Ch. 11: Lipid and Amino Acid Metabolism Flashcards
(143 cards)
1
Q
what is dietary fat composed of? (5 + denote which is the main)
A
- triacyglycerols (main component)
- cholesterol
- cholesteryl esters
- phospholipids
- free fatty acids
2
Q
is there lipid digestion in the mouth and stomach?
A
it is very minimal, lipids are transported to the small intestine essentially intact
3
Q
what happens to lipids upon entry into the duodenum?
A
emulsification occurs, which is the mixing of the two normally immiscible liquids (in this case, fat and water)
4
Q
what advantage does formation of an emulsion have?
A
it increases the surface area of the lipid, permitting greater enzymatic interaction and processing
5
Q
what is emulsification aided by?
A
bile
6
Q
what 3 things is bile made of
A
- bile salts
- pigments
- cholesterol
7
Q
what is bile secreted by
what is bile stored by
A
secreted by: the liver
stored by: the gall bladder
8
Q
what 3 enzymes does the pancreas secrete into what
A
- pancreatic lipase
- colipase
- cholesterol esterase
into the small intestine
9
Q
what do the 3 pancreatic enzymes do together?
A
they hydrolyze the lipid components to 2-monnoacylglycerol, free fatty acids, and choleserol
10
Q
diagram: absorption of lipids
A
11
Q
what is emulsification followed by?
A
absorption of fats by intestinal cells
12
Q
what 4 items contribute to the formation of micelles?
A
- free fatty acids
- cholesterol
- 2-monoacylglycerol
- bile salts
13
Q
defn: micelles
A
clusters of amphipathic lipids that are soluble in the aqueous environment of the intestinal lumen
essentially: water-soluble spheres with a lipid-soluble interior
14
Q
func: micelles
A
vital in digestion, transport, and absorption of lipid-soluble substances starting from the duodenum all the way to the end of the ileum
15
Q
what happens at the end of the ileum? (2)
A
- bile salts are actively reabsorbed and recycled
- any fat that remains in the intestine will pass into the colon, and ultimately ends up in the stool
16
Q
where do micelles diffuse to? what happens after this?
A
the brush border of the intestinal mucosal cells where they are absorbed
after: the digested lipids pass through the brush border, where they are absorbed into the mucosa and re-esterified to form triacylglcyerols and cholesteryl esters and pakcaged, along with certain apoproteins, fat-soluble vitamins, and other lipids, into chylomcirons
17
Q
how do chylomicrons leave the intesine?
A
via lacteals, the vessels of the lymphatic system
18
Q
how do chylomicrons re-enter the bloodstream?
A
via the thoracic duct, a long lymphatic vessel that empties into the left subclavian vein at the base of the neck
19
Q
defn + time of day for the body: postabsorptive state
A
at night
utilizing energy stores (fatty acids released from adipose tissue) instead of food for fuel
20
Q
does human adipose tissue respond to glucagon or insulin?
A
human adipose tissue does NOT respond directly to GLUCAGON
but a fall in INSULIN levels activates a hormone-sensitive lipase (HSL) that hydrolyzes triacylglycerols, yielding fatty acids, and glycerol
21
Q
what 2 other hormones can also activate HSL?
A
- epinephrine
- cortisol
22
Q
what are the 2 reasons for which released glycerol from fat may be transported to the liver?
A
- glycolysis
- gluconeogenesis
23
Q
what is necessary for the metabolism of chylomicrons and very-low-density lipoproteins (VLDL)?
A
lipoprotein lipase (LPL)
24
Q
defn: lipoprotein lipase (LPL)
A
an enzyme that can release free fatty acids from triacylgycerols in these lipoproteins
25
diagram: metabolism of triacylglycerols and metabolism of the liver
26
free fatty acids are transported through the blood in association with what?
albumin, a carrier protein
27
how are triacylglycerol and cholesterol transported in the blood?
as lipoproteins
28
defn: lipoproteins
aggregates of apolipoproteins and lipids
29
what are lipoproteins named according to?
their density, which increases in direct proportion to the percentage of protein in the particle
30
density: chylomicrons
the least dense
highest fat to protein ratio
31
what is the order of density of lipoproteins from least to most?
