Metabolism 2 - Part 1 Flashcards
1
Q
What is the term for esterified fatty acids?
A
Triacylglycerol
2
Q
Name 7 classes of lipids
A
Sphingolipids Glycolipids Glyceropholspholipids Steroids Triacylglycerol Fatty Acids Vitamins (ADEK)
3
Q
Name a 2nd messenger lipid
A
DAG
diacylglycerol
4
Q
Chains on the hydrocarbon part of fatty acids vary from ____ to ____ in length.
A
4-36
5
Q
T/F
A fatty acid is nonpolar
A
False
carboxyl end is an acid
6
Q
A molecule (like a fatty acid) that has both hydrophilic and hydrophobic characteristics is…
A
Amphipathic
7
Q
What is the most common Fatty Acid in the body?
How many carbons?
saturation?
A
Palmitate
16
saturated
8
Q
Describe the 2 notations counting carbon saturation in fatty acids
A
From COOH = delta (superscript)
From omega = n-6, etc
9
Q
Where are the alpha, beta, and omega carbons in a FA chain?
A
alpha - one away from C1 (the carboxylic Carbon)
beta - two away from C1
omega - the last C
10
Q
Palmitate is ______
Pamitoleic is ______
A
Saturated
Unsaturated
11
Q
Mammalian enzymes cannot make a double bond more than ____ carbons away from the carboxylic end.
A
9
12
Q
What is the name of an essential fatty acid required in diet
comes in omega 3 and 6 forms
A
Linoleic acid
13
Q
Why do omega 3 and omega 6 pathways compete with each other?
A
They share the same enzymes
14
Q
What do essential fatty acids like linoleic acid serve as a precursor for?
A
Eicosonoids
prostaglandins
15
Q
What effects do eicosonoids have on the cell?
What is an example (precursor linoleic acid)
A
hormone-like
Arachidonic acid
16
Q
What is the difference between a simple and a mixed triacylglycerol?
A
simple - has same carbon chains
mixed - has different (saturation levels/length) chains
17
Q
What molecule is at the crossroads between making triacylglycerols and phospholipids?
A
Phosphatidate
phosphatidic acid
18
Q
Why are triacylglycerols such a good form of energy storage?
A
Reduced and Anhydrous
19
Q
16:0
A
Palmitic Acid
20
Q
Name 5 things fatty acids are precursors to?
A
Glycolipids Phospholipids Sphingolipids Prostaglandins Cholesteryl esters
21
Q
Short, medium, and long Fatty Acid lengths:
A
Short - 2-5 C’s
Medium - 6-12 C’s
Long- 12+
22
Q
Short and unsaturated Fatty Acids tend to be:
Long and saturated Fatty Acids tend to be:
A
oils
solids
23
Q
PUFA and MUFA tend to be oils. What do they stand for?
A
Polyunsaturated fatty acids
monounsaturated fatty acids
24
Q
Where are trans fats made?
Why bad?
A
industrial hydrogenation processes
body lacks enzymes to break down
(only breaks cis)
25
What is the major intermediate found both in triacylglycerides and phospholipids?
Phosphatidic acid
26
What are 2 essential fatty acids?
Linoleic and alpha linoleic acid
| remember - precursor to eicosonoids
27
Arachidonic acid is synthesized entirely by what fatty acid?
Linoleic Omega 6 form
28
What two things distinguish apple (as opposed to pear) shape?
Metabolically active and dangerous
29
Where does lipid digestion begin?
in mouth (Lingual Lipase)
but this process isn't efficient in adults
30
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)
31
What converts macroscopic fat cells into micelles?
Bile salts
32
What are bile acids made from and what are they secreted as?
cholesterol derivatives
secreted as taurine and glycine salts
33
Name the 3 bile acids
Cholic
Glycocholic
Taurocholic
34
What is the process of bile acid reabsorption to the liver via the portal vein called?
Enterohepatic Cycle
35
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
36
What is the small peptide hormone released by the jejunum in response to chyme?
Cholecystokinin
37
What are 3 functions of Cholecystokinin?
Stimulates gall bladder release
Releases pancreatic enzymes
Slows digestion from stomach (gastric emptying)
38
What is released into the duodenum in response to low pH of chyme?
What does it induce?
