Chapter 7 Flashcards
1
Q
Definition of metabolism.
A
all chemical reactions and pathways that occur in a living organism to maintain life
2
Q
What are the pathways that require energy called?
A
synthetic; anabolic
3
Q
What are the pathways that yield energy called?
A
degradative; catabolic
4
Q
What is the main purpose of catabolic reactions?
A
to break down macronutrients so their inherent energy can be released and transformed into ATP
5
Q
What is the main purpose of anabolic reactions?
A
synthesize complex molecules from simple precursors by utilizing the energy from ATP and, in some key reactions, GTP and UTP
6
Q
If cellular energy (ATP) is needed - the following processes will occur.
A
Pyruvate from glycolysis is sent to the mitochondria, decarboxylated to acetyl-CoA, and oxidized via the TCA cycle to produce ATP through oxidative phosphorylation.
7
Q
What is the processes of fatty acids being catabolized?
A
can be catabolized to acetyl-CoA in mitochondria, resulting in the production of ATP via the TCA cycle and oxidative phosphorylation
8
Q
What happens when carbohydrates and lipids are short in supply?
A
amino acids are converted to pyruvate and acetyl-CoA, thus providing needed energy for ATP production
9
Q
What are amino acids used to replenish?
A
many of the intermediates of the TCA cycle to ensure the cycle’s continued operation
10
Q
What can pyruvate and acetyl-CoA be used to produce?
A
more complex molecules when the cellular energy status favors anabolic reactions
11
Q
What is pyruvate convert too?
A
glucose via gluconeogenesis
12
Q
What is acetyl-CoA used for?
A
fatty acid synthesis
13
Q
What reaction is irreversible and why?
A
pyruvate to acetyl-CoA this prevents appreciable amounts of acetyl-CoA from being used for gluconeogenesis
14
Q
Why do we want to reduce the amount of acetyl-CoA used for gluconeogenesis?
A
because it’s a non-glucogenic molecule (meaning it cannot be directly converted back into glucose) and its excess can lead to the formation of ketone bodies (detrimental)
15
Q
How is acetyl-CoA produced?
A
during the breakdown of carbohydrates, fats, and proteins
16
Q
How are the TCA cycle intermediates replenished for anabolic reactions?
A
conversion of pyruvate to oxaloacetate
17
Q
example of TCA cycle intermediate enter AP: citrate
A
can move from the mitochondria into the cytosol, where citrate lyase cleaves it into oxaloacetate and acetyl-CoA, the latter being used for FAS
18
Q
example of TCA cycle intermediate enter AP: malate
A
the presence of NADP+ - linked malic enzyme, may provide a portion of the NADPH required for reduction reactions in FAS
19
Q
example of TCA cycle intermediate enter AP: succiyl-CoA
A
can combine with glycine in the mitochondria to form delta-aminolevulinic in the initial step in heme synthesis
20
Q
example of TCA cycle intermediate enter AP: oxaloacetate
A
may be used for conversion to amino acids or it may enter the gluconeogenesis pathway
21
Q
examples of TCA cycle intermediate enter AP: CO2
A
produced by the TCA cycle is a source of cellular carbon for carboxylation reactions that initiate fatty acid synthesis and gluconeogenesis. - this can also supply the carbon of urea and certain portions of the purine and pyrimidine rings
22
Q
what is required and a major electron donor in cells that drive anabolic reactions?
A
NADPH
23
Q
How is NADPH needed for anabolic reactions supplied?
A
by the pentose phosphate pathway, which also produces ribose-5-phosphate used in the synthesis of nucleotides
24
Q
What are example of regulatory enzymes?
A
glycogen synthase and phosphorylase
25
What molecules concentration declines as energy status of the cell declines?
acetyl-CoA, citrate and ATP due to decreased glycolysis, lipolysis (B-oxidation), and TCA cycle reactions
26
What do increased amount of ADP and AMP indicate?
that ATP has been used up in anabolic reactions and more ATP is needed
27
What does a decrease of concentration of malonyl-COA show?
little or no fatty acid synthesis occurring during low energy status
28
When cellular ATP is abundant what other molecules are also abundant?
ATP, acetyl-CoA and citrate
29
ATP, acetyl-CoA and citrate work to do what?
allosterically inhibit regulatory enzymes that govern glycolysis and the TCA cycle while stimulating gluconeogenesis and fatty acid synthesis as a way of capturing and storing the energy for later use
30
What is required for the transport of activated fatty acids (like fatty acyl-CoA) into the mitochondria for oxidation?