1. chylomicrons
2. VLDL (ver-low-density lipoprotein)
3. IDL (intermediate-density)
4. LDL (low-density)
5. HDL (high-density)
32
what do chylomicrons and VLDL transport? main + secondary
main: triacylglycerols
secondary: cholesteryl esters
33
what do LDL and HDL transport?
primarily cholesterol
34
diagram: lipoprotein structure
35
table: classes of lipoproteins
36
char + func: chylomicrons
where does assembly of chylomicrons occur? what does this result in?
char: 1. highly soluble in lymphatic fluid and blood
func: function in the transport of dietary triacylgycerols, cholesterol, and cholesteryl esters to other tissues
assembly of chylomicrons occurs in the intestinal lining
results in: a nascent chylomicron that contains lipids and apolipoproteins
37
char (2) + func: VLDL (very-low-density lipoprotein)
where is VLDL produced and assembled?
char: 1. metabolism similar to that of chylomicrons
2. contain fatty acids that are synthesized from excess glucose or retrieved from chylomicron remnants
38
what is the resulting particle when triacylglcyerol is removed from VLDL? (2 names)
either a VLDL remnant or IDL (intermediate-density lipoprotein)
39
where is IDL reabsorbed/by what? (2)
func: IDL (intermediate-density lipoprotein)
IDL is reabsorbed 1. by apolipoproteins on the outside of the the liver and 2. further processed in the bloodstream
IDL func: 1. a transition particle between triacylgycerol transport (associated with chylomicrons and VLDL) and cholesterol transport (associated with LDL and HDL)
40
diagram: lipid transport in lipoproteins
TGL = triacylglycerol
CE = cholesteryl esters
chol = cholesterol
41
is the majority of cholesterol measured in blood associated with LDL or HDL?
LDL
42
func: LDL
main: 1. deliver cholesterol to tissues for biosynthesis
secondary: 1. important role in cell membranes
2. bile acids and salts are made from cholesterol in the liver
3. many other tissues require cholesterol for steroid hormone synthesis (steroidogenesis)
43
is HDL or LDL "good" cholesterol? why?
HDL is "good" because it picks up excess cholesterol from blood vessels for excretion
44
where is HDL synthesized? how is it released?
func (2)
synthesized in: the liver and intestines
released as: dense, protein-rich particles into the blood
func: 1. contains apolipoproteins used for cholesterol recovery (the cleaning up of excess cholesterol from blood vessels for excretion)
2.. delivers some cholesterol to steroidogenic tissues and transfers necessary apolipoproteins to some of the other lipoproteins
45
aka + defn: apolipoproteins
aka: apoproteins
form the protein component of the lipoproteins described above; receptor molecules, involved in signaling
46
func: apoA-I (specific apolipoprotein)
activates LCAT, an enzyme that catalyzes cholesterol esterification
47
func: apoB-48 (specific apolipoprotein)
mediates chylomicron secretion
48
func: apoB-100 (specific apolipoprotein)
permits update of LDL by the liver
49
func: apoC-II (specific apolipoprotein)
activates lipoprotein lipase
50
func: apoE (specific apolipoprotein)
permits uptake of chylomicron remnants and VLDL by the liver
51
defn: cholesterol
what 4 things does cholesterol play a major role in the synthesis of?
defn: a ubiquitous component of all cells in the human body
role in synthesis of: 1. cell membranes
2. steroid hormones
3. bile acids
4. vitamin D
52
Where does de novo synthesis of cholesterol occur
what is it driven by (2)
occurs in the liver
is driven by: acetyl-CoA and ATP
53
how does de novo synthesis of cholesterol occur? (4)
1. the citrate shuttle carries mitochondrial acetyl-CoA into the cytoplasm, where synthesis occurs
2. NADPH (from the pentose phosphate pathway) supplies reducing equivalents
3. synthesis of mevalonic acid in the smooth ER is the rate-limiting step in cholesterol biosynthesis and is catalyzed by 3-hydroxy-3-methylglutaryl (HMG) CoA reductase
54
what 3 ways is cholesterol synthesis regulated?