Secretin
induces pancreas to release bicarbonate (buffer)
39
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)
Cholesterol esterase
Phospholipase A2
40
What stabilizes the lipid-water interface interactions (surface area of which digestion depends) of Pancreatic Lipase?
Colipase
| also secreted by pancreas
41
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?
Ala-Pro-Gly-Pro-Arg
| damn near palindromic
42
What substrate and enzyme create cholesterol in the intestine?
Cholesteryl ester + Cholesteryl esterase (hydrolyzes)
= Cholesterol + Fatty acid
43
The proenzyme of Phospholipase A2 is activated by...
Trypsin
44
```
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
45
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?
FABP2/I-FABP
46
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)
47
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
Serum Albumin
48
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
49
CE
PL
substrate>enzyme>products
Cholesteryl ester > cholesteryl esterase > cholesterol
Phophatidylcholine > Lipase > glycerylphosphorylcholine
50
TAG
| substrate>enzyme>product
Triacylglycerol > pancreatic lipase > 2-monoacylglycerol
51
What is lingual lipase's target?
Phophatidylcholine (PL)
52
Why is Gastric lipase useful if its optimal pH is around 7?
It's only really used in babies.
53
What does pancreatic lipase break a TAG into?
2 Fatty Acids
| 1 Monoglyceride
54
What peptide hormone is responsible for stimulating the digestion of fat and protein?
(also acts as a hunger suppressant)
CCK
| cholecystokinin
55
What does FACS stand for?
| trapping mechanism
Fatty Acyl CoA Synthetase
remember: works on both FA>TAG and sterol>steryl
56
What is found in a chylomicron?
| What is found on a chylomicron?
Triglycerides (mostly)
Apo B48, phospholipid, free cholesterol, ApoA
57
What hydrolyzes chylomicrons?
Lipoprotein Lipase (LPL)
58
Where are FFA's, monoacylglycerides, and cholesterol found?
Where are TAG's, cholesteryl ester, glycerylphophorylcholine found?
Intestinal lumen
mucosal intestinal cells
59
Trace chylomicron to blood
Intestinal mucosal cells > lymph > Subclavian vein via thoracic duct > superior vena cava
60
List the lipoproteins from biggest to smallest
```
Chylomicron
VLDL
LDL
IDL
HDL
```
61
What is the major difference between a chylomicron and VLDL?
Chylomicron carries dietary fat
VLDL carries synthesized fat
62
What does the shell of a chylomicron contain?
Apolipoproteins
| Apo B48 and Apo A
63
What is a known marker for Alzheimers?
allele marker for ApoE
64
What docks to lipoprotein lipase in the capillary?
Apo CII
65
Where do Chylomicrons pick up ApoCII and ApoE?
HDL
66
After ApoCII activates lipoprotein lipase, where do TAG's generally go?
Where does glycerol go?
Heart, muscle, adipose tissue
Liver
67
How is the chylomicron remnant taken up by the liver?
ApoE receptors
68
Fatty Acid + CoA + ATP >
| this is the rxn allowing cell to hold on to FA
Acyl CoA + AMP + PPi
69
In the liver, what are excess fats (and indirectly carbs) packaged into?
VLDL
70
Name 5 apolipoproteins in VLDL.
```
ApoB-100
ApoC-I
ApoC-II
ApoC-III
ApoE
```
71
What lipoprotein do nascent VLDL have on their surface?
ApoB-100
72
Where does VLDL pick ApoC-II and ApoE?
remember: ApoC-II interacts with lipoprotein lipase to release FA's from TAGs into cells)
HDL
73
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
Cholesterol
74
What is the primary function of LDL?
Delivery of Cholesterol
75
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
76
What 2 apolipoproteins does HDL provide (act as a reservoir) for chylomicrons and VLDL?
ApoC-II and ApoE
77
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
78
What exchanges choleteryl ester from HDL for TAG from VLDL?
Cholesteryl ester transferase protein (CETP)
79
Apolipoproteins on a:
Nascent chylomicron
"mature"
"spent"
ApoB48
ApoB48, ApoCII, ApoE (latter 2 from HDL)
ApoB48, ApoE (latter gets into liver, ApoCII taken back by HDL)
80
What is the adipose, heart , muscle, live distribution of chylomicrons?
