Flashcards in Metabolism 2 - Part 1 Deck (159):
What is the term for esterified fatty acids?
Name 7 classes of lipids
Name a 2nd messenger lipid
Chains on the hydrocarbon part of fatty acids vary from ____ to ____ in length.
A fatty acid is nonpolar
carboxyl end is an acid
A molecule (like a fatty acid) that has both hydrophilic and hydrophobic characteristics is...
What is the most common Fatty Acid in the body?
How many carbons?
Describe the 2 notations counting carbon saturation in fatty acids
From COOH = delta (superscript)
From omega = n-6, etc
Where are the alpha, beta, and omega carbons in a FA chain?
alpha - one away from C1 (the carboxylic Carbon)
beta - two away from C1
omega - the last C
Palmitate is ______
Pamitoleic is ______
Mammalian enzymes cannot make a double bond more than ____ carbons away from the carboxylic end.
What is the name of an essential fatty acid required in diet
(comes in omega 3 and 6 forms)
Why do omega 3 and omega 6 pathways compete with each other?
They share the same enzymes
What do essential fatty acids like linoleic acid serve as a precursor for?
What effects do eicosonoids have on the cell?
What is an example (precursor linoleic acid)
What is the difference between a simple and a mixed triacylglycerol?
simple - has same carbon chains
mixed - has different (saturation levels/length) chains
What molecule is at the crossroads between making triacylglycerols and phospholipids?
Why are triacylglycerols such a good form of energy storage?
Reduced and Anhydrous
Name 5 things fatty acids are precursors to?
Short, medium, and long Fatty Acid lengths:
Short - 2-5 C's
Medium - 6-12 C's
Short and unsaturated Fatty Acids tend to be:
Long and saturated Fatty Acids tend to be:
PUFA and MUFA tend to be oils. What do they stand for?
Polyunsaturated fatty acids
monounsaturated fatty acids
Where are trans fats made?
industrial hydrogenation processes
body lacks enzymes to break down
(only breaks cis)
What is the major intermediate found both in triacylglycerides and phospholipids?
What are 2 essential fatty acids?
Linoleic and alpha linoleic acid
(remember - precursor to eicosonoids)
Arachidonic acid is synthesized entirely by what fatty acid?
Linoleic Omega 6 form
What two things distinguish apple (as opposed to pear) shape?
Metabolically active and dangerous
Where does lipid digestion begin?
in mouth (Lingual Lipase)
but this process isn't efficient in adults
What type of lipid digestion occurs in the stomach (what enzymes are involved)?
Acid-stable Lingual lipase (slow)
Gastric lipase (pH 7 optimal - only useful for SCFA and medium chain fatty acids)
What converts macroscopic fat cells into micelles?
What are bile acids made from and what are they secreted as?
secreted as taurine and glycine salts
Name the 3 bile acids
What is the process of bile acid reabsorption to the liver via the portal vein called?
What two steps happen to create fatty acids in the intestine?
Bile salts break down into micelles
Pancreatic lipase break into FA's
(goes into the unstirred layer)
What is the small peptide hormone released by the jejunum in response to chyme?
What are 3 functions of Cholecystokinin?
Stimulates gall bladder release
Releases pancreatic enzymes
Slows digestion from stomach (gastric emptying)
What is released into the duodenum in response to low pH of chyme?
What does it induce?
induces pancreas to release bicarbonate (buffer)
What is the most important (for this class) pancreatic enzyme?
What does it do?
What are two others?
Pancreatic Lipase (leaves middle leg from TAGs)
What stabilizes the lipid-water interface interactions (surface area of which digestion depends) of Pancreatic Lipase?
(also secreted by pancreas)
Procolipase is cut by trypsin to form Colipase, the other end is a 5 AA sequence called Enterostatin that acts as a satiety signal. What is that sequence?
(damn near palindromic)
What substrate and enzyme create cholesterol in the intestine?
Cholesteryl ester + Cholesteryl esterase (hydrolyzes)
= Cholesterol + Fatty acid
The proenzyme of Phospholipase A2 is activated by...
Phospholipase A2 (after trypsin activation) pathway first removes FA at C2, then C1
What are the substrates of this rxn?
phospholipid (remove C1) > lysophospholipid (remove C2) > glycerophosphoryl base
What Beta-Clam structure protects the cell from the soapy nature of fatty acids and quarantines it inside the cell before repackaging and exit to the lymphatic?