CAT 1
31
what does increased cellular concentration of malonyl-CoA block?
CAT 1 and prevent transport and subsequent oxidation
32
When can CAT I function?
in the absence of malonyl-CoA
33
What will occur if energy is not needed by the cell?
acetyl-CoA will be carboxylated to form malonyl-CoA (1st step of FAS)
34
When are malonyl-CoA at it's highest and lowest?
in the fed state and decline with fasting
35
What increases malonyl-CoA in skeletal muscle?
glucose and insulin - resulting in a decrease in B-oxidation of fatty acids due to the inactivation of AMPK
36
What occurs when energy status of the cell is low?
recruitment of fatty acids from the circulation increases the cytosolic fatty acyl-CoA concentration
37
Elevated malonyl-CoA levels in B-cells inhibit?
the transfer of fatty acids into the mitochondria and the increased fatty acid levels in the cytosol act as a coupling factor for insulin secretion
38
What does the activation of AMPK indicate?
low energy status of the cell
39
What are examples of low energy status?
fasting, increase ATP utilization that occurs with muscle contraction and metabolic stresses that interfere with ATP production such as hypoxia
40
What does AMPK activate?
a transporter protein in adipocytes and muscle cells involved in the translocation of GLUT4 to the plasma membrane, increasing the uptake of glucose into the cell
41
How does AMPK stimulate glycolysis and where?
mainly in cardiac muscle by phosphorylating phosphofructokinase-2, which produces 2,6-biphosphate, a potent allosteric activator of phosphofructokinase
42
What is the function of AMPK?
prevents cellular energy from being diverted into anabolic pathways by inhibiting glycogen synthase and the gluconeogenic enzyme phosphoenolpyruvate carboxykinase and glucose-6-phosphatase
43
What occurs when AMP:ATP ratio is high?
the promotion of fatty acid uptake into cardiac muscle increases the translocation of the fatty acid transporter CD36 of the plasma membrane
44
What does activated AMPK inhibit?
acyltransferases involved in triacylglycerol and phospholipid synthesis
45
Amino acids are only called upon for energy when?
carbohydrate and lipid are insufficient
46
What can most amino acids serve as precursors for?
glucose or fatty acid/triacylglycerol synthesis
47
what can carbohydrates be used to synthesize?f
fatty acids and triacylglycerols
48
What cannot be used to make glucose and why?
fatty acids and it's because humans lack the necessary enzymes to convert acetyl-CoA to pyruvate or any intermediate along the gluconeogenic pathway
49
When is most of the acetyl-CoA produced?
in the mitochondria through the B-oxidation of fatty acids
50
What happens when acetyl-CoA is involved in AR?
it has to be translocated back to the cytosol across the mitochondrial membrane (which is not permeable to it)
51
If acetyl-CoA cannot enter the mitochondrial membrane what occurs?
acetyl-CoA in the mitochondria combines with oxaloacetate to form citrate (as in the TCA cycle) - to which the mitochondrial membrane is freely permeable
52
first step of fatty acid synthesis (how acetyl-CoA enters mitochondria)
the acetyl-CoA may undergo a carboxylation reaction catalyzed by acetyl-CoA carboxylase to form malonyl-CoA
53
Where can the fatty acid components of triacylglycerols com from adipose tissue?
from the diet, via lipolysis, or from the liver (where they are synthesized and packaged for delivery to adipocytes by VLDL)
54
What does muscle and adipose tissue lack?
glycerol kinase that can phosphorylate glycerol directly and must obtain the glycerol-3 phosphate through glycolysis
55
Why is the conversion of fatty acids into carbohydrate no possible?
because the pyruvate dehydrogenase reaction is not reversible
56
Acetyl-CoA produce from any source must be used for?
ATP production, lipogenesis, cholesterol synthesis, or ketogenesis
57
What is the exclusive site for the formation of urea?
hepatocytes
58
What are hepatic fatty acids derived from?
chylomicron remnants and from de novo synthesis
59
What GLUT protein function is dependent on insulin?
