Integration of Metabolism Flashcards
(171 cards)
1
Q
What are the functions of the liver?
A
processes fats, carbs & proteins from the diet
synthesizes & distributes lipids, ketones bodies, & glucose
converts excess nitrogen to urea
2
Q
How is the metabolism of the body integrated?
A
nervous & hormonal signals
3
Q
Which part of the body is considered the savings account? Explain this.
A
Adipose Tissue
stores 100X more energy than glycogen
Note: when you are fasting–>you see more free fatty acids in your plasma.
4
Q
Which part of the body is considered the checking account?
A
the liver
5
Q
How much energy does the brain normally consume per day? How much energy does it consume when you are fasting?
A
Normally: 90g/day (20% of the resting energy)
Fasting: 30g/day
6
Q
When are insulin levels the highest?
A
after a high carb meal
7
Q
What stimulates the synthesis of insulin?
A
glucose & amino acids potentiate it.
8
Q
What are the 3 main targets of insulin?
A
muscle, adipose, liver
9
Q
Insulin is the hormone of the well-fed state. What does this mean?
A
It stimulates the storage of excess nutrients as glycogen or fat. Note: we don’t store protein.
10
Q
What types of enzymes are stimulated by insulin?
A
glucose metabolizing enzymes
via phosphorylation or synthesis of these enzymes
11
Q
What types of glucose transporters does the liver use?
A
GLUT 2
12
Q
What is the main important enzyme of the glucose phosphorylation pathway?
A
Glucokinase
13
Q
What process does PFK1 & pyruvate kinase promote?
A
glycolysis
14
Q
What are 3 important enzymes that promote gluconeogenesis?
A
PEPCK
F16BPase
G6Pase
15
Q
What process does glycogen synthase regulate?
A
glycogen synthesis
16
Q
What is the main enzyme involved in glycogenolysis?
A
glycogen phosphorylase
17
Q
What pathway are the following enzymes involved in: Acetyl CoA Carboxylase, ATP-Citrate Lyase, Malic Enzyme?
A
Fatty Acid synthesis
18
Q
What is the main important enzyme in the pentose phosphate pathway?
A
G6P dehydrogenase
19
Q
Insulin in the liver causes an increase/decrease in the following pathways: Glucose Phosphorylation Glycolysis Gluconeogenesis Glycogen Synthesis Glycogenolysis Fatty Acid Synthesis Pentose Phosphate Pathway
A
Glucose Phosphorylation: increases Glycolysis: increases Gluconeogenesis: decreases Glycogen Synthesis: increases Glycogenolysis: decreases Fatty Acid Synthesis: increases Pentose Phosphate Pathway: increases
20
Q
What are the general effects of insulin on adipose tissue?
A
stimulates glycolysis
stimulates FA synthesis & storage
prevents fat breakdown
21
Q
What is the rate limiting step in adipose tissue & skeletal muscle of glucose metabolism?
A
Glut 4 receptors. Km =1 mM
most important enzyme for glucose uptake
22
Q
What is the most important enzyme for glycolysis?
A
PFK1
23
Q
G6P dehydrogenase is super important in which pathway?
A
pentose phosphate pathway
24
Q
What is the most important enzyme in pyruvate oxidation?
A
pyruvate dehydrogenase
25
What is LPL really important for?
triglyceride (FFA) uptake
26
What is the most important enzyme in lipolysis?
HSL
27
```
Insulin in adipose tissue increases/decreases the following pathways:
glucose uptake
glycolysis
pentose phosphate pathway
pyruvate oxidation
triglyceride uptake
TAG synthesis
lipolysis
```
```
glucose uptake: increases
glycolysis: increases
pentose phosphate pathway: increases
pyruvate oxidation: increases
triglyceride uptake: increases
TAG synthesis: increases
lipolysis: decreases
```
28
What is the most important enzyme in glucose uptake in skeletal muscle?
GLUT 4 receptors
29
What is PFK1 super important in?
glycolysis
30
What is the most important enzyme in glycogen synthesis?
glycogen synthase
31
What is glycogen phosphorylase super important for?
glycogenolysis
32
```
Insulin in skeletal muscle increases/decreases the following processes:
glucose uptake
glycolysis
glycogen synthesis
glycogenolysis
protein synthesis
```
```
glucose uptake: increases
glycolysis: increases
glycogen synthesis: increases
glycogenolysis: decreases
protein synthesis: increases
```
33
What are 2 places in the body where glucose uptake is non-insulin dependent? Which glucose receptors do they use?
brain: Glut 3
RBCs: Glut 1
34
Pathways that remove excess fuels from the blood are active in the fed state. What are these pathways?