What 2 steps occur in an intestinal cell after FA absorption that need to occur before fat leaves?
FA > Fatty acyl CoA > Chylomicron (with polar outer layer)
What types of fatty acids do not need to be repackaged in the intestinal mucosal cell?
What carries them around the body?
Short and Medium chain fatty acids
What happens to Fatty Acids and cholesterol before they are repackaged into chylomicrons?
FA's re-esterified into TAG's
Cholesterol re-esterified into cholesteryl ester
Cholesteryl ester > cholesteryl esterase > cholesterol
Phophatidylcholine > Lipase > glycerylphosphorylcholine
Triacylglycerol > pancreatic lipase > 2-monoacylglycerol
What is lingual lipase's target?
Why is Gastric lipase useful if its optimal pH is around 7?
It's only really used in babies.
What does pancreatic lipase break a TAG into?
2 Fatty Acids
What peptide hormone is responsible for stimulating the digestion of fat and protein?
(also acts as a hunger suppressant)
What does FACS stand for?
Fatty Acyl CoA Synthetase
remember: works on both FA>TAG and sterol>steryl
What is found in a chylomicron?
What is found on a chylomicron?
Apo B48, phospholipid, free cholesterol, ApoA
What hydrolyzes chylomicrons?
Lipoprotein Lipase (LPL)
Where are FFA's, monoacylglycerides, and cholesterol found?
Where are TAG's, cholesteryl ester, glycerylphophorylcholine found?
mucosal intestinal cells
Trace chylomicron to blood
Intestinal mucosal cells > lymph > Subclavian vein via thoracic duct > superior vena cava
List the lipoproteins from biggest to smallest
What is the major difference between a chylomicron and VLDL?
Chylomicron carries dietary fat
VLDL carries synthesized fat
What does the shell of a chylomicron contain?
(Apo B48 and Apo A)
What is a known marker for Alzheimers?
allele marker for ApoE
What docks to lipoprotein lipase in the capillary?
Where do Chylomicrons pick up ApoCII and ApoE?
After ApoCII activates lipoprotein lipase, where do TAG's generally go?
Where does glycerol go?
Heart, muscle, adipose tissue
How is the chylomicron remnant taken up by the liver?
Fatty Acid + CoA + ATP >
(this is the rxn allowing cell to hold on to FA)
Acyl CoA + AMP + PPi
In the liver, what are excess fats (and indirectly carbs) packaged into?
Name 5 apolipoproteins in VLDL.
What lipoprotein do nascent VLDL have on their surface?
Where does VLDL pick ApoC-II and ApoE?
remember: ApoC-II interacts with lipoprotein lipase to release FA's from TAGs into cells)
How is LDL formed?
What happens to its surface proteins?
What is left over in LDL?
VLDL releases TAGs until its IDL then LDL
Apo C-II and ApoE are returned to HDL
What is the primary function of LDL?
Delivery of Cholesterol
How does LDL bind cells to deliver cholesterol?
What appears to block this process (thus raising blood cholesterol levels)?
ApoB-100 receptor mediated endocytosis
Saturated fatty acids
What 2 apolipoproteins does HDL provide (act as a reservoir) for chylomicrons and VLDL?
ApoC-II and ApoE
How does HDL scavenge cholesterol from membrane lipid lecithin?
A-1 activates LCAT (Lecithin Cholesterol Acyl Transferace - aka PCAT)
converts membrane lipids FA's to cholesterol
What exchanges choleteryl ester from HDL for TAG from VLDL?
Cholesteryl ester transferase protein (CETP)
Apolipoproteins on a:
ApoB48, ApoCII, ApoE (latter 2 from HDL)
ApoB48, ApoE (latter gets into liver, ApoCII taken back by HDL)
What is the adipose, heart , muscle, live distribution of chylomicrons?
80% - adipose, heart, muscle
20% - liver
Apolipoproteins associated with:
ApoB48 (and ApoCII, ApoE from HDL)
ApoB100 (and ApoCII, ApoE from HDL)
Which lipid is highest in cholesteryl esters?
highes in protein/lipid ratio?
What does HMG CoA reductase do and what downregulates its actions?
makes cholesterol in the liver
LDL binding liver downregulates
How is saturated fat interference at the HDL binding site at the liver a double whammy?
Cholesterol remains in blood
more cholesterol made in liver because HMG CoA reductase keeps churning out cholesterol
Where are the exceptions to fat being the dominant form of energy?