1. increased levels of cholesterol can inhibit further synthesis by a feedback inhibition mechanism
2. insulin promotes cholesterol synthesis
3. dependent on regulation of HMG-CoA reductase gene expression in the cell
55
what are the 2 specialized enzymes involved in cholesterol transport?
1. LCAT
2. CETP
56
defn + func: LCAT (lechithin-cholesterol acyltrnasferase)
an enzyme found in the bloodstream that is activated by HDL apoproteins
func: adds a fatty acid to cholesterol, which produces soluble cholesteryl esters such as those in HDL
57
func: CETP (cholesteryl ester transfer protein)
facilitates the transfer process of HDL cholesteryl esters can be distributed to other lipoproteins like IDL (which becomes LDL by acquiring these cholesteryl esters)
58
structure (3): fatty acids
1. long-chain carboxylic acids
2. C1 = carboxyl C
3. C2 = alpha C
59
how do fatty acids found within the body occur?
as salts that are capable of forming micelles or are esterified to other compounds
60
what 2 main characteristics are provided when describing a fatty acid and how are they written?
what can further description be given by?
1. the total number of C's
2. the number of double bonds
written as carbons:double bonds
further description can be given by indicating the position and isomerism of the double bonds in an unsaturated fatty acid
61
saturated vs. unsaturated fatty acids: double bonds
saturated: no double bonds
unsaturated: have one or more double bonds
62
what are two important essential fatty acids and what is their function?
1. alpha-linolenic acid
2. linoleic acid
these polyunsaturated fatty acids, as well as other acids formed from them, are important in maintaining cell membrane fluidity, which is critical for proper functioning of the cell
63
where do most unsaturated fatty acids come from for humans since they can only synthesize a few?
most come from essential fatty acids found in the diet that are transported in chylomicrons as triacylglycerols from the intestine
64
process + func: omega (w) numbering system
used for unsaturated fatty acids
the w designation describes the position of the last double bond relative to the end of the chain and identifies the major precursor fatty acid
65
are double bonds in natural fatty acids generally in the cis or trans configuration?
cis
66
true or false: excess carbohydrate and protein acquired from the diet can be converted to fatty acids and stored as energy reserves in the form of triacylglycerols
true
67
defn: nontemplate synthesi
lipid and carbohydrate synthesis
called this because they do not rely directly on the coding of a nucleic acid, unlike protein and nucleic acid synthesis
68
where does fatty acid biosynthesis occur? where do its products go?
occurs in the liver
its products are subsequently transported to adipose tissue for storage
69
what other body structure can synthesize smaller quantities of fatty acids?
adipose tissue
70
what are the 2 major enzymes of fatty acid synthesis and what are they stimulated by?
1. acetyl-CoA carboxylase
2. fatty acid synthase
stimulated by insulin
71
what is the primary end product of fatty acid synthesis?
palmitic acid (palmitate)
72
diagram: fatty acid synthesis from glucose
73
what happens to acetyl-CoA following a large meal?
it accumulates in the mitochondrial matrix and needs to be moved to the cytosol for fatty acid biosynthesis
74
what is acetyl-CoA the product of?
what does it couple with to form what in what cycle?
product of: pyruvate dehydrogenase complex
couples with oxaloacetate to form citrate at the beginning of the citric acid cycle
75
what is the rate-limiting enzyme of the TCA cycle and what is its effect?
isocitrate dehydrogenase
as the cell becomes energetically satisfied, it slows the TCA cycle and causes citrate accumulation
citrate can then diffuse across the mitochondrial membrane
76
what happens to citrate in the cytosol?
citrate lyase splits it back into acetyl-CoA and oxaloacetate (which can then return to the mitochondrion to continue moving acetyl-CoA)
77
for what and BY what is acetyl-CoA activated in the cytoplasm?
