Fat Synthesis Flashcards
What are the two transport mechanisms for glucose in a cell?
Sodium independent facilitated transport system and Sodium-monosaccharide co-transport system (SGLT)
This glucose transport mechanism utilizes GLUT and moves glucose down a concentration gradient.
Sodium independent facilitated transport system
This glucose transport mechanism is ATP dependent, transports glucose against a concentration gradient and is found in the epithelial cells of intestines, renal tubules, and choroid plexus.
Sodium-monosaccharide co-transport system (SGLT)
This glucose transporter transports glucose, galactose, and fructose into the liver, kidney, and pancreas beta-cells and is insulin independent
GLUT 2
This glucose transporter transports glucose into muscle and adipose tissue, is stimulated by insulin and low energy charges (AMPkinase), and deals with facilitated diffusion
GLUT4
As long as the concentration of glucose is lower in muscle (and transporters are available) where will glucose go?
Glucose will move from the blood to the muscle
By adding a ____ to glucose, the glucose concentration in muscle remains low and glucose keeps coming in.
Phosphate
When muscle ____ is low, glucose 6 phosphate runs through glycolysis, prep step and Krebs to make more ATP.
Energy charge
When muscle glycogen is low, _____ is converted into glycogen.
Glucose 6 phosphate
About 90% of insulin-stimulated glucose uptake occurs where?
Skeletal muscle
Exercise increases the number of what glucose transporter in skeletal muscle?
GLUT4
When glucose is consumed and transported to muscle, if the muscle is full of glycogen what happens?
The glucose goes to the liver
When glucose is consumed and transported to muscle, if the muscle is not full of glycogen what happens?
Glucose is stored as glycogen
How do muscles say “no” to incoming glucose?
- High energy charge will inhibit PFK
- Glucose 6 phosphate accumulates
- Hexokinase is inhibited
- Inhibition of glucose 6 phosphate causes glucose to accumulate, which stops the flow of glucose from blood to muscle
This enzyme has a lower affinity for glucose, is not inhibited by its product, stimulated by insulin, and is stimulated by fructose.
Glucokinase
What primary tissues are involved with the synthesis of fatty acids?
- Liver
- To a lesser extend adipose tissue and kidneys
- Mammary glands during lactation
Where does the synthesis of fatty acids occur?
Cytosol
What are the “ingredients” for the synthesis of fatty acids?
- Two carbon pieces (acetyl)
- Electrons (NADPH)
- Energy (ATP)
What are the steps of fatty acid synthesis?
-Sugar runs through glycolysis
-Prep step to make acetyl CoA
-Kreb’s cycle
-Citrate is made
-Too much ATP causes Kreb’s cycle to slow
Citrate is kicked out of the mitochondria
-Two carbon acetyl CoA is given back to start fat synthesis
-Acetyl CoA is converted to malonyl CoA
-Malonyl CoA is given to fatty acid synthase (FAS), which adds them to a growing fatty acid
What enzyme in the Kreb’s cycle is inhibited by ATP, resulting in citrate accumulating?
Isocitrate dehydrogenase
What enzyme converts acetyl CoA to malonyl CoA?
Acetyl CoA carboxylase
Coenzyme: Biotin
What is the rate limiting step of fatty acid synthesis?
Acetyl CoA carboxylase
What is acetyl CoA carboxylase activated by? Deactivated by?
Citrate; Long chain fatty acyl CoA
Short term regulation of acyl CoA carboxylase involves what type of process? What are some examples?
Reversible phosphorylation
- AMPK phosphorylates and inactivates acyl CoA carboxylase (ACC)
- Epinephrine and glucagon increase cAMP, which phosphorylates and inactivates ACC
- Insulin dephophorylates and activates ACC
What are some ways acyl CoA carbocylase (ACC) is regulated over the long term?
- High calorie/high carb diet increases ACC synthesis which increases fatty acid synthesis. Low calorie/low carb diet does the opposite
- Upregulated by insulin: increased response/increased receptors (sterol regulatory element-binding protein (SREBP-1))
What stimulates acetyl CoA carboxylase?
Citrate and Insulin
What inhibits acetyl CoA carboxylase?
- Malonyl CoA
- Palmitoyl CoA
- Epinephrine
- Glucagon
This substance is involved in type II diabetes and inhibits ACC leading to activation of AMPK, a decrease of SREBP-1, and a lowering of blood glucose.
Metformin
This multienzyme complex contains an acyl carrier protein, is similar to coenzyme A, and has a terminal thiol group at the end of an “arm”.
Fatty acid synthase
What are the first three reactions that set the stage for fatty acid synthesis?
1) Acetyl group (2C) is transferred to the thiol group on ACP by acetyl CoA-ACP acetyl transacylase
2) Acetyl group moved to a temporary holding site on a cysteine residue on the enzyme
3) Malonyl group (3C) transferred to the thiol group on ACP by malonyl-CoA-ACP transacylase
What are the last four reactions of fatty acid synthsis?
- Condensation: Acetyl ACP and Malonyl ACP are converted to Acetoacetyl-ACP by beta-ketoacyl-ACP synthase
- Reduction: Acetoacetyl-ACP is converted to D-3-hydroxybutyryl-ACP by beta-ketoacyl-ACP reductase
- Dehydration: D-3-hydroxybutyryl-ACP is converted to crotonyl-ACP by beta-hydroxyacyl-ACP dehydratase
- Reduction: crotonyl-ACP is converted to butyryl-ACP by enoyl-ACP reductase
After the last four reactions of fatty acid synthesis (condensation, reduction, dehydration, reduction) we have a four carbon molecule (butyryl). What happens to this molecule?
It is transferred to a holding site (cysteine), another malonyl is added, and the steps are repeated until it is 16 carbons long (Palmitate, 16:0)
Release of the fatty acid is the last step in fatty acid synthesis. How is this accomplished?
The thioester bond of palmitoyl-S-ACP is cleaved by palmitoyl thioesterase releasing the saturated palmitate.
Where does the NADPH needed for fatty acid synthesis come from?
- Pentose phosphate pathway
- Malate–>pyruvate in the cytosol
How is palmitate elongated?
Elongases. NADPH is required
How is palmitate desaturated?
Desaturases (adds double bonds)
Can humans create double bonds beyond the 9th-10th carbon?
No
What is the primary site for fructose disposal?
Liver
What enzymes are essential for fructose metabolism and are highly expressed in the liver?
Fructokinase and triokinase
