Lecture 4: Lipid Metabolism Flashcards
Where is fatty acid metabolized?
Mitochondria
Once taken up by the cell, what are fatty acids used for?
1) Precursor for synthesis of other compounds
2) Energy production
3) Substrate for ketone body synthesis
What is the major form of energy storage?
Fat
What is the structure of acetyl CoA?
Acetyl group and Coenzyme A
What does Coenzyme A consist of?
- Beta-mercaptoethylamine
- Pantothenic acid (not synthesized in man = an essential nutrient)
- Phosphate
- 3’, 5’-adenosine diphosphate
What is the structure of a fatty acid?
1) A long hydrocarbon chain
2) A carboxylic acid group
What is the length of a hydrocarbon chain in a fatty acid? What is the most common length?
The chain length ranges from 4 to 30 carbons; 12-24 is the most common.
What is the shape of a fatty acid?
linear
Carbons in a fatty acid are always _____.
even
How many double bonds does a saturated fatty acid have?
0 double bonds
What are examples of a saturated fatty acid?
stearic acid and palmitic acid
How many double bonds does a monosaturated fatty acid have?
1 double bond
What is an example of a monosaturated fatty acid?
Oleic acid
What configuration is a double bond in a fatty acid?
Cis configuration
Fatty acids with how many double bonds are most prevalent in the human body?
Fatty acids with 1 double bond
How do carbons appear in a polyunsaturated fatty acid?
3 carbon intervals
Ex: -C=C-C-C=C-
How many double bonds are in a polyunsaturated fatty acid?
2 or more double bonds
What is an example of a polyunsaturated fatty acid?
Linoleic acid
Polyunsaturated fatty acids are NEVER _____.
conjugated
What type of bridge does a polyunsaturated fatty acid create?
Methylene bridge
What plays a significant role in the melting point of fatty acids?
Steric hindrance = causes backbone to bend
The more double bonds in fatty acids = ______ melting point
lower
Which type of fatty acid has a high melting point and is solid?
Saturated fatty acid
Which carbon in a fatty acid is the 1st carbon?
Carboxyl/carbonyl carbon
Which carbon in a fatty acid is the alpha carbon?
Carbon next to the carboxyl/carbonyl carbon
Which carbon in a fatty acid is the beta carbon?
Carbon next to alpha carbon
Which carbon in a fatty acid is the omega carbon?
The last carbon in the chain, farthest away from the carboxyl carbon
Which fatty acids are essential to humans (must obtain from diet)?
Linoleic acid and Linolenic acid
Where does fatty acid synthesis occur?
Cytoplasm of these tissues:
Liver, adipose (fat), CNS, lactating mammary gland
What are the products of acetyl CoA?
1) triglycerides
2) phospholipids
3) eicosanoids
4) energy (ATP)
5) ketone bodies
6) cholesterol (bile salts and steroid hormones)
Where does acetyl CoA for fatty acid synthesis come from?
Mostly from glycolytic breakdown of glucose
What is the major source of acetyl CoA for fatty acid synthesis?
Glucose
What are the conditions that are conducive to fatty acid synthesis?
The ratio of insulin:glucagon is high
What is the net equation of fatty acid de novo synthesis?
8 acetyl CoA + 7 ATP + 14 (NADPH + H+) (right arrow) palmitate (16:0) + 8 CoA + 7 (ADP + Pi) + 14 NADP+ + 6 H2O
What is the rate-limiting step in fatty acid de novo synthesis?
Acetyl CoA carboxylase w/biotin
Acetyl CoA carboxylase requires ______ as a cofactor.
biotin
Which isoforms of acetyl CoA carboxylase (ACC) occur in the liver?
ACCʆ and ACCβ
Which isoform of acetyl CoA carboxylase (ACC) occurs in skeletal muscle?
ACCβ
Which isoform of acetyl CoA carboxylase (ACC) occurs in adipose tissue?
ACCʆ
Which isoform of acetyl CoA carboxylase (ACC) occurs in the heart?
ACCβ
What are the mechanisms used for the short-term regulation of ACC?
Phosphorylation (inactive) and phosphorylation (inactive)
When ACC is phosphorylated it is _____.
inactive
When ACC is dephosphorylated it is ______.
active
Phosphorylation _____ ACC activity.
inhibits
Which enzymes phosphorylate ACC?
AMP-dependent protein kinase & Protein Kinase A
What activates AMP-dependent protein kinase & Protein Kinase A which phosphorylates ACC?
Activated by high glucagon
Which enzyme dephosphorylates ACC?
phosphoprotein phosphatase
What activates phosphoprotein phosphatase which dephosphorylates ACC?
Activated by high insulin
What is a positive effector of ACC in allosteric regulation (long-term)?
Citrate = activation
What is a negative effector of ACC in allosteric regulation (long-term)?
Long-chain fatty acids = inhibition
What does ChREBP stand for?
Carbohydrate-Responsive Element Binding Protein
What is ChREBP?
a major glucose-responsive transcription factor
Where is the expression of ChREMP induced and why is it induced?
Induced in liver in response to increased glucose uptake
ChREBP acts synergistically with which protein?
Sterol Response Element Binding Protein (SREBP)
What happens when ChREBP acts synergistically with SREBP?
Induces lipogenic genes such as ACC and fatty acid synthase
What happens to ChREBP when glucose (basal) concentrations are low?
ChREBP is phosphorylated and resides in the cytosol
What happens to ChREBP when glucose levels are high?
ChREBP is dephosphorylated and translocates to the nucleus where it binds to Carbohydrate Response Elements (ChoREs) to stimulate transcription of lipogenic genes
What happens to ChREBP when glucose levels are normal?
ChREBP is phosphorylated but will not activate lipogenic genes in the cytosol which will not produce fatty acids
What enzyme elongates/lengthens fatty acids?
Fatty acid elongase
Fatty acid elongase uses _____ ____to add 2 carbons at a time in the ______.
Acetyl CoA, mitochondria
Fatty acid elongase uses _____ ____to add 2 carbons at a time in the ______.
malonyl CoA, microsomal (ER)
Fatty acid elongase elongates the chain from the ____.
front
Do acetyl CoA carbons increase or decrease the carbon #?
increase
Where does fatty acid desaturase occur and what does it do?
Occurs in ER and is required to introduce double bonds
What reduces fatty acid desaturase?
NADH
What are the 4 distinct desaturases?
∆9, ∆6, ∆5, ∆4 (act on the 9th, 6th, 5th, or 4th carbons)
What is the minimum chain length required for desaturation?
16-18 carbons
Which desaturase is the main desaturase?
∆9
Elevated levels of which fatty acid is an indication of essential fatty acid deficiency?
Mead acid = 20:3 ∆ 5,8,11
What deficiency causes scaly dermatitis?
Essential fatty acid synthesis
What is the major storage form of fat?
Triaclyglycerides
What are the primary organs of triacylglyceride synthesis?
liver and adipose cells
What is the major fatty acid synthesized de novo?
Palmitate
List the lipogenic genes
1) Acetyl-CoA carboxylase
2) Fatty acid synthase
3) ATP citrate lyase
4) Glucose-6-phosphate dehydrogenase
5) 6-phosphoglucoronate dehydrogenase
6) Malic enzyme
7) Fatty acid desaturase