Glycogen Synthesis
Glycolysis
Fatty Acid Synthesis
Lipogenesis
35
We are talking about the effect of insulin on this process. Which parts of the body does this happen in? Which enzyme(s) are affected?
*Glucose Uptake
Increases
* *adipose tissue, skeletal muscle, liver
* *targets GLUT 4 transporters in adipose tissue & skeletal muscle
* *targets glucokinase in the liver
36
We are talking about the effect of insulin on this process. Which parts of the body does this happen in? Which enzyme(s) are affected?
*glycogen synthesis
Increases
* *liver, muscle
* *targets glycogen synthase
37
We are talking about the effect of insulin on this process. Which parts of the body does this happen in? Which enzyme(s) are affected?
*Glycogenolysis
Decreases
* *liver, muscle
* *targets glycogen phosphorylase
38
We are talking about the effect of insulin on this process. Which parts of the body does this happen in? Which enzyme(s) are affected?
*Glycolysis & Acetyl-CoA Production
Increases
* *liver, muscle
* *targets PFK1 (targets PFK2 to stimulate PFK1)
39
We are talking about the effect of insulin on this process. Which parts of the body does this happen in? Which enzyme(s) are affected?
*Fatty Acid Synthesis
Increases
* *liver
* *targets Acetyl CoA Carboxylase
40
We are talking about the effect of insulin on this process. Which parts of the body does this happen in? Which enzyme(s) are affected?
*TAG synthesis
Increases
* *adipose tissue
* *targets lipoprotein lipase
41
What is the function of glucagon? Where is it secreted from?
secreted from pancreatic alpha cells
| **function is to maintain blood glucose
42
What second messenger does glucagon use?
cAMP
43
What is the response of glucagon to hypoglycemia? What is the response of glucagon to hyperglycemia?
Hypoglycemia: glucagon increases 2-3 fold
Hyperglycemia: glucagon decreases to 1/2 of original
44
If you are trying to affect gluconeogenesis, which 3 enzymes do you target?
PEPCK
F16BPase
G6Pase
45
What is the main enzyme targeted when affecting glycogen synthesis? What is the main enzyme targeted when affect glycogenolysis?
Glycogen Synthesis: glycogen synthase
| Glycogenolysis: glycogen phosphorylase
46
If you are trying to change fatty acid oxidation-->which enzyme do you alter? If you are trying to change fatty acid synthesis-->which enzyme do you alter?
Fatty Acid Oxidation: CPT1
| Fatty Acid Synthesis: Acetyl CoA Carboxylase
47
Where is the main place that glucagon acts in the body?
the liver
48
```
What are the effects of glucagon in the liver on the following pathways:
glycolysis
gluconeogenesis
glycogen synthesis
glycogenolysis
FA synthesis
FA oxidation
```
glycolysis: decreases
gluconeogenesis: increases
glycogen synthesis: increases
glycogenolysis: decreases
FA synthesis: increases
FA oxidation: decreases?
49
What do catecholamines do?
involved in acute & chronic stress response
| **main effect: mobilization of glycogen & fat for muscle use
50
What are the main types of catecholamines? Where are they secreted from?
Norepi & Epi from the adrenal medulla
51
Starting from tyrosine...how do you get Epi?
Tyrosine-->L-DOPA-->Dopamine-->Norepi-->Epi
52
What are some things that prompt catecholamine release?
hypoglycemia
pain
hypoxia
hemorrhage
53
```
What does the presence of epinephrine in the liver do to the following processes?
Glycolysis
Gluconeogenesis
Glycogen Synthesis
Glycogenolysis
FA synthesis
```
```
Glycolysis: decreases
Gluconeogenesis: increases
Glycogen Synthesis: decreases
Glycogenolysis: increases
FA synthesis: decreases
```
54
How does the presence of Epi in the liver act to decreases glycolysis?
By turning the PFK2 into PFK1.
55
How does the presence of Epi in the liver act to increases gluconeogenesis?
```
inhibiting pyruvate kinase (don't continue glycolysis)
increasing F26BPase (decreases activity of PFK1)
```
56
Why would you want to increase the activity of F26BPase if you are trying to increase gluconeogenesis?
if you increase F26BPase activity, you get less F26BP. With less F26BP you get less stimulation of PFK1. This tells the glycolysis to chill out & the gluconeogenesis to step up.