FOR: incorporation into fatty acids BY: acetyl-CoA carboxylase (the rate-limiting enzyme of fatty acid biosynthesis)
78
what 2 things does acetyl-CoA carboxylase require? + func of acetyl-CoA carboxylase
what is it activated by? (2)
requires: 1. biotin
2. ATP
func: adds CO2 to acetyl-CoA to form malonyl-CoA
activated by: 1. insulin and 2. citrate
79
why is the CO2 added to acetyl-CoA added to form malonyl-CoA never actually incorporated into the fatty acid?
because it is removed by fatty acid synthase during addition of the activated acetyl group to the fatty acid
80
why is fatty acid synthase more appropriately called palmitate synthase
because palmitate is the only fatty acid that humans can synthesize de novo
81
defn: fatty acid synthase
a large multienzyme complex found in the cytosol that is rapidly induced in the liver following a meal high in carbohydrates because of elevated insulin levels
82
what 3 does fatty acid synthase require and why? + what is one thing it contains?
contains: an acyl carrier protein (ACP)
requires: 1. pantothenic acid (vitamin B5) --> required by the ACP
2. NADPH (to reduce the acetyl groups added to the fatty acid)
3. 8 acetyl-CoA groups (to produce palmitate)
83
how may fatty acyl-CoA be elongated and desaturated to a limited extent?
using enzymes associated with the smooth ER
84
diagram + steps (6): fatty acid biosynthesis
1. acyl carrier protein
2. bond formation between activated malonyl-CoA (malonyl-ACP) and the growing chain (activation of the growing chain and malonyl-CoA with ACP and bond formation between these activated molecules)
3. reduction of a carbonyl group (to a hydroxyl group)
4. dehydration
5. reduction of a double bond (to a saturated fatty acid)
6. these reactions occur over and over again until the 16C palmitate molecule is created
85
what is the relationship between fatty acid biosynthesis and beta-oxidation?
they are reverse processes
both involve transport across the mitochondrial membrane, followed by a series of redox reactions, but always in the opposite direction of one another
86
how are triacylglycerols formed? where does this occur? + func
func: storage form of fatty acids
formed by: attaching 3 fatty acids (as fatty acyl-CoA) to glycerol
occurs: primarily in the liver, and somewhat in adipose tissue, with a small bit from diet
87
what happens to triacylglycerols in the liver?
they are packaged and sent to adipose tissue as very-low-density lipoproteins (VLDL), leaving only a small amount of stored triacylglycerols
88
how does most fatty acid catabolism proceed?
via beta-oxidation that occurs in the mitochondria
there is also peroxisomal beta-oxidation
89
what are alpha-oxidation and omega-oxidation?
alpha-oxidation: branched-chain fatty acids may undergo this, depend on the branch points
omega-oxidation in the ER produces dicarboxylic acids
90
what inhibits and what stimulates beta-oxidation?
insulin inhibits
glucagon stimulates
91
what happens when fatty acids are metabolized? what is the product?
what happens? they first become activated by attachment to CoA (which is catalyzed by fatty-acyl-CoA synthetase)
the product? generally referred to as fatty acyl-CoA or acyl-CoA
92
what are 2 examples of products of fatty acid metabolism?
acetyl-CoA (contains a 2C acyl group)
palmitoyl-CoA (contains a 16C acyl group)
93
how do short-chain, medium-chain, and long-chain fatty acids enter into the mitochondria? what length of C's are each of these?
SHORT-chain fatty acids = 2-4 C's
MEDIUM-chain fatty acids = 6-12C's
SHORT and MEDIUM diffuse freely into mitochondria, where they are oxidized
LONG-chain fatty acids = 14-20 C's
LONG are oxidized in the mitochondria and require transport via a carnitine shuttle
94
what is the rate-limiting enzyme of fatty acid oxidation?
carnitine acyltransferse I
95
how long are and where are very long chain fatty acids oxidized?
over 20 C's
oxidized elsewhere in the cell
96
diagram: fatty acid activation and transport
97
summary func: beta-oxidation
reverses the process of fatty acid synthesis by oxidizing and releasing (rather than reducing and linking) molecules of acetyl-CoA
98
beta-oxidation is a repetition of four steps, what happens in sum with each four-step cycle?