Brain and RBC's
When does ketogenesis take place?
When Acetyl CoA is high and Oxaloacetate is low
What makes and uses ketone bodies?
(not really ketones, but organic acids that drop pH)
Liver makes but does NOT use.
Everything else uses.
What favors ketogenesis?
low insulin/glucagon ratio
(a lot of glucagon)
When you're hungry, what stimulates the liver for GNG?
what stimulates the cells for TAG breakdown?
Glucagon talks to the liver
Epinepherine talks to the cells
What does PKA, from the Adenelyate Cyclase pathway, activate by phosphorylation?
Breakdown of TAG to DAG
(then other lipases break down further)
What is the initial effector of the Adenelyate Cyclase pathway leading to TAG breakdown?
Hormone (glucagon and epinepherine)
This is a Hormone Sensitive Lipase
What is the fate of released glycerol in TAG breakdown?
Liver GNG or glycolysis
(both in liver)
In the cell, where does building and breaking down fat occur?
Build - in cell
Break down - in mitochondria
Trace fat changes from outside the cell to the mitochondrial matrix.
TAG outside > lipoprotein lipase breaks to FFA > FA inside cell > Fatty acyl CoA (via FACS) > Acyl Carnitine (crosses into mitochondria) > Fatty acyl CoA
Beta oxidation from here
What size Fatty Acids go through the Carnitine Cycle to enter the mitochondria?
Where do they go if they're bigger?
What inhibits carnitine acyltransferase (CPT-1) from transfering Fatty acyl residues to acyl carnitine?
(a substrate of fat synthesis)
What is exchanged in a 1:1 ratio through a translocase at the IMM?
Fatty acyl carnitine for carnitine
Once in the Matrix, what is responsible for changing Fatty acyl carnitine back to Fatty acyl CoA
Carnitine Acyltransferase II (CPT-II)
What does Palmitate (16:0) yield upon Beta-Oxidation?
8 Acetyl CoA
What does each turn of Beta Oxidation yield?
1 Acetyl CoA
(each pass takes off 2 Carbons)
What is the first step (most important) Enzyme in Beta-Oxidation?
Where are very long chain FA catabolized?
What are the final products in Long Chain Fatty Acid Oxidation?
Are NADH and FADH2 produced in this process?
(both metabolized in mitochondria)
What enzyme changes H2O2 to Water and oxygen in the peroxisome?
What is the odd numbered Fatty acid of metabolism?
What is its coenzyme?
How are unsaturated fatty acids metabolized?
Isomerized, Oxidized, and miss the first redox rxn
What are unsaturated fatty acids isomerized to?
Trans (delta 2) Enoyl CoA
What is the most important (for this class) ketone body?
What are the 3 ketone bodies?
Where are they made?
Acetoacetate (this makes two products, which are)
Made exclusively in the liver (these are basically mobile acetyl CoA)
What does uncontrolled ketone body formation lead to?
What is the starting product of Ketogenesis and where does it occur?
2 Acetyl CoA's
Where does Fatty Acid synthesis occur?
(organs and location in cell)
Liver and lactating mammary glands
How many Acetyl Coa does it take to make Palmitate?
Where is the Acetyl CoA used in palmitate synthesis produced?
Where is it used?
Produced in the mitochondria
Used in the cytosol
How does Acetyl CoA get out of the mitochondrial matrix to undergo fatty acid synth?
Combines with oxaloacetate to form Citrate.
Citrate leaves the Mitochondria
Once in the cytosol, citrate breaks down into oxaloacetate and Acetyl CoA (and uses 1ATP in the process - there's your skin in the game)
What pathway provides NADPH for FA synth?
Pentose Phosphate Pathway
What are the 2 stages of FA synth and what is the (important) committed step?
Stage 1: Acetyl CoA (via Acetyl CoA Carboxylase) > Malonyl CoA
(this is the committed step)
Stage 2: Elongation (2C increments)
What is the committed step for FA biosynth?
What prosthetic group and other ingredient is required for this step?
Acytel CoA Carboxylase rxn
Biotin (Vita B7) and bicarbonate
What does Acetyl CoA carboxylase do to Acetyl CoA?
What does it yield?
Adds a Caboxyl group
(with biotin/B7 prosthetic group and at the expense of 1 ATP)
FA synth requires a carboxylation using CO2 then a decarboxylation
What allosterically regulates Acetyl CoA carboxylase?