57
How does the presence of Epi in the liver act to decrease glycogen synthesis?
glycogen synthase is phosphorylated. This reduces its activity
58
How does the presence of Epi in the liver act to increase glycogenolysis?
glycogen phosphorylase is phosphorylated. This increases its activity.
59
How does the presence of Epi in the liver act to decrease fatty acid synthesis?
acetyl CoA carboxylase is phosphorylated. this reduces its activity
60
Aside from glycogen phosphorylase...what are other ways that glycogenolysis is stimulated?
Glycogenolysis can also be stimulated via vasopressin, oxytocin, Ang II thru Ca++ or phosphatidylinositol bisphosphatase.
61
What do alpha adrenergic receptors have to do with epi in the liver?
The epi acts on these alpha adrenergic receptors and prompts them to raise the Ca++ levels. This activates a phosphorylase kinase that is sensitive to Ca++ & Calmodulin.
Note: a lot of the effects of epi in the liver involved phosphorylation-->good to have a kinase on the team!
62
Which receptors are activated when epi comes in contact with adipose tissue?
beta adrenergic receptors-->increases cAMP
63
What is the effect of epinephrine on adipose tissue?
```
increases lipolysis (via HSL)
decreases TAG uptake from lipoproteins (via LPL)
```
64
What is the effect of epinephrine on the pancreas?
it increases glucagon secretion
| decreases insulin secretion
65
Which receptors are activated by epinephrine acting on the skeletal muscle?
beta adrenergic receptors
| this raises cAMP levels
66
```
What does epinephrine do in the skeletal muscle to the following processes:
glycolysis
glycogen synthesis
glycogenolysis
TAG uptake from lipoproteins
```
glycolysis: increases!!!!
glycogen synthesis: decreases
glycogenolysis: increases
TAG uptake from lipoproteins: increases
67
Whoa! Crazy...epinephrine stimulates glycolysis in skeletal muscle. How?
the kinase activity that is kicked off by cAMP does something weird in skeletal muscle. Phosphorylation of PFK2-F26BPase here stimulates the kinase activity. therefore, you end up with more F26BP. This stimulates PFK1 & glycolysis
68
What are the highlights of the overall effect of epinephrine on metabolism? which substances does epinephrine act a lot like?
Acts a lot like glucagon.
Stimulates glycogen breakdown in muscle & liver
stimulates gluconeogenesis in the liver
Stimulates lipolysis in adipose tissue.
increases secretion of glucagon & decreases secretion of insulin from the pancreas.
69
How does the presence of Epi in the liver act to decrease glycogen synthesis?
glycogen synthase is phosphorylated. This reduces its activity
70
How does the presence of Epi in the liver act to increase glycogenolysis?
glycogen phosphorylase is phosphorylated. This increases its activity.
71
How does the presence of Epi in the liver act to decrease fatty acid synthesis?
acetyl CoA carboxylase is phosphorylated. this reduces its activity
72
Aside from glycogen phosphorylase...what are other ways that glycogenolysis is stimulated?
Glycogenolysis can also be stimulated via vasopressin, oxytocin, Ang II thru Ca++ or phosphatidylinositol bisphosphatase.
73
What do alpha adrenergic receptors have to do with epi in the liver?
The epi acts on these alpha adrenergic receptors and prompts them to raise the Ca++ levels. This activates a phosphorylase kinase that is sensitive to Ca++ & Calmodulin.
Note: a lot of the effects of epi in the liver involved phosphorylation-->good to have a kinase on the team!
74
Which receptors are activated when epi comes in contact with adipose tissue?
beta adrenergic receptors-->increases cAMP
75
What is the effect of epinephrine on adipose tissue?
```
increases lipolysis (via HSL)
decreases TAG uptake from lipoproteins (via LPL)
```
76
What is the effect of epinephrine on the pancreas?
it increases glucagon secretion
| decreases insulin secretion
77
Which receptors are activated by epinephrine acting on the skeletal muscle?
beta adrenergic receptors
| this raises cAMP levels
78
```
What does epinephrine do in the skeletal muscle to the following processes:
glycolysis
glycogen synthesis
glycogenolysis
TAG uptake from lipoproteins
```
glycolysis: increases!!!!
glycogen synthesis: decreases
glycogenolysis: increases
TAG uptake from lipoproteins: increases
79
Whoa! Crazy...epinephrine stimulates glycolysis in skeletal muscle. How?
the kinase activity that is kicked off by cAMP does something weird in skeletal muscle. Phosphorylation of PFK2-F26BPase here stimulates the kinase activity. therefore, you end up with more F26BP. This stimulates PFK1 & glycolysis
80
What are the highlights of the overall effect of epinephrine on metabolism? which substances does epinephrine act a lot like?