one acetyl-CoA is released and NAD+ and FAD are reduced (producing NADH and FADH2)
99
what happens to the FADH2 and NADH that are produced by beta-oxidation?
they are oxidized in the electron transport chain, producing ATP
100
what happens to the acetyl-CoA produced by beta-oxidation?
in muscle and adipose tissue: it enters the TCA cycle
in the liver: cannot be converted to glucose and so stimulates gluconeogenesis by activating pyruvate carboxylase
101
what changes about the production of acetyl-CoA from the liver in a fasting state?
the liver produces more acetyl-CoA from Beta-oxidation than is used in the TCA cycle
102
what does much of the acetyl-CoA from beta-oxidation get used for?
to synthesize ketone bodies (essentially 2 acetyl-CoA molecules linked together) that are released into the bloodstream and transported to other tissues
103
diagram + words: the 4 steps of beta-oxidation
1. Oxidation of the fatty acid to form a double bond
2. Hydration of the double bond to form a hydroxyl group
3. Oxidation of the hydroxyl group to form a carbonyl (Beta-ketoacid)
4. Splitting of the beta-ketoacid into a shorter acyl-CoA and acetyl-CoA
104
when does beta-oxidation stop?
when the chain has been shortened by 2 C's, creating a final acetyl-CoA
105
do fatty acids with an odd number of C's undergo beta-oxidation in the same manner as even-numbered C fatty acids?
for the most part
the only difference is observed during the final cycle: even-numbered fatty acids yield 2 acetyl-CoA molecules (from the 4C remaining fragment)
odd-numbered fatty acids yield one acetyl-CoA and one propionyl-CoA (from the 5C remaining fragment)
106
what happens to propionyl-CoA?
it is converted to methylmalonyl-CoA by propionyl-CoA carboxylase which requires biotin (vitamin B7)
107
what happens to methylmalonyl-CoA?
it is converted into succinyl-CoA by methylmalonyl-CoA mutase, which requires cobalamin (vitamin B12)
108
what happens to succinyl-CoA?
it is a TCA cycle intermediate and can also be converted to malate to enter the gluconeogenic pathway in the cytosol
109
what do odd-C fatty acids represent?
an exception to the rule that fatty acids cannot be converted to glucose in humans
110
diagram: propionic acid pathway
111
why are 2 additional enzymes necessary for oxidation of unsaturated fatty acids?
because double bonds can disturb the stereochemistry needed for oxidative enzymes to act on the fatty acid
112
what must be true for the 2 additional enzymes for the oxidation of unsaturated fatty acids to function?
they can have at most one double bond in their active site and this bond must be located between C's 2 and 3?
113
func + diagram: enoyl-CoA isomerase
rearranges cis double bonds at the 3,4 position to trans double bonds at the 2,3 position once enough acetyl-CoA has been liberated to isolate the double bond within the first 3 C's
114
what effect does the step accomplished by enoyl-CoA isomerase accomplish with monounsaturated fatty acids?
permits beta-oxidation to proceed
115
what is required for polyunsaturated fatty acids? + diagram
a further reduction required using 2,4-dienoyl-CoA reductase to convert 2 conjugated double bonds to just one double bond at the 3,4 position, where it will then undergo the same rearrangement as monounsaturated fatty acids to form a trans 2,3 double bond
116
summary defn: ketone bodies
essentially are transportable forms of acetyl-CoA
117
what produces ketone bodies? what uses ketone bodies?
produced by: the liver
used by: other tissues during prolonged starvation
118
what does the liver do to excess acetyl-CoA when in the fasting state?
the liver converts acetyl-CoA from beta-oxidation of fatty acids into the ketone bodies acetoacetate and 3-hydroxybutyrate (beta-hydroxybutyrate)
119
what can cardiac, skeletal muscle and the renal cortex do to acetoacetate and 3-hydroxybutyrate?
