Fatty Acid Biosynthesis Flashcards
Where is majority of required fatty acids supplied in ?
Diet
Where is the pathway present ?
In liver, brain, kidney, mammary gland and adipose tissue for de novo synthesis from 2-carbon compounds
When is the pathway used ?
In conditions of excess energy in particular carbohydrate intake
What is converted fatty acids stored as ?
Triaclyglycerols
What is the 2 stage process in the pathway ?
Preparation of precursor malonyl-CoA and elongation of fatty acid
Fatty acid synthesis occurs in ?
The cytosol, consistent with being a reductive process
Since fatty acid synthesis occurs in the cytosol, acetyl coA needs to ?
Be shuttled out of the mitochondria
What allows acetyl coA to cross the mito membrane?
Citrate can interact with a carrier
What does fatty acid synthesis require ?
Both stages require:
Acetyl-CoA and multienzyme complex
- Preparation of malonyl-CoA by acetyl CoA carboxylase
- Elongation of FA chain by fatty acid synthase
Explain Acetyl-CoA carboxylase ?
- Acetyl-CoA converted to malonyl CoA
- Biotin dependent enzyme
- Its subunits serve as
1. biotin carboxylase,
2. transcarboxylase
3. biotin-carboxyl carrier protein - Enzyme synthesised as inactive protomer – regulated by citrate and palmitoyl-CoA
- Reaction occurs in two stages
1. Carboxylation of biotin (+ ATP)
2. Transfer of carboxyl group to acetyl-CoA - Carboxylation of acetyl CoA is first committed step of FA synthesis
Acetyl-CoA carboxylase is regulated ?
By phosphorylation
What does the cytosolic pathway lead to ?
To the synthesis of saturated fatty acids, with the main product being the 16 carbon fatty acid palmitate
Elongation reactions are catalysed by ?
Enzymes located on the cytosolic face of the endoplasmic reticulum membrane. Malonyl CoA acts as the donor
Reduction reactions also occur at ?
The ER membrane to produce unsaturated fatty acids
Explain Fatty acid elongation ?
- FA elongation occurs on ER
- Requires fatty acid elongase
- Again occurs by addition of malonyl CoA
- Similar reactions to FA synthase except FA attached to CoA rather than ACP
Very long chain FA produced in brain which increases ?
Rapidly during myelination producing the FA required for sphingolipid production
In both liver and adipose tissue, TAGS produced by a ?
Pathway involving glycerol-3-phosphate
The origin is dependent on the tissue ?
- In liver - glycerol
- In adipose tissue - glucose
- In both - intermediates are G-3-P & Phosphatidic acid
Explain Cholesterol ?
- Mol wt 386 kDa
- almost completely saturated – only 1 double bond
- Low solubility in water
- Precursor of bile acids, steroid hormones and vitamin D
- Typical diet contains 500mg daily, 30-60% of this absorbed from gut
- Humans synthesise 1g daily
- Only 30% in free form, majority esterified to long chain fatty acids
All human cells have ability to make cholesterol. Where is the major site of synthesis ?
The liver
What does 1 cholesterol require ?
- 18 acetyl CoA
- 36 ATP
- 16 NADPH
What is the unique starting compound in this pathway?
Mevalonic Acid
Producing Cholesterol ?
- HMG-CoA reductase enables the cell to make cholesterol
- Cholesterol is released into the blood
Limiting Cholesterol production ?
- Cholesterol-lowering statin drugs work by inhibiting HMG-CoA reductase
- Cholesterol production is blocked, lowering levels of cholesterol in the blood
Adipose tissue are ?
Hormonally active
Adipokines (leptin, adiponectin, resistin, growth factors and inflammatory cytokines generated by ?
Adipocytes
What are the main adiposity signals ?
Leptin and insulin (synthesised by pancreas)
Amount of leptin proportional to ?
Body fat content
Leptin decreases ?
Appetite and increase thermogenesis
After a moderate-high carbohydrate meal, fatty acid oxidation in liver is ?
Suppressed and synthesis is promoted
During starvation fatty oxidation in liver is ?
Stimulated and fatty acid synthesis is suppressed
Increased blood flow to muscles due to ?
Local mediators and β-adrenergic stimulation of
vascular smooth muscles
Glycogen breakdown and some steps in glycolysis are greatly stimulated by ?
Stress