Acts a lot like glucagon.
Stimulates glycogen breakdown in muscle & liver
stimulates gluconeogenesis in the liver
Stimulates lipolysis in adipose tissue.
increases secretion of glucagon & decreases secretion of insulin from the pancreas.
81
Why do people today have a lot of cortisol in their system?
b/c they have a lot of stress in their lives & it is a dangerous world. It is a chronic stress response.
82
What is the main mechanism of action of cortisol? Which substance does it work synergistically with? What class of substances does it belong to?
Cortisol-->Glucocorticoids
works thru gene regulation (more of an effect on the hours-days scale)
works w/ epinephrine
83
What are the main effects of cortisol in the body?
Increased TAG degradation in adipose tissue
Breakdown of muscle protein
Gluconeogenesis increase in the liver
Glycogen synthesis increase
84
How does cortisol increase gluconeogenesis in the liver?
thru increasing the synthesis of PEPCK
85
What building block does cortisol use to stimulate an increase in glycogen synthesis?
uses all the extra G6P from gluconeogenesis
86
What is the net effect of cortisol in the body?
restores blood glucose
| glycogen stores increase
87
What are the negative side effects of cortisol in the body?
overtime it destroys muscle & bone
| it also impairs the endocrine & immune system
88
What type of hormone is growth hormone?
it is a peptide hormone, not a glucocorticoid.
89
What is the basic effect of growth hormone on the body?
increases free fatty acid availability for energy generation
| spares the oxidation of glucose & amino acids
90
What is the half life of GH?
20-50 minutes
91
What are the direct effects of growth hormone on adipose tissue?
increased epinephrine sensitivity
decreased insulin sensitivity
decreased fatty acid esterification
92
What are the indirect effect of growth hormone on adipose tissue?
increased lipogenesis
increased plasma free fatty acids & glycerol
decreased TAG synthesis
decreased glucose uptake
93
What are the direct effects of growth hormone in the liver?
increased protein synthesis
increased free fatty acid oxidation
increased gluconeogenesis
decreased glycolysis
94
What are the indirect effects of growth hormone in the liver?
Increase in IGF-1
Increased ketogenesis
increased glycogen synthesis
95
What are the direct effects of growth hormone in skeletal muscle?
increased free fatty acid oxidation
| increased amino acid transport (pos nitrogen balance)
96
What are the indirect effects of growth hormone in skeletal muscle?
decreased glucose use (glucose sparing)
decreased glucose uptake
decreased glycolysis
increased protein synthesis (protein sparing)
97
What are the half lives of T3 & T4?
T3: 1-1.5 days
T4: 7 days
98
What are the main effects of thyroid hormone on the body?
an increase in fuel consumption
| an increase in sensitivity of receptors that have insulin counter-regulatory effects
99
Growth hormone on which 2 tissues causes an impaired insulin post receptor signaling?
skeletal muscle
| adipose tissue
100
What is the effect of thyroid hormone on the pancreas?
it increases the sensitivity of beta cells & prompts insulin release
101
What is the direct effect of thyroid hormone on adipose tissue?
an increase in epinephrine sensitivity
102
What are the indirect effects of thyroid hormone on adipose tissue?
So...this one is a little more complicated.
Usu: an increase in lipolysis
Sometimes: if there is enough insulin & glucose available-->an increase in TAG synthesis
103
What are the direct effects of thyroid hormone on muscle?
an increase in gene expression
| an increase in epinephrine sensitivity
104
What are the indirect effects of thyroid hormone on muscle?
an increase in glucose uptake (prompted by insulin)
increased protein synthesis
increased glycogenolysis
increased glycolysis
105
What are the direct effects of thyroid hormone on the liver?
increased glycolysis
increased cholesterol synthesis
with more cholesterol available-->increased bile salts
an increased sensitivity to epinephrine
106
What are the indirect effects of thyroid hormone on the liver?
increased free fatty acids-->formation of more TAGs
107
What percentage of glucose is metabolized by the liver?