metabolize them to acetyl-CoA
120
what is the relationship between how muscles act during fasting periods and how the liver acts during fasting periods?
muscle will metabolize ketones as rapidly as the liver releases them, preventing accumulation in the bloodstream
121
what happens to ketones after a week of fasting?
they reach a concentration in the blood that is high enough for the brain to begin metabolizing them
122
diagram: ketogenesis and ketolysis
123
what leads to ketoacidosis and when does this most often happen?
a significant increase in ketone levels in the blood can lead to this
most often occurs with fatty acid breakdown in type 1 (insulin-dependent) diabetes mellitus
124
when and where does ketogenesis occur? + what reactions occur (3)
in the mitochondria of liver cells when excess acetyl-CoA accumulates in the fasting state
1. HMG-CoA synthase forms HMG-CoA
2. HMG-CoA lyase breaks down HMG-CoA into acetoacetate, which can subsequently be reduced to 3-hydorxybutyrate
3. acetone is a minor side product that is formed but will not be used as energy for tissues
125
what reactions happen during ketolysis? (2)
1. acetoacetate picked up from the blood is activated in the mitochondria by succinyl-CoA acetoacetyl-CoA transferase (aka thiophorase), an enzyme present only in tissues outside the liver
2. during that reaction, acetoacetate is oxidized to acetoacetyl-CoA
126
why can't the liver catabolize the ketone bodies that it produces?
it lacks the enzyme necessary (thiophorase)
127
what happens to the brain after a prolonged fast (longer than a week)? (4)
1. the brain begins to derive up to 2/3 of its energy from ketone bodies
2. when ketones are metabolized to acetyl-CoA in the brain, pyruvate dehydrogenase is inhibited
3. glycolysis and glucose uptake in the brain decreases
4. this spares essential protein in the body, which otherwise would be catabolized to form glucose by gluconeogenesis in the liver and allows the brain to indirectly metabolize fatty acids as ketone bodies
128
why is protein very rarely used as an energy source?
because it is so important for other functions and digestion of protein compromises muscle
129
in what context can proteins be used for energy?
under conditions of extreme energy deprivation
130
why must proteins be digested and absorbed?
in order to provide a reservoir of amino acids for protein building by the cell
131
what is metabolism directed toward?
conserving tissues to the greatest extent possible, especially the brain and heart
132
defn: proteolysis
the breakdown of proteins/protein digestion
133
process (4): proteolysis
1. begins in the stomach with pepsin
2. continues with the pancreatic proteases trypsin, chymotrypsin, and carboxypeptidases A and B (all of which are secreted as zymogens)
3. completed by the small intestinal brush-border enzymes dipeptidase and aminopeptidase
4. the main end products are amino acids, dipeptides, and tripeptides
134
how are amino acids and small peptides absorbed?
through the luminal membrane by secondary active transport linked to sodium
135
how are amino acids transported into the bloodstream?
by simple and facilitated diffusion at the basal membrane
136
diagram: absorption of amino acids and peptides in the intestine
137
where is body protein primarily catabolized?
in muscle and the liver
138
how do amino acids released from proteins usually lose their amino group? what happens after?
through transamination or deamination
after: the remaining carbon skeleton can be used for energy
139
defn (sum + each + which): glucogenic vs. ketogenic amino acids
classification by their ability to turn into specific metabolic intermediates
glucogenic (all but leucine and lysine) can be converted into glucose through gluconeogenesis
ketogenic (leucine, lysine, isoleucine, phenylalanine, threonine, tryptophan, and tyrosine) can be converted into acetyl-CoA and ketone bodies
140
what is true about the amino groups removed by transamination or deamination?
they are a potential toxin to the body in the form of ammonia, and must be excreted safely
141
location + func: urea cycle
occurs in the liver
the body's primary way of removing excess nitrogen from the body
142
diagram: urea cycle
143
what happens to the side chain of each amino acid during proteolysis?
it depends on its chemistry
BASIC: amino acid side chains feed into the urea cycle
OTHER: amino acid side chains act like the carbon skeleton and produce energy through gluconeogenesis or ketone production