GLUT4
60
What do muscle cells do with the large amount of glucose they uptake?
quickly phosphorylate it to glucose-6-phosphate by hexokinase (enzyme)
61
What muscle has very limited capacity to synthesize glycogen and how does it correct this issue?
cardiac and uses glucose-6-phosphate for immediate energy needs
62
how does the liver release glucose into the circulation?
through dephospho rylation by the glucose-6-phosphatase (enzyme)
63
what enzyme do muscle cells lack and how does this affect it?
glucose-6-phosphatase (meaning cannot export glucose) therefore glucose stored in the muscle as glycogen is used for glycolysis
64
what can cardiac and skeletal muscle express?
lipoprotein lipase on the cell surface that will bind to circulating chylomicrons (derived from the intestine) and VLDL (from the liver)
65
What hydrolyzes triacylglycerols transported by chylomicrons and VLDL?
lipoprotein lipase and the fatty acids are transferred into the cell
66
how are free fatty acids transported to muscle cells?
serum albumin
67
Where do triacylglycerols secreted in the liver come from?
catabolism of chylomicron remnants as well as hepatic synthesis of fatty acids from non lipid precursors (excess dietary glucose/fructose)
68
Why can't the brain use free fatty acids?
because these large molecules do not transport across the blood-brain barrier
69
what is the fed state?
lasting about 3 hours after a meal is ingested and characterized by insulin secretion
70
what is the postabsorptive state?
occurring from about 3 to 18 hours following the meal and accompanied by a rise in a glucagon secretion
71
what is fasting state?
lasting from 18 hours to about 2 days without additional intake of food and accompanied by further increases in glucagon
72
what is the starvation state or long-term fast?
a fully adapted state of food deprivation lasting longer than about 2 days
73
What is a primary indicator of the fed state?
the release of insulin by the beta-cells of the pancreas in response to increased BGL
74
what process continues to occur in the fed state when ample dietary glucose is present?
gluconeogenesis continues to function because of lactate returning to the liver from glycolysis constantly occurring in red blood cells and, under certain conditions, skeletal muscle
75
Why can't red blood cells oxidize fatty acids or glucose aerobically?
do not have mitochondria
76
What can red blood cells oxidize anaerobically?
glucose and produce lactate
77
What tissues cannot make glycogen or store triacylglycerols only relying on glucose for energy?
red blood cells and brain
78
when does the conversion of glucose to fatty acids occur?
only in the fed state when energy intake exceeds energy expenditure
79
with the onset of the postabsorptive state tissue can no longer?
derive energy directly from ingested macronutrients, but instead must begin to depend on fuel sources already in the body
80
what is the major provider during the postabsorptive state?
hepatic glycogenolysis is the major provider of glucose to the blood which transports it to other tissues for use as fuel
81
when glycogenolysis is occurring what diminishes?
the synthesis of glycogen and triacylglycerols in the liver is diminished and the de novo synthesis of glucose (gluconeogenesis) becomes a more important contributor in maintaining blood glucose levels
82
what is the glucose-alanine cycle?
alanine returns to the liver from muscle cells
83
what is alanine converted too?
pyruvate by the transfer of the amino group to a-ketoglutarate as the first step in the gluconeogenic conversion of alanine in the liver
84
where can alanine not be converted to glucose?
in the skeletal muscle
85
In the postabsorptive state, glucose provided to the muscle by liver comes from?
recycling of lactate and alanine and, to a lesser extent, from hepatic glycogenolysis
86
muscle glycogenolysis provides glucose as fuel only for?
muscle cells in which the glycogen is stored because muscle lacks the enzyme G6P to free glucose
87
once phosphorylated in the muscle, glucose is?
trapped there and cannot leave except as lactate or alanine
88
what can the liver do?
oxidize fatty acids for energy in the absence of insulin which promotes fatty acid synthesis rather than oxidation
89
During the fasting state amino acids from muscle protein breakdown provide?
the chief substrates for gluconeogenesis
90
of all the amino acids, only leucine and lysine cannot directly contribute to?
gluconeogenesis because they are ketogenic
91
what is one of the functions of the alanine-glucose cycle?
it removes the nitrogen from muscle during a period of high proteolysis and transports it to the liver in the form of alanine
92
what is another function of the alanine-glucose cycle?
transfers the carbon structure of pyruvate to the liver, where it can be made into glucose through gluconeogenesis - the synthesized glucose can be transported back to the muscle and used for energy by that tissue
93
What role does glutamine play and is increased during the fasting state?
a central role in transporting and excreting amino acid nitrogen
94
What are the important changes in metabolism during the starvation state that occur in order to spare protein?