20-30% of dietary glucose
108
What happens to most of the glucose that is processed by the liver?
most of it is processed into glycogen
109
Can the liver get TAGs from chylomicrons?
No, b/c they don't have lipoprotein lipase. Therefore, they can only take in TAGs from remnant particles.
110
Describe the basics of the conversion of carbs to fats in the liver.
Glucose-->Acetyl CoA-->Fatty Acids
111
When does the liver make VLDL?
At all times.
112
What happens to fatty acids when they are in liver mitochondria?
they undergo beta oxidation & form acetyl CoA
113
What are the 2 possible fates of Acetyl CoA?
can either go into TCA or ketogenesis
114
Malonyl CoA inhibits which enzyme?
Carnitine Palmitoyl Transferase 1
115
What are 2 things that stimulate Acetyl CoA carboxylase?
insulin
| citrate
116
When does the liver start becoming a net producer of glucose?
3-4 hours after a meal...
117
After a 12 hour fast, what happens to Carnitine palmitoyl transferase 1? how?
its activity increases
| it is simulated by glucagon, its activity is no longer inhibited by the presence of malonyl CoA
118
What happens to acetyl CoA carboxylase after a 12 hour fast?
its activity decreases b/c there is increased acyl CoA to inhibit it & there is less citrate around to activate it
it is also phosphorylated via glucagon/epi signaling.
119
After a meal...what are the activity levels of carnitine palmitoyl transferase 1 & acetyl CoA carboxylase?
CPT1 inhibited
| Acetyl CoA Carboxylase activity higher
120
After a 12 hours fast...what are the activity levels of CPT1 & Acetyl CoA carboxylase?
CPT1 stimulated
| Acetyl CoA carboxylase inhibited
121
After a 4 day fast, what are the main sources of blood glucose?
amino acids
| lactate
122
After a 4 day fast you get a higher rate of beta oxidation...what 2 things does this supply?
ATP
| NADH
123
What happens to TCA & ketone body formation after a 4 day fast?
TCA decreases
| ketogenesis increases
124
What converts HMG CoA to acetoacetate?
3-hydroxy-3-methyl-glutaryl-CoA lyase
| this enzyme increases after a 4 day fast
125
The liver converts carbs to what 2 things?
Carbs converted to glycogen & fat
126
During fasting, what are the 2 things that the liver supplies to the body?
glucose
| ketone bodies
127
What is the function of the enzyme HSL?
hormones sensitive lipase is found on adipose tissue. its function is to mobilize fats. Breaks TAGs into free fatty acids.
128
Which processes are especially active in the starved state?
```
glycogenolysis
gluconeogenesis
lipolysis
proteolysis
ketogenesis
```
129
What kind of an effect does insulin have on adipocytes after a mixed meal?
```
inhibits HSL: TAG breakdown
Glut4 glucose uptake stimulated
stimulates LPL: uptake of fatty acids
fatty acid synthesis increases
TAG synthesis increases
```
130
What are the ways by which fatty acids increase in adipocytes after a mixed meal?
LPL stimulation: just take up more FFA.
| More GLUT4 glucose uptake-->acetyl CoA-->fatty acids.
131
How is TAG synthesis increased in adipocytes after a mixed meal?
A bunch of glucose uptake & DHAP formed. This turns into glycerol phosphate.
FFA & glycerol phosphate form TAGs in adipocytes.
132
What happens to adipocytes during fasting?
during fasting you have more epinephrine-->stimulates HSL. More TAG breakdown to FFA, which are released. Glycerol is also released during the breakdown.
133
What happens to the glycerol that is released from adipocytes during fasting?
it goes to the liver for gluconeogenesis
134
What happens to free fatty acids that are released from adipocytes during fasting?
some go to muscles & other tissues for oxidation
| some go to the liver for ketogenesis
135
When a person is well fed, what is the state of their muscle?
strong
| well-supplied
136
When a person is fasting...what is the state of their muscle?
glucose sparing
| protein degradation
137
What is a tissue where insulin does not stimulate LPL?
muscle
138
What is the source of energy for the brain during starvation?
ketone bodies
139
After a meal...what substances go to the liver right away?
glucose
fatty acids
amino acids
140
What does the liver do with glucose in a well-fed state?
some stored as glycogen
others converted to acetyl CoA--fatty acid synthesis. This forms TAGs that take a ride in a VLDL to adipose & muscle tissue.
Requires NADPH
141
Where does the liver get the NADPH that is required to turn glucose into TAGs?
from glucose oxidation via the pentose phosphate pathway.