80% - adipose, heart, muscle
| 20% - liver
81
Apolipoproteins associated with:
chylomicron
VLDL
ApoB48 (and ApoCII, ApoE from HDL)
ApoB100 (and ApoCII, ApoE from HDL)
82
Which lipid is highest in cholesteryl esters?
| highes in protein/lipid ratio?
LDL
| HDL
83
What does HMG CoA reductase do and what downregulates its actions?
makes cholesterol in the liver
LDL binding liver downregulates
84
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
85
Where are the exceptions to fat being the dominant form of energy?
Brain and RBC's
86
When does ketogenesis take place?
When Acetyl CoA is high and Oxaloacetate is low
87
What makes and uses ketone bodies?
| not really ketones, but organic acids that drop pH
Liver makes but does NOT use.
Everything else uses.
88
What favors ketogenesis?
low insulin/glucagon ratio
| a lot of glucagon
89
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
90
What does PKA, from the Adenelyate Cyclase pathway, activate by phosphorylation?
Breakdown of TAG to DAG
| then other lipases break down further
91
What is the initial effector of the Adenelyate Cyclase pathway leading to TAG breakdown?
Hormone (glucagon and epinepherine)
This is a Hormone Sensitive Lipase
92
What is the fate of released glycerol in TAG breakdown?
Liver GNG or glycolysis
| both in liver
93
In the cell, where does building and breaking down fat occur?
Build - in cell
Break down - in mitochondria
94
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
95
What size Fatty Acids go through the Carnitine Cycle to enter the mitochondria?
Where do they go if they're bigger?
12-20
Peroxisome
96
What inhibits carnitine acyltransferase (CPT-1) from transfering Fatty acyl residues to acyl carnitine?
Malonyl CoA
| a substrate of fat synthesis
97
What is exchanged in a 1:1 ratio through a translocase at the IMM?
Fatty acyl carnitine for carnitine
98
Once in the Matrix, what is responsible for changing Fatty acyl carnitine back to Fatty acyl CoA
Carnitine Acyltransferase II (CPT-II)
99
What does Palmitate (16:0) yield upon Beta-Oxidation?
8 Acetyl CoA
7 NADH
7 FADH2
7 H+
100
What does each turn of Beta Oxidation yield?
1 Acetyl CoA
1 NADH
1 FADH2
(each pass takes off 2 Carbons)
101
What is the first step (most important) Enzyme in Beta-Oxidation?
acyl-CoA dehydrogenase
102
Where are very long chain FA catabolized?
Peroxisomes
103
What are the final products in Long Chain Fatty Acid Oxidation?
Are NADH and FADH2 produced in this process?
Octanoyl CoA
Acetyl CoA
(both metabolized in mitochondria)
no
104
What enzyme changes H2O2 to Water and oxygen in the peroxisome?
Catalase
105
What is the odd numbered Fatty acid of metabolism?
| What is its coenzyme?
Propionyl CoA
| B12 (biotin)
106
How are unsaturated fatty acids metabolized?
Isomerized, Oxidized, and miss the first redox rxn
107
What are unsaturated fatty acids isomerized to?
Trans (delta 2) Enoyl CoA
| then oxidized
108
What is the most important (for this class) ketone body?
D-3-Hydroxybutarate
109
What are the 3 ketone bodies?
| Where are they made?
Acetoacetate (this makes two products, which are)
Acetone
D-3-Hydroxybutarate
Made exclusively in the liver (these are basically mobile acetyl CoA)
110
What does uncontrolled ketone body formation lead to?
Ketoacidosis
111
What is the starting product of Ketogenesis and where does it occur?
2 Acetyl CoA's
Liver only
112
Where does Fatty Acid synthesis occur?
| organs and location in cell
Liver and lactating mammary glands
Cytosol
113
How many Acetyl Coa does it take to make Palmitate?
8
114
Where is the Acetyl CoA used in palmitate synthesis produced?
Where is it used?
Produced in the mitochondria
Used in the cytosol
115
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)
116
What pathway provides NADPH for FA synth?
Pentose Phosphate Pathway
117
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)
118
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
119
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)
Malonyl CoA
120
T/F
| FA synth requires a carboxylation using CO2 then a decarboxylation
True
121
What allosterically regulates Acetyl CoA carboxylase?
Citrate (turns on)
Palmitoyl CoA (turns off)
122
What hormonally regulates Acetyl CoA carboxylase?
