Quiz 1 Lipid Metabolism Flashcards
Degradation of fatty acids is termed ____.
Beta oxidation
The major source of carbon for fatty acid synthesis is __.
A. Fats
B. Carbohydrates
C. Protesin
B. Dietary carbohydrates are the majors source of carbon for fatty acid synthesis
Fatty acid synthesis primarily occurs in the ___.
Liver
*also in adipose tissue, brain, kidneys, and lactating mammary glands
The end product of fatty acid synthesis is ___.
Palmitic Acid = 16 carbon molecule
The precursor of Fatty Acid synthesis is ___.
Acetyl-CoA
Acetyl-CoA is made in the ___ but needed in the ___ for Fatty Acid synthesis.
Mitochondria / cytoplasm
Acetyl-CoA is ___ to form ___ during the rate limiting step of Fatty Acid synthesis.
Carboxylated / Malonyl-CoA
How is Acetyl-CoA transported out of the mitochondria?
Acetyl-CoA is converted to Citrate by Citrate Synthase
—>Citrate can exit the mitochondria via a Citrate shuttle
—>Citrate outside the mitochondria can be reconverted to Acetyl-CoA by ATP Citrate Lyase
- Citrate splits into Acetyl-CoA and OAA
- OAA is a precursor for pyruvate and will be re-uptaken into the mitochondria
Regulation of Citrate Lyase:
Activators: Glucose / Insulin
*signals body of FED state and the need for glucose storage
Inhibition: PUFA / Leptin
*signals HUNGRY state and the need for glucose release (therefore, inhibition of glucose storage)
Conversion of Acetyl-CoA to Malonyl-CoA by ___ is the rate limiting step of Fatty Acid synthesis.
Acetyl-CoA Carboxylase
Acetyl CoA Carboxylases uses ___ and ___ as coenzymes during FA synthesis.
ATP / Biotin
Regulation of Acetyl-CoA Carboxylase:
Activators: Citrate / Insulin
*signals FED state and a need for glucose storage
Inhibitors: Glucagon / Epinephrine / high [AMP] / Palmitate / PUFA
*signals HUNGRY or EXERCISE and need for glucose release
*high carb/low fat diet can up-regulate gene expression for it as well
Malonyl-CoA inhibits ___ which is the rate limiting step of FA degradation
Carnitine Acyltransferase
Malonyl-CoA undergoes 7 reactions in the ___ to form Palmitate.
Fatty Acid Synthase Complex (aka. FAS Complex)
FAS Complex is made of ____ each 7 enzyme activities and an acyl carrier protein.
2 identical dimers
The ACP of the FAS Complex has a ___ that assists in moving the substrate along the different enzymatic active sites.
Flexible arm
What pathway generates NADPH?
Pentose Phosphate Pathway (PPP)
Incoming Malonyl-CoA binds to the ___ on the FAS Complex.
Cysteine (-SH) on the PAN acid
*Acetyl-CoA binds to the cysteine on the CYS end for the 1st step
What are the 4 reactions in the FA synthesis catalyzes by the FAS Complex?
- Condensation - forms a beta-ketoacyl group
- Reduction
- Dehydration
- Reduction - forms a 4C fatty acyl group
Insulin always activates a ___ which ___ a substrate.
Phosphatase / de-phosphorylates
*Glucagon and Epinephrine activate kinases (ex: PKA) that phosphorylate substrates
Regulation of FAS Complex:
Activators: insulin / glucogcorticoid hormones (stress) / high carb, low fat diet
Inhibitors: high fat diet / starvation / PUFA
FA chains longer than Palmitate are synthesized in the ___ or the ___.
SER (smooth ER) / mitochondria
- SER uses Malonyl- CoA as carbon donor
- mitochondria uses Acetyl-CoA as carbon donor
Human beings cannot synthesize FA with a double bond beyond ___.
Carbon 9 and 10
*reason why people must consume essential fatty acids
___ stores the most energy in the body.
A. Glycogen
B. TAGs
C. Proteins
B. TAGs in fat and muscle provide the most energy
Where are TAGs made?
Intestinal cells => dietary intake
Hepatocytes and adipocytes => de novo synthesis
Fatty acids must be activated by adding ___ before they can combine with other substrates (like glycerol)
CoA
*this is done by Fatty Acyl CoA Synthetase
Deitary TAGs are broken down into ___ and ___ in the intestinal lumen by lipases.
MAG / FFA
TAG synthesis in intestinal cells forms __ which are released into the lymphatic system before entering the blood.
Chylomicrons
*TAG synthesis in the liver forms VLDL
The only organ that can directly convert glycerol into glycerol 3P is ____.
The liver.
Sources of glycerol in FA synthesis:
Dietary (intestines)
Glucose / Glycerol (liver)
TAG synthesis in hepatocytes (liver) is promoted by ___.
Excess carbohydrates
*reason why consuming carbs can lead to increase in fat
TAG are stored in ___.
Adipocytes
Long chain FA are complexed to ___ to inhibit sticking to the blood vessel.
Albumin
What are the three major lipases involved in breakdown of TAGs?
HSL - hormone sensitive lipase
LPL - lipoprotein lipase
MAG - monoacylglycerol lipase
*ATGL (adipose triglyceride lipase) was recently found to also release DAGs from TAGs in HSL knockout mice
How does Glucagon affect Perilipin in FA release from TAG?
Glucagon promotes phosphorylation of Perilipin
—> Perilipin will release and allow access to TAG in fat droplets
____ prevents access of the lipases to the TAGs within fat droplets
Perilipin
Fatty acids convert to form ___ to be able to pass through into the mitochondrial matrix.
Fatty Acyl Carnitine
What is the rate limiting enzyme for Fatty Acid breakdown?
CPT1 (Carnitine Palmitoyltransferase 1)
*this is inhibited by Malonyl CoA, a substrate made in the RLS of FA synthesis
What are the 4 steps of Beta Oxidation in FA degradation?
- Oxidation
- Hydration
- Oxidation
- Thiolysis
___ is the most common ACAD that inherits defects.
MCAD (Medium Chain Acyl-CoA Dehydrogenase)
When there is an odd number of C, such that Propionyl CoA forms during FA degradation ___ will add a carbon to continue degradation.
Propionyl CoA Carboxylase
*Requires Biotin
VLCFA (very long chain fatty acids) are broken down in ___ while normal FA are broken down in the mitochondria.
Peroxisomes
*1st step is done by FAD-containing Acyl-CoA oxidase which generate hydrogen peroxide!
Disorders in FA-oxidation lead to…
Inability of cells to break down FA for the use of energy
*therefore, main source of energy will be carbohydrate metabolism
Carnitine is an analog of ___. It is not synthesized in the body, though ___ are rich in it.
Lysine / skeletal muscles
Ketone bodies are made from ___.
Acetyl CoA
What are the 3 most common ketone bodies?
Acetoacetate
Beta-hydroxybutyrate
Acetone
Ketone bodies are produced only in the ___.
LIVER (within the mitochondrial matrix of hepatocytes)
Diabetic Ketosis… explain
Diabetes = impairment in the uptake/storage of glucose
—> fatty acid release increases since glucose cannot be used for energy
—>high [fatty acids] = increased formation of Acetyl CoA
—> high [Acetyl CoA] = increased formation of Ketone Bodies
—> Ketone Bodies (are acidic) cause blood pH to drop
—> results in coma/death
