YOUNGER BLOCK 2 Flashcards
Unsaturated FA
Double bonds present
- cause kinks
- three carbon intervals
- reduces melting temp, increases fluidity
Why do membrane phospholipids often contain double bonds?
Because they are LCFA (the longer the chain, the higher the melting temp) and needs the double bonds there to lower the melting temp and increase fluidity
What are 2 essential FA?
- a-linolenic acid
- linoleic acid
Arachidonic acid
Becomes essential is linoleic acid is deficient in the diet
Linoleic acid
- essential FA
- omega 6
- precursor for other omega 6 FA
- arachidonic acid becomes essential if this is deficient
A-linoleic acid
- precursor for omega 3 FA
- important for growth and development
- essential FA
Arachidonic acid
- substrate for prostaglandin
- becomes essential id linoleic acid is deficient in diet
FA less than 12 carbons
-short and medium chain
FA greater than 22 C
VLCFA
Where are LCFA synthesized>
de novo synthesis
Where are VLCFA synthesized ?
Brain tissue
Dietary lipids
- TAG
- phospholipids
- free FA
- cholesterol
- cholesterol esters
Acid lipase
- lingual lipase
- gastric lipase
- target TAG containing short and medium chain FA
- can get through to blood stream without micelle
What are the two complimentary actions of emulsification in the small intestines?
- mechanical agitation
- bile salts secretion
- detergent
- don’t coalesce
- allows pancreatic enzymes more surface area
What are the pancreatic enzymes responsible for TAG digestion
- pancreatic lipase
- colipase
Phospholipase A2
- phospholipid digestion
- removes the fatty acid from position 2 from arachidonic acid
What do gut endocrine cells sense?
CCK senses lipids and proteins, causes reduction of gut motility
Secretin senses low pH and secretes bicarbonate
Micelles
- amphipathic lipids
- DEAK
How do short and medium chain FA get into blood stream?
They don’t need a micelle
Fatty acyl-CoA synthetase (thiokinase)
-loads fatty acyl-CoA for entry into chylomicron
Chylomicron
- ER—lymph system—-blood
- contain B-48
- carries neutral lipids such as TAG and DEAK vitamins
Lipoprotein lipase
- clip FA from chylomicron
- synthesized and secreted by muscle and adipose
Remnants interact with liver cells and are endocytosed, this is where the vitamins get absorbed into the body
Lipid malabsorption
Poor digestion such as inability to secrete the proper amount of bile.
Shortened bowel disease
Cystic fibrosis
- cant take up fat soluble vitamins
- pancreatic insufficiency, significant reduction in dietary calories, decrease fat soluble vitamin up take
- treatment includes: enzyme replacement, and fat soluble vit supplements
De novo synthesis
- well fed
- cytosol of liver and mammary glands of lactating mammals
- cytosolic acetyl CoA is carbon source for growing FA chain (originate in mitochondria)
- energy source: ATP and NADPH
Which membrane of the mitochondria is hard to get across?
The inner mitochondrial membrane
ACC
- dimers in cytosol
- coalesce to larger molecule which is active
- takes CO2/energy and carboxylase acetyl CoA to malonyl CoA
- RATE LIMITING STEP
Presence of citrate
Signals ACC
Short term regulation of ACC
- AMPK reversibly phosphorylates and inhibits ACC
- LCFA presence also inhibits it (substrate)
Long term regulation of ACC
- prolonged high calorie, high carb increases ACC synthesis
- low calorie or high fat diet reduces ACC synthesis
FAS
- multifunctional dimeric enzyme
- 7 different enzymatic activities
- acyl carrier protein (ACP)
- holding site for cysteine
2 C from malonyl CoA
ATP
NADPH
Predominant source of the NADPH required for FA synthesis
HMP shunt
Palmitate
Elongated at the smooth ER
Reduction of NADPH
2 C from malonyl CoA
Desaturation of FA chains
Add double bonds to maintain fluidity at body temp
Carbon 2 on TAG
Unsaturated FA of varied length
Where is TAG generated ?
In liver and adipose
TAG generation in liver
Glycerol kinase converts free glycerol to glycerol phosphate simply by adding a phosphate group
What do chylomicrons deliver?
Exogenous dietary lipids
What do VLDLS deliver?
De novo synthesized lipids
Adipose lipase
-constitutive, low level release of FA
Hormone sensitive lipase
- major role in regulated TAY lipolysis and release
- much more than adipose lipase
- heavily influenced by insulin
What is the major pathway for obtaining energy from FA
B-oxidation in the mitochondria
FA must be in the fatty acyl CoA
Products of B oxidation
Acetyl CoA, NADH, FADH2q
Carnitine shuttle
- imports LCFAs into the mitochondria
- CATI on outer mitochondrial membrane acyl groups transferred from CoA to carnitine. Regulated by malonyl CoA
- CATII on matrix side acyl group transfer from carnitine to CoA
CAT I inhibition
Malonyl CoA
-preventing LCFA transfer from CoA to carnitine
Source of carnitine
Diet
Synthesized in liver/ kidney
Where is most of the carnitine
Skeletal muscle
Secondary carnitine deficiency
- liver disease
- malnutrition
- dialysis
- pregnancy
Primary carnitine deficiency
congenital deficiencies
CAT I and CAT II defect
Energy molecules for B oX
NADH
FADH2
Acetyl CoA–produce ketone bodies in liver to be used by peripheral tissue
What vitamin is required for odd number of carbon degeneration?
Vitamin B12
Saturated or unasturated FA release less energy?
Unsaturated
-require additional enzymes
MCAD deficiency
Decreased oxidation of 6 to 10 carbon FA
-hypoglycemia
Ketone bodies
- produced in liver from B-oxidation derived acetyl CoA
- acetoacetate and 3-hydroxybutarate transported in the blood to peripheral tissues
- peripheral cells convert ketone bodies back into acetyl CoA, a substrate for the TCA cycle
- decrease the demand on blood glucose
Hypoketosis
-fatty acid oxidation disorder due to decreased acetyl CoA availability
Hypoglycemia
-fatty acid disorder due to increased reliance on glucose for energy
HMG CoA synthase=
- rate limiting step in ketone body synthesis and is present only in the liver to significant amounts
- makes 6-C chain to make ketone
Can liver uses ketone bodies as fuel?
No because it lacks thiophorase
-extrahepatic cells having mitochondria can conduct this process
Imbalances in use and production of ketone bodies
Cause ketone ketone bodies to rise
- blood (ketonemia)
- urine (Ketonuria)
How can ketoacidosis be caused?
Fasting
-decreases blood volume increases H+ concentration causing severe acidosis
Why is thromboxane synthesis more severely affected by NSAIDs and how does it affect coagulation?
Inhibits the COX step in the formation of both prostacyclin and thromboxanes
-platelets cannot synthesize new COX because no nucleus and significantly limits the thermogensis potential
Glucocorticoids and inhibited phospholipase A2
- inhalers
- steroidal anti-inflammatory drug
- promotes gene level up-regulating of phsopholipase A2 inhibitor