Citrate (turns on)
Palmitoyl CoA (turns off)
What hormonally regulates Acetyl CoA carboxylase?
Insulin (via protein phophatase) turns on
Glucagon (via cAMP dependent protein kinase) turns off
What dephosphorylates (and activates) Acetyl CoA carboxylase?
What causes the protomers of Acetyl CoA carboxylase to polymerize?
What allosterically inhibits this process?
Citrate or Isocitrate
Malonyl CoA and Palmitoyl CoA
What are the required inputs for the synthesis of Palmitate?
8 Acetyl CoA
14 NADHP (remember, this comes from the PPP)
What is the main factor controlling the rate of lipogenesis?
The amount of enzyme, which is controlled by nutritional state
When are rates of FA synth greatest and lowest?
High carb/low fat meal
starvation (or a high fat diet)
What enzyme controls FA elongation?
Where does this occur?
Fatty Acid elongase
Where does Fatty Acid desaturation occur?
What enzyme is used?
Fatty Acyl CoA desaturase
What is the direct building block (two carbon donor) to FA synth?
What is the common intermediate between Triacylglycerol and Phospholipids?
(this matters because the glycerol comes from TAG breakdown to make Glycerol-3-P > Phosphatidate)
Why are TAG's only made in adipose if glucose is available?
What is the molecule involved?
Unlike the liver, the source of glycerol comes from the glycolytic pathway
dihydroxyacetone phosphate (this generates glycerol-3-P)
How is pyruvate returned to the mitochondria in FA synth?
Pyruvate > Oxaloacetate + Acetyl CoA = Citrate
Citrate leaves mito
Citrate > Acetyl CoA + Oxaloacetate
Oxaloacetate > Malate and back through Mitochondria
Where does cholesterol synthesis occur?
Cytosol (all 4 phases)
Mostly in the Liver
What do 3 Acetyl CoA's come together to form in Cholesterol biosynthesis?
Where does the NADPH come from in this rxn?
What is the key regulatory enzyme in Cholesterol biosynthesis?
HMG CoA reductase
HMG CoA > Mevalonate (step 3)
1st 3 steps in Cholesterol biosynthesis:
Acetyl CoA + Acetyl CoA > Acetoacetyl CoA + Acetyl CoA > HMG CoA (NADPH>NADP+) > Mevalonate
What does Mevalonate form in phase II (with multiple steps) of Cholesterol synthesis?
Outline Phase 2 of cholesterol synthesis:
Mevalonate > 3 Phosphorylations/1 decarboxylation
What are the 2 types of Isoprenoids made in phase II of cholesterol synthesis?
Isopentenyl pyrophosphate (IPP)
Dimethylallyl pyrophosphate (DPP)
Where do all Carbon atoms in cholesterol originally come from?
Phase 3 cholesterol synthesis:
Isoprenoids condense to Squalene (30C)
How many Carbons are in cholesterol?
Outline phase 4 of cholesterol synthesis:
Squalene circularized to Lanosterol
Lanosterol > Cholesterol
What suppresses HMG CoA reductase?
LDL take-up by the liver
HMG CoA in the mitochondria is used for?
HMG CoA in the cytosol is used for?
mito - makes ketone bodies
cytosol - makes cholesterol
The main enzyme (and rate limiting step) in the cytosol is HMG CoA reductase.
What is the enzyme in the mitochondria that makes ketone bodies from HMG CoA?
HMG CoA Lyase
How does HMG CoA make ketone bodies in the mitochondria?
loses Acetyl CoA to form acetoacetate
acetoacetate > D-Beta hydroxybutarate
Name two polar derivatives of cholesterol.
Glycocholate and Taurocholate
What are the 4 main classes of steroids derived from cholesterol and what are their precursors?
cholesterol > pregnenolone > progestagens
What is the precursor to Vitamin D?
What is the intermediate from which TAG's or phospholipids are formed?
TAG synthesis pathway:
Glycerol-3-Phosphate > lysophosphatidic acid > phosphatidate > DAG > TAG
Phosphatidate + CTP >
CDP - diacylglycerol
What eicosanoid is derived from omega-6?
What are the key eicosanoid enzymes?
omega 6 and 3's are both MUFA's that act as paracrine and autocrine messenger molecules.
What is the key enzyme in the production of prostaglandin?