Lipid Metabolism Flashcards
How is Acetyl CoA transported from mitochondria to cytoplasm
It is converted to citrate in TCA cycle, then transported out via citrate transporter, then converted to Acetyl CoA and Oxaloacetate by ATP citrate lyase
Allosteric regulators of citrate lyase include
Glucose, Insulin ++
PUFA, Leptin –
What is the rate limiting step in FA synthesis
Conversion of Acetyl CoA to malonyl CoA by acetyl CoA carboxylase
What is the series of reduction/condensation/dehydration events in FA synthesis
Condensation, reduction, dehydration, reduction
Gene expression of FA synthesis genes is activated by what type of diet
High carb, low fat
Allosteric regulators of Acetyl CoA carboxylase
Citrate, insulin +
Glucagon, epinephrine, AMP, PUFA, palmitate -
Phosphorylation regulators of Acetyl CoA carboxylase
Insulin ++ activates protein phosphatase
Epinephrine/Glucagon – via PKA
AMP – via AMP kinase
Where are fatty acids elongated, and what carbon donor is used for each area
SER- Malonyl CoA is carbon donor
Mitochondria- Acetyl CoA is carbon donor
TAG synthesis in intestinal cells vs liver cells vs adipose- promoted by what in each area?
Intestinal- dietary TAGs, leave as chylomicrons
Liver- Excess carbs, leave as VLDL
Adipose- excess carbs and fat, leave as VLDL
What is HSL and how is it regulated
Hormone sensitive lipase- Breaks down TAGs
Phosphorylated/activated by glucagon/epinephrine
Insulin dephosphorylates via PPI
Perilipins do what
Regulate lipolysis by controlling physical access to HSL
PKA phosphorylates perilipin which then allows association with HSL
How do fatty acids get into mitochondria
Fatty acid is attached to CoA in order to get through outer mito membrane (not permeable to FA)
- Then converted to FA-carnitine to get through inner mito membrane (not permeable to FA-CoA)
- Short/medium chain FA can diffuse through mito membrane, while long/very long cannot
FA-CoA synthetase location/function
Located on outer mitochondrial membrane
Activates LCFA using ATP to form FACoA
Carnitine palmitoyltransferase-I (carnitine acyltransferase) location/function
Intermembrane space of mitochondria
Transfers fatty acyl from FA-CoA to carnitine
-Rate limiting enzyme in FA breakdown
-Inhibited by malonyl CoA
Carnitine palmitoyl/acyl-transferase II location/function
Inner mito membrane
Transfers FA from carnitine to CoA
FA-CoA now in mito matrix
What are the 4 steps of beta-oxidation and their enzymes
Oxidation- Acyl CoA dehydrogenase
Hydration- Enoyl CoA hydratase
Oxidation- B hydroxy acyl CoA dehydrogenase
Thiolysis- Acyl CoA acyl transferase
VLCFAs (greater than 20c) are metabolized where
In peroxisomes
With odd numbered fatty acids, which molecule finally ends up entering the TCA cycle
Succinyl CoA
What two enzymes are required for unsaturated fatty acid breakdown
Reductase (reduce double bond)
Isomerase (move disruptive bond)
MCAD deficiency
Impairs breakdown of MCFAs
Leads to secondary carnitine deficiency, due to excessive excretion of MCA carnitines in urine
C8 FA accumulates in liver, poisonous, elevated levels of ammonia
Name 3 ketone bodies and where they are produced
Acetoacetate
B-hydroxybutyrate
Acetone
Only produced in liver
List off energy sources from the first one used to the last one used when fasting
Glucose Glycogen Gluconeogenesis in liver (new glucose made) TAGs Ketone bodies AAs/glycerol
Ketoacidosis
Occurs when glucagon/insulin ratio is increased, favoring FA breakdown
Increased acetyl CoA in hepatic mitochondria
Increased gluconeogenesis, reduced OAA, increased ketone bodies-blood pH lowers