accelerated lipolysis, increased use of fatty acids as fuel in certain tissues, increased use of glycerol for gluconeogenesis, and increased ketone body synthesis and utilization
95
Free fatty acids are released by adipose tissue and become the primary fuel for what organs?
kidneys, liver, heart and skeletal muscle
96
What is the primary source of carbon atoms for gluconeogenesis in the liver?
hydrolysis of triacylglycerols, providing glycerol
97
during starvation what organ becomes a major supplier of glucose through gluconeogenesis?
the kidneys
98
what do kidneys produce that help neutralize the acidity associated with ketone bodies?
ammonia
99
what helps spare valuable protein?
ketone bodies that are maintained at a high concentration by increased lipolysis and hepatic fatty acid oxidation, the need for glucose and gluconeogenesis is reduced
100
continued declines in glucose during fasting and starvation states cause?
greater secretion of glucagon
101
increased lipolysis in adipose tissue and subsequent rise in free fatty acids cause?
the liver to produce a significant amount of ketone bodies
102
what is the major anabolic hormone that impacts glucose, fatty acids and protein synthesis and storage?
insulin
103
What is the function of insulin?
increases glycogen synthesis in the liver and skeletal muscle and inhibits gluconeogenesis in the liver
104
As an anabolic hormone what does insulin do?
inhibits lipolysis in adipose tissue and proteolysis in muscle while promoting protein synthesis in muscle, liver and many other tissues, expressing insulin receptors.
105
If type 1 diabetes is left untreated the primary metabolic response include?
Increased lipolysis; increased use of fatty acids as fuel in most tissues; increased use of glycerol for gluconeogenesis; and increased ketone body production for energy in tissues that cannot use fatty acids
106
What do all metabolic effect of glucagon reflect?
the need to liberate stored energy for ATP production while maintaining blood glucose levels in the absence of dietary carbohydrate
107
what are the main tissues expressing glucagon?
liver and adipose tissue
108
What does glucagon do in the liver?
increases gluconeogenesis and glycogenolysis while inhibiting glycogen synthesis
109
what is the result of glucagon increasing?
more glucose can be released into the circulation and reverse effects of insulin and increases lipolysis in adipose tissue for release of free fatty acids into the circulation increases FAO and ketone body production in the liver as starvation progresses
110
What is Epinephrine produced by?
in the adrenal medulla from the amino acids phenylalanine and tyrosine
111
What is the function of epinephrine?
neurotransmitter in the nervous system and a stress hormone in the circulation
112
what can epinephrine do as a stress hormone?
can increase cardiac muscle contractions and increase vasodilation and blood flow to skeletal muscle and liver
113
what does the binding of epinephrine to alpha-receptor do to the organs?
pancreas: inhibits insulin secretion
liver/skeletal muscle: stimulates glycogen breakdown and inhibits glycogen synthesis
skeletal muscle: stimulates glycolysis
114
what does the binding of epinephrine to beta-receptors do to the organs?
pancreas: stimulates glucagon secretion
adipose tissue/skeletal muscle: stimulates lipolysis and inhibits FAS
115
what do the responses of epinephrine cause?
increased blood glucose and free fatty acids, allowing stored fuels to be used when dietary sources are insufficient
116
what is cortisol?
a corticosteroid hormone in the adrenal cortex from cholesterol
117
where is cortisol released?
from the adrenal cortex in response to low blood glucose levels
118
how does cortisol travel in the circulation?
bound to albumin and corticosteroid-binding globulin (transcortin)
119
what does cortisol do after being delivered to the target cells?
cortisol passes freely through plasma membranes, then binds to intracellular cortisol receptors residing in the cytosol
120
what does cortisol do in the liver?
stimulates gluconeogenesis and glycogenolysis
121
what does cortisol increase the activity of?
glucose-6-phosphatase, thus promoting the release of free glucose into the circulation
122
what does cortisol do in the skeletal muscle?
stimulates glycogenolysis and inhibits the translocation of GLUT4 to the cell membrane
123
what does cortisol stimulate in adipose tissue?
lipolysis, thus providing free fatty acids for energy use in the liver, kidneys, and cardiac and skeletal muscle
124
what does persistent high levels of cortisol stimulate?
protein breakdown in skeletal muscle, so amino acids may be used for gluconeogenesis
125
what is GH known and produced by?
somatotropin and by the anterior pituitary gland
126
what is GH secreted in response to?
