Week 3 - Lipids Flashcards
What is the simplest unit of a lipid?
A fatty acid hydrocarbon
What are lipids stored in ?
In adipose tissue as triacyglycerides
Where does fatty acid synthesis occur?
In the cytoplasm - anabolic pathway
Where does fatty acid oxidation occur?
In the mitochondria - catabolic pathway. Most catabolic, energy-yielding pathways occur in the mitochondria.
What is the terminus of the long hydrocarbon chain of the fatty acid?
A carboxylate group and a methyl end
What are the three major physiological roles of fatty acids?
- building blocks of structural cell membranes
- Steroid molecules; cholesterol, hormones: estrogen/progesterone, bile acids etc and intracellular hormones.
- Fatty acids are steroid molecules; cholesterol hormones
What are triacylglycerols?
Uncharged esters of glycerol
What are unesterified free fatty acids usually associated with?
Albumin
The presence of what in a FA chain makes it unsaturated?
A double bond
If a FA has more than one double bond it is what?
Polyunsaturated
What type of double bond introduces kinks into the FA chain?
Cis double bonds
What increases the melting temperature of FA?
Increased length of chain.
What decreases the melting temperature of FA?
Reduced by cis bonds
What are the two types of LIPID maps classification?
Fatty acyls
Fatty acids and conjugates
What are SCFA’s ?
These are straight chain fatty acids
What is an example of an SCFA that increases appetite regulation?
GPR41, which increases insulin sensitivity, increases leptin and PYY
What can modify gene expression through the methylation of DNA?
Butyrate
What is the difference between free fatty acids and the fatty acids in TAGs/adipose tissue?
Fatty acids in TAGs exist as acyl esters.
Free Fatty acids exist as free, unesterified.
What is saponification?
This is when fatty acids can be hydrolysed by a strong base such as NaOH.
How much of dietary lipif is contributed to TAG?
90% TAG
What is the enzyme in the esophagus that begins digestion of the lipid?
Lingual lipase
What is the enzyme in the stomach that is secreted from the gastric mucosa secretions?
Gastric Lipase
What does lingual lipase and gastric lipase target?
SCFA, MCFA release from TAG
Are active at acidic pH 4.0 - 6.0
When stomach contents are emptied into the duodenum and mix with bicarbonate and bile acid what do they form?
Lipid droplets called micelles
What is the role of pancreatic colipase?
It anchors droplets, colipase restores activity to pancreatic lipase
How is lipid digestion regulated?
By feedback control from the gut hormones
What peptide hormone is produced by the duodenal and jejunum in response to the presence of food?
Cholecytokinin (CKK)
What does CKK do?
- decreases gastric motility
- induces the release of pancreatic digestive enzymes
- induces the gall bladder to contract
What is produced when chyme enters the GI tract and induces bicarbonate release from the pancreas?
Secretin, the bicarbonate neutralises the pH so that the lipases can act
What is the exocrine function of the pancreas?
the secreation of digestive enzymes via the pancreatic duct
What is the endocrine function of the pancreas?
The secretion of insulin, glucagon and other hormones by the islets of langerhans
What is the pancreas responsible for?
glycemic control
What is acute pancreatitis?
- can be caused by gall stones, alcohol abuse, mumps etc
- they have an increased amylase activity in their serum
What is chronic pancreatitis?
This is the consequence of long term inflammation and leads to malnutrition and steatorrhea –> excessive fecal fat
Where do we see Steatorrhea?
Short bowel resection, cystic fibrosis
Chylomicron assembly is impaired in a disorder called?
Zollinger Ellison
What are some of the complications of Zollinger Ellison syndrome?
Malnutrition
NASH - non alcoholic liver disease
NAFLD - non alcoholic fatty liver disease
Short bowel resection (SBR) and parenteral nutrition lead to ?
co-morbidities
intestinal failure
NAFLD
Cirrhosis
What is the regulator protein affected in cystic fibrosis?
CF transmembrane conductance regulator protein is affected
What is one of the treatments in cystic fibrosis for CF transmembrane conductance regulator protein being affected?
Lipase enzyme replacement and vitamin supplementation.
What does the CF transmembrane conductance regulator protein function as?
A chloride channel on the surface of cells: pancreas, lungs, sweat glands
What are the steps involved in fatty acid synthesis regarding the cytosolic acetyl Co A?
- preparation of Malonyl Co A requires cytoslic Acetyl CoA
- Mitochondrial Acetyl CoA cannot move across the inner membrane
- Required citrate shuttle
What is the rate-limiting step of the carboxylation of acetyl CoA to form Malonyl CoA?
Biotin is required as a coenzyme.
High fatty acid AcylCoA
Epinephrine and glucagon
cAMP - activated protein kinase
What promotes the carboxylation of acetyl CoA A to form Malonyl CoA?
High AcetylCoA
Insulin
What is a regulation step that is common to both glycolysis and fatty acid synthesis?
Pyruvate kinase, which is activated when there is an upregulation for it by the ChREBP protein caused by high glucose levels within the liver
What does the ChREBP protein facilitate?
The conversion of excess glucose to pyruvate which is metabolised to acetyl CoA, the main precursor for the synthesis of fatty acids for long term energy storage.
What is the enzyme involved in the elongation of FA chain in 2 carbon increments?
Fatty Acid Synthase
What is the first FA formed, which is 16C?
