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Flashcards in Metabolism 2 - Part 1 Deck (159):
1

What is the term for esterified fatty acids?

Triacylglycerol

2

Name 7 classes of lipids

Sphingolipids
Glycolipids
Glyceropholspholipids
Steroids
Triacylglycerol
Fatty Acids
Vitamins (ADEK)

3

Name a 2nd messenger lipid

DAG

diacylglycerol

4

Chains on the hydrocarbon part of fatty acids vary from ____ to ____ in length.

4-36

5

T/F
A fatty acid is nonpolar

False

carboxyl end is an acid

6

A molecule (like a fatty acid) that has both hydrophilic and hydrophobic characteristics is...

Amphipathic

7

What is the most common Fatty Acid in the body?
How many carbons?
saturation?

Palmitate
16
saturated

8

Describe the 2 notations counting carbon saturation in fatty acids

From COOH = delta (superscript)

From omega = n-6, etc

9

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

10

Palmitate is ______
Pamitoleic is ______

Saturated
Unsaturated

11

Mammalian enzymes cannot make a double bond more than ____ carbons away from the carboxylic end.

9

12

What is the name of an essential fatty acid required in diet
(comes in omega 3 and 6 forms)

Linoleic acid

13

Why do omega 3 and omega 6 pathways compete with each other?

They share the same enzymes

14

What do essential fatty acids like linoleic acid serve as a precursor for?

Eicosonoids

(prostaglandins)

15

What effects do eicosonoids have on the cell?
What is an example (precursor linoleic acid)

hormone-like

Arachidonic acid

16

What is the difference between a simple and a mixed triacylglycerol?

simple - has same carbon chains
mixed - has different (saturation levels/length) chains

17

What molecule is at the crossroads between making triacylglycerols and phospholipids?

Phosphatidate

(phosphatidic acid)

18

Why are triacylglycerols such a good form of energy storage?

Reduced and Anhydrous

19

16:0

Palmitic Acid

20

Name 5 things fatty acids are precursors to?

Glycolipids
Phospholipids
Sphingolipids
Prostaglandins
Cholesteryl esters

21

Short, medium, and long Fatty Acid lengths:

Short - 2-5 C's

Medium - 6-12 C's

Long- 12+

22

Short and unsaturated Fatty Acids tend to be:

Long and saturated Fatty Acids tend to be:

oils

solids

23

PUFA and MUFA tend to be oils. What do they stand for?

Polyunsaturated fatty acids
monounsaturated fatty acids

24

Where are trans fats made?
Why bad?

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

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