variety of stimuli, including fasting and strenuous exercise
127
where are GH receptors present?
in the liver, adipose tissue, heart, skeletal muscle, kidney, brain and pancreas
128
what does GH stimulate in adipose tissue?
lipolysis and the release of fatty acids into circulation
129
What does GH increase in the liver?
triacylglycerol uptake from VLDL by inducing the expression of lipoprotein lipase and hepatic lipase
130
what is a function of GH?
to conserve protein by inhibiting protein breakdown while stimulating protein synthesis
131
what is adiponectin?
a protein hormone produced primarily by adipose cells
132
where does adiponectin exists?
in the plasma as a trimer, hexamer, or higher-order multimer
133
what does adiponectin do in skeletal muscle?
activates AMP-activated protein kinase (AMPK) thus increasing beta-oxidation of fatty acids for energy utilization
134
what does adiponectin increase?
the expression and activity of lipoprotein lipase on the cell surface, which promotes the hydrolysis of VLDL triacylglycerols and uptake of the resulting fatty acids for energy utilization
135
how does adiponectin promote blood glucose uptake?
by increasing GLUT4 translocation to the cell surface
136
what does adiponectin do in the liver?
suppresses glycogenolysis and gluconeogenesis, thus helping to maintain blood glucose concentration within the normal range
137
What are the main proteins in the muscle and what occurs when they're stimulated?
actin and myosin; myosin ATPase hydrolyzes ATP that provides the energy for muscle contraction
138
what are type 1 muscle fibers and what are they capable of?
oxidative and slow-twitch (slow but resistant to fatigue) fibers that are capable of oxidizing fatty acids and glucose to CO2 and H2O via the TCA cycle and oxidative phosphorylation
139
type 2 fibers
glycolytic (fast-twitch fibers) have significantly few mitochondria and less myoglobin
140
what muscle fiber has increase myosin ATPase and an active glycolytic pathway for rapid ATP replenishment in the absence of oxygen?
type 2
141
what roles does muscle 2 fibers play in glycogen?
increases ability to store glycogen and higher phosphofructokinase activity to support glycolysis
142
what are the metabolic characteristics of type 11a fibers?
lie between those of type 1 and 11x fibers (both glycolytic (fast) and oxidative (slow) ) - contain intermediate levels of mitochondria and myoglobin
143
what are 11a muscle fibers resistant too?
fatigue but have relatively high myosin ATPase activity and can contract rapidly when necessary
144
What does fast-twitch fibers allow?
rapid and intense muscle contraction
145
what does slow-twitch fibers allow?
fatigue-resistant fibers allow for muscular endurance
146
what does exercise of higher intensity activate?
AMPK resulting in increased lipolysis and fatty acid oxidation as well increased GLUT4 translocation to the muscle cell surface for glucose uptake independent of insulin
147
what will occur to the skeletal muscle during post absorptive and fasting state?
resting skeletal muscle will shift to using fatty acids, as glucose become more precious to other tissues
148
what are the 3 energy systems that supply ATP to the skeletal muscle?
- the ATP- phosphocreatine system
-the lactic acid system (anaerobic glycolysis)
-the oxidative system (aerobic metabolism)
149
what is the ATP- phosphocreatine system?
a cooperative system in muscle cells using the high-energy phosphate bond of phosphocreatine to quickly regenerate ATP
150
what is the lactic acid system?
involves the glycolytic pathway which anaerobically produces ATP through substrate phosphorylation by the incomplete breakdown of one molecule of glucose into two molecules of lactate in skeletal muscle
151
What is one cause of fatigue?
the quantity of lactate accumulates it lowers the pH of the blood and is one cause of fatigue
152
When can lactic acid system become the primary supplier of energy?
only after phosphocreatine stores in the muscle are depleted
153
What is the oxidative system?
involves the TCA cycle and oxidative phosphorylation to completely catabolize glucose, fatty acids and some amino acids to CO2 and H2O
154
what does resting muscle use as a preferred fuel source in the fed state?
blood glucose but can shift to using circulating fatty acids released from adipose tissue postabsorptive and fasting states.
155
what becomes the main energy source for high-intensity exercise lasting more than 1 hours?
plasma fatty acids released from adipose tissue
156
what is limited in it's ability to directly use amino acids for energy?
skeletal muscle
157
what type of exercise increases muscle protein breakdown and decreases protein synthesis?
endurance exercise