Palmitate
What does FA synthase do?
- elongation of fatty acid chain in 2C increments
- acts as a dimer
- this protein catalyses 7 different activities
- synthesis is shared between 2 polypeptide chains of the FA synthase enzyme diamer formed
What is the role of Acyl Carrier Protein?
ACP replaces Coa as the entity that binds to nascent fatty acids.
What is the role of 4’ phosphopantetheine?
Acts as a flexible arm to make the nascent FA available to the different activities in FA synthase enzyme
What are the 4 main types of reactions involved in Fatty acid synthase enzyme?
Which steps are repeated until palmitate is formed?
- condensation (growing of chain)
- reduction (carbonyl to hydroxyl)
- dehydration (alcohol to trans-alkene)
- reduction (alkene to alkane)
All steps
What is the role of the thioesterase in Fatty acid synthase?
To cleave the palmitate from ACP
How many thiols participate in fatty acid synthesis?
- thiol from 4-phosphopantetheine in ACP
- thiol from cysteine in FAS
Involves the addition of an acetyl and malonyl group to the FAS enzyme
What are the three reactions that ketobutyryl undergoes in fatty acid synthesis?
- Reduction
- dehydration
- reduction
After each 2C addition, what does the reduction convert the growing chain to?
Saturates fatty acid
How many cycles of condensation and reduction produce the 16C saturated palmitoyl gp bound to ACP?
7 cycles
Where are the two routes to the production of NADPH, catalysed?
- malic enzyme
- PPP
What is involved in the elongation of FA beyond 16C?
Fatty acid elongase complex catalyse the further addition of 2 carbon components from malonyl CoA to palmitate (endoplasmic reticulum)
What types of enzymes are involved in the elongation of FA past 16C?
Elongase Enzymes (specific for each tissue)
What cannot be introduced in humans beyond C9-C10?
double bonds
What are 2 essential fatty acids for humans?
Linoleate and linolenate
What is needed to accept fatty acids in the synthesis of TAGs?
Glycerol 2 phosphate
Adipose tissue lack glycerol kinase, what do they use instead in the synthesis of TAG?
DHAP and glycolysis
What must happen to FA before addition to G3P?
FA must be activated to acyl CoA forms for addition to G3P It must have an attachment to CoA to make TAG
What are the two steps which happen when a FA has been activated?
Acyltransferases transfer FAs from CoA
Phosphatase removes Phosphate => diacylglycerol
Another Acyl FA is added; acyl transferase –> triacylglycerol.
Are the three FA in a tag of the same type?
Not usually
In the liver TAG is packaged in lipoprotein particles called?
VLDL
What is TAG broken down to?
Acetyl CoA
In the catabolism/Beta oxidation of FA what is produced?
- Acetyl CoA
- reducing power is given to NADH
- location: mitochondria
Anabolism/Biosynthesis of fatty acid requires?
Requires malonyl CoA and acetyl CoA and a reducing power from NADPH along with it happening in the cytosol in animals and in the chloroplast in animals
Why do FA carry less water?
As they are non-polar.
What lipase is involved in the release of fatty acids from TAG?
Hormone-sensitive lipase
FA CoA are formed by which enzyme?
Long chain fatty acyl CoA thiokinase
What is the name of the two carnitine transporters which are responsible for bringing the FA -CoA molecule across the CoA impermeable inner mitochondrial membrane?
- carnitine palmitoyl transferase I
- carnitine palmitoyl transferase II
What is a major regulator of FA synthesis and breakdown in the cytosol?
citrate - high energy indicator
Where does the beta oxidation of FA occur?
In the mitochondrial matrix. Involving the sequential removal of 2C from acyl chain.
What are the major products of Beta oxidation?
Acetyl CoA
FADH2
NADH
What does the liver use to create ketone bodies which are generally exported for use in other tissues?
Acetyl coA
What is the energy yield from beta-oxidation?
33 ATP equivalents
What is the energy requirement of beta oxidation?
49 ATP equivalents
What is the major regulatory enzyme in beta oxidation?
Acetyl CoA availability
What is the major regulatory enyzme in FA synthesis?
Acetyl CoA carboxylase
What can also regulate DA synthesis, beta oxidation, peroxisome beta oxidation and TAG synthesis?
PUFAs
In peroxisomal FA degradation what is not produced?
FADH2 (used to produced H2O2) is produced, NADH is not produced.
What do odd chain fatty acids produce?
Propionyl CoA
Saturated FA have what kind of geometry?
Trans Geometry
Unsaturated FAs and PUFA have what kind of geometry?
Cis Geometry, they also yield less energy as they are partially oxidised and there is less FADH generated – leading to propionyl CoA being generated
The liver can convert acetyl CoA derived from FA to ketone bodies, what are the 3 main ketone bodies?
Acetoacetate
3-hydroxybutyrate
Acetone
What are 3 important characteristics about ketone bodies?
- water soluble
- produced when ACetyl CoA levels are in excess
- can be used by the brain if blood levels are high enough
What is high ketolysis associated with?
Type I diabetes
Ketogenesis is catalysed by ?
HMG CoA synthase, a rate limiting step.
Why is ketolysis important?
It is important during fasting.
As liver cells lack thiophorase.
In the peripheral tissues, thiophorase can be used to go back into the TCA cycle or back to make acetyl CoA