/glucagon ratio is elevated (in the fed state) by adipose cells
What enzyme are adipose cells lacking in G3P formation?
Glycerol kinase
What happens to the glycerol produced by LPL once in adipose cells?
It is taken up in the liver and reused
How do LDLs affect the heart?
Strong correlation between LDL and heart disease
How do HDL levels affect the heart?
Strong correlation between HDL levels and decreased risk of heart disease
What is the function of HDLs?
Remove lipids from plaques and transports them back to the liver for processing
What causes cAMP levels to rise in adipose tissues?
Decrease in insulin and rise in glucagon
What do increasing cAMP levels stimulate?
liposlysis
How is protein kinase A involved in lipolysis?
Protein kinase A phosphorylates hormone-sensitive lipase to activate it, which then cleaves fatty acid from TAGs
What happens once FA have been cleaved from TAGs by hormone-sensitive lipase?
Other lipases finish the process and liberate fatty acids and glycerols into the blood
What does hormone-sensitive lipase act on?
Triacylglycerols, the remaining diacyglycerol is acted on by other lipases
What is the pKa of a FA carboxyl group?
4.8
How do double bonds influence the melting point of fatty acids?
They decrease the melting points
What fatty acids are nutritionally essential?
1. Linoleic acid
2. alpha-linolenic acid
What is linoleic acid?
18:2 (9,12)
What is alpha-linolenic acid?
18:3 (9,12,15)
Which is an omega-3 fatty acid, linolenic or linoleic?
Linolenic

Linoleic is omega-6
What are examples of the most common dietary saturated FA's?
1. Myristic acid (14:0)
2. Palmitic acid (16:0)
How do saturated fats influence cholesterol?
Saturated fats elevate cholesterol levels
What are examples of dietary monounsaturated FA's?
Olive oil, it is high in oleic acid (18:1, cis 9)
How do monounsaturated FA's influence cholesterol?
Lowers both chol and LDL with NO effect on HDL
What is the primary dietary polyunsaturated fat in the human diet?
Linoleic acid (18:2, cis 9,12)
What is the primary omega-6 (N-6) polyunsaturated FA in our diet?
Linoleic acid (18:2, cis 9,12)
How do omega-6 FAs influence cholesterol?
Lowers both LDL and HDL
What is linoleic acid (omega-6 PUFA) required for?
Synthesis of eisoanoids, membrane fluidity
What is the primary omega-3 PUFA?
alpha-linolenic acid (18:3, cis 9,12,15)
How does alpha linolenic acid influence cholesterol?
It has little effect of LDL or HDL
omega-3 vs omega-6 fatty acids:
Omega-6 fats compete with beneficial omega-3 fats for specific enzymes that metabolize PUFAs
Why are omega-3 FAs beneficial for?
little effect on cholesterol, primary good for cell signalling, blood pressure, other systems...
What are the effects of omega-3 FAs?
1. Reduce BP
2. Treat infection
3. Treat psoriasis
4. Anti-inflammatory
5. Antithrombotic
6. Anti-arrhythmia
How do trans fatty acids influence cholesterol? CV disease?
Raise LDL levels and promote artherosclerosis

Thought to promote heart disease
What is an example of a trans fat?
Elaidic acid
How many types of aceyl CoA dehydrogenase are there?
3
What do aceyl CoA dehydrogenase do?
Act of fatty acid chain to introduce the double bond between the alpha and beta carbons to make enoyl CoA
What cofactor is required for aceyl CoA dehydrogenase?
FAD+
Where does oxidation of fatty acids occur in the cell?
Mitochondria
What is AMP-activated protein kinase?
AMP-activated protein kinase is activated by AMP, and phosphorylates Acetyl CoA carboxylase to make it inactive, therefore decreasing fatty acid synthesis

*Low energy (AMP) would not want to store and synthesize fats
How does palmitoyl-CoA regulate Acetyl-CoA carboxylase?
palmitoyl CoA, the primary product of FA synthase, would inhibit acetyl CoA carboxylase through feedback inhibition bc no more FA would need to be made
How does protein kinase A regulate acetyle coA carboxylase?
Protein kinase a phosphorylates acteyl coa carboxylase making the enzyme inactive
How does glucagon regulate acetyl CoA carboxylase?
Glucagon turns on cAMP, which turns on protein kinase A, protein kinase A phosphorylates acetyl CoA carboxylase and inactivates it, halting FA synthesis
How does epinepherine regulate FA synthesis?
epinepherine increases cAMP, which activates protein kinase A, which turns off acetyl coA carboxylase, stopping FA synthesis
How does insulin regulate acetyl coA carboxylase?
Insulin turns off AMP-activated protein kinase and decreases cAMP, which in turn shuts off protein kinase A. This would prevent both means of phosphorylating acetyl CoA carboxylase, keeping it active and increasing FA synthesis

This makes sense bc we want to store fats during the fed state
How does citrate regulate acetyl coA carboxylase?
Allosteric activator (may increase polymerization of acetyl CoA carboxylase, increasing the enzymes activity
What is hypoglycin A?
An amino acid that is found in unripe akee fruit
What does hypoglycin A do?
Inhibits acyl CoA dehydrogenase
What are the clinical effects of hypoglycin A?
Fasting hypoglycemia (especially severe in people with low levels of acyl CoA dehydrogenase)

Symptoms: vomiting, convulsions, coma
How does hypoglycin A cause hypoglycemia?
Hypoglycin A inhibits Acyl CoA dehydrogenases. Acyl CoA dehydrogenases are responsible for the first step of beta oxidation. If this is inhibited, fats cannot be oxidized in fasting state.
Where are the greatest effects of beta-oxidation deficiencies seen?
Tissues that rely of beta oxidation for energy:
1. Skeletal muscles
2. Liver (during fasting)
What is the result of a carnitine deficiency?
Carnitine is used to transport fatty acids into the mitochondria for beta oxidation. If the fatty acids are not able to get into the inner mitochondrial membrane, beta oxidation cannot occur. This would compromise ketogenesis and ATP production during fasting

Result: hypoketotic (bc no generation of AcCoA for ketogeneiss) hypoglycemia (bc no ATP for gluconeogenesis)
What is the most common beta-oxidation defect?
Medium chain acyl CoA dehydrogenase deficiency
What are medium chain FAs?
C5-12
How does medium chain acyl CoA dehydrogenase deficiency present?
Often infant or children come in (usually when sick bc not eating enough) with hypoglycemia during fasting.
* May be linked to SIDS bc many infants die during their first hypoglycemic attack bc goes undiagnosed
Where is medium chain acyl CoA dehydrogenase deficiency most common? Why?
NW Europe bc a single mutation is responsible for 90% of cases
What is Refsum Disease?
Recessively inherited defect of peroxisomal alpha-oxidation
What does Refsum disease cause?
accumulation of phytanic acid
What is phytanic acid?
Branched chain FA derived from phytol
What is phytol?
constituent of chlorophyll that accumulates in the fat of ruminants
What are the symptoms of Refsum disease? Treatment
muscle wasting, neuropathy, weakness, degeneration of the retina, cerebellar ataxia

Treatment: catch early bc neurological problems are irreversible, restrict dietary green veggies and ruminant milk and meat
What do LDLs do?
Deliver cholesterol to the tissues
What do VLDLs do?
carry triglycerides to the peripheral tisuses
What is the pathophysiology of Refsum disease?
Propinoyl CoA is made instead of AcCoA, which requires more enzymes
What is AI lipoprotein thought to do?
reverse cholesterol and plaque