Insulin (via protein phophatase) turns on
Glucagon (via cAMP dependent protein kinase) turns off
123
What dephosphorylates (and activates) Acetyl CoA carboxylase?
PP2A
124
What causes the protomers of Acetyl CoA carboxylase to polymerize?
What allosterically inhibits this process?
Citrate or Isocitrate
Malonyl CoA and Palmitoyl CoA
125
What are the required inputs for the synthesis of Palmitate?
8 Acetyl CoA
7 ATP
14 NADHP (remember, this comes from the PPP)
126
What is the main factor controlling the rate of lipogenesis?
The amount of enzyme, which is controlled by nutritional state
127
When are rates of FA synth greatest and lowest?
High carb/low fat meal
starvation (or a high fat diet)
128
What enzyme controls FA elongation?
| Where does this occur?
Fatty Acid elongase
ER
129
Where does Fatty Acid desaturation occur?
| What enzyme is used?
ER
Fatty Acyl CoA desaturase
130
What is the direct building block (two carbon donor) to FA synth?
Malonyl CoA
131
What is the common intermediate between Triacylglycerol and Phospholipids?
Phosphatidate
| this matters because the glycerol comes from TAG breakdown to make Glycerol-3-P > Phosphatidate
132
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)
133
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
134
Where does cholesterol synthesis occur?
Cytosol (all 4 phases)
Mostly in the Liver
135
What do 3 Acetyl CoA's come together to form in Cholesterol biosynthesis?
Where does the NADPH come from in this rxn?
Mevalonate (6C)
PPP
136
What is the key regulatory enzyme in Cholesterol biosynthesis?
What step?
HMG CoA reductase
HMG CoA > Mevalonate (step 3)
137
1st 3 steps in Cholesterol biosynthesis:
Acetyl CoA + Acetyl CoA > Acetoacetyl CoA + Acetyl CoA > HMG CoA (NADPH>NADP+) > Mevalonate
138
What does Mevalonate form in phase II (with multiple steps) of Cholesterol synthesis?
Isoprenoid
139
Outline Phase 2 of cholesterol synthesis:
Mevalonate > 3 Phosphorylations/1 decarboxylation
Isoprenoid
140
What are the 2 types of Isoprenoids made in phase II of cholesterol synthesis?
```
Isopentenyl pyrophosphate (IPP)
Dimethylallyl pyrophosphate (DPP)
```
141
Where do all Carbon atoms in cholesterol originally come from?
Acetyl CoA
142
Phase 3 cholesterol synthesis:
Isoprenoids condense to Squalene (30C)
143
How many Carbons are in cholesterol?
27
144
Outline phase 4 of cholesterol synthesis:
Squalene circularized to Lanosterol
Lanosterol > Cholesterol
145
What suppresses HMG CoA reductase?
LDL take-up by the liver
146
HMG CoA in the mitochondria is used for?
HMG CoA in the cytosol is used for?
mito - makes ketone bodies
cytosol - makes cholesterol
147
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
148
How does HMG CoA make ketone bodies in the mitochondria?
loses Acetyl CoA to form acetoacetate
| acetoacetate > D-Beta hydroxybutarate
and acetone
149
Name two polar derivatives of cholesterol.
Bile Salts
Glycocholate and Taurocholate
150
What are the 4 main classes of steroids derived from cholesterol and what are their precursors?
cholesterol > pregnenolone > progestagens
glucocorticoids
mineralocorticoids
androgens
estrogens
151
What is the precursor to Vitamin D?
cholesterol
152
What is the intermediate from which TAG's or phospholipids are formed?
Phosphatidate
| diacylglyceride
153
TAG synthesis pathway:
Glycerol-3-Phosphate > lysophosphatidic acid > phosphatidate > DAG > TAG
154
Phosphatidate + CTP >
CDP - diacylglycerol
155
What eicosanoid is derived from omega-6?
omega-3?
Arachidonic
Eicosapentanoic (EPA)
156
What are the key eicosanoid enzymes?
cyclooxengenase (COX)
| lipooxygenase (LOX)
157
T/F
| omega 6 and 3's are both MUFA's that act as paracrine and autocrine messenger molecules.
False
PUFA
158
What is the key enzyme in the production of prostaglandin?
COX
159
What is the key enzyme that makes thromboxane?
thromboxane A synthase