142
What does the liver do with extra AA lying around?
turns into pyruvate or acetyl CoA for fatty acid synthesis, lipid synthesis
143
How can lactate be transformed into usable energy? Where were the main sources of lactate?
by converting it into glucose in the liver
| **main sources: muscle, RBCs
144
So when someone is fasting...their muscles still need ATP energy. They get this in a way that is glucose sparing. How can that be done?
the muscle gets it ATP thru glycogenolysis instead of blood glucose
"glucose sparing"
145
Early on in fasting...the brain can still get glucose...but only from 1 source. What is that source?
breakdown of liver glycogen
146
Explain how liver glycogen is broken down for usable energy early on in fasting.
liver glycogen broken down
get a bunch of glucose-1-phosphate
G1P is converted into G6P
converted into free glucose-->released into the bloodstream.
147
What happens to the body during starvation?
proteins in the liver & muscle are broken down.
adipose tissue breaks down TAGs.
AA & glycerol liberated from this catabolism used for gluconeogenesis.
148
What do most tissues use for fuel during starvation?
ketone bodies
149
What does the liver use for fuel during starvation?
fatty acids
150
What is the main source of blood glucose during starvation?
liver (80%)
| kidneys (20%)
151
Where do the ketone bodies that most tissues use for their energy during starvation come from?
they come from the liver.
| liver uses FA as fuel. Takes excess acetyl CoA & turns it into ketone bodies. This is used by other tissues!
152
In the starved state, what percentage of gluconeogenesis has to do with AA? How much glucose does this process produce per day?
1/2 done w/ AA
| produces 80-160 grams glucose/day
153
Of the glucose that is produced by gluconeogenesis in the starved state: how much will be used by the brain?
Of the ketone bodies that are produced in the starved state: how much will be used by the brain?
1/2 the glucose will be used by the brain
| 70% of the ketones will be used by the brain
154
When a certain percentage of the body's nitrogen has been catabolized...it is too late to recover. What is the percentage?
when 1/3 of the body's nitrogen has been catabolized-->too late.
155
Why do patients with type I diabetes tend to be so thin?
b/c there isn't sufficient insulin to turn off lipolysis. keep eating away the fat.
156
```
In patients with Type I Diabetes...insulin is away, so glucagon will play. What does that mean for the following processes:
glycolysis
gluconeogenesis
glycogen synthesis
glycogenolysis
FA synthesis
FA oxidation
```
glycolysis: down
gluconeogenesis: up
glycogen synthesis: down
glycogenolysis: up
FA synthesis: down
FA oxidation: up
157
Describe the effects of glucagon on a patient with Type I Diabetes. Focus: liver
Liver--makes a bunch of glucose, but can't make glycogen
increased beta oxidation of free fatty acids
a bunch of extra acetyl CoA-->ketone bodies abound.
Possible ketoacidosis
158
Describe the effects of glucagon on a patient with Type I Diabetes. Focus: Adipose tissue
can't take up glucose b/c of the lack of GLUT 4 translocation
increased lipolysis-->increased plasma FFA
159
Describe the effects of glucagon on a patient with Type I Diabetes. Focus: muscle tissue.
can't take up glucose b/c of the lack of GLUT 4 translocation
160
What is the main danger of Type I Diabetes?
increase in ketone body formation-->possible ketoacidosis.
161
What is the main danger of Type II Diabetes?
not ketoacidosis
| hyper-osmolarity of the blood can dehydrate the brain & lead to a coma.
162
What are the main treatment options for Type II Diabetes?
diet & exercise
| oral hyperglycemics
163
In patients with Type II Diabetes, what's the deal with their metabolism?
adipose & muscle tissue don't take up glucose--no GLUT 4 receptors
Liver CAN make glycogen in this case.
Adipose tissue lipolysis does NOT increase substantially
LPL activity decreases
plasma lipoproteins increase
164
What are xenobiotics? What in the body usu metabolizes them?
foreign chemicals that must be removed from the body (could be foreign but from a plant, or could be drug)
Cytochrome P450
165
How are xenobiotics excreted from the body?
thru the urine or bile if they are hydrophilic
| if they are hydrophobic-->made to be hydrophilic & then excreted...
166
How are lipophilic xenobiotics made water soluble? Where does this happen?
liver, intestines, lungs
| happens in a 2 phase rxn
167
Describe Phase I of the reaction to turn a lipophilic xenobiotic water-soluble before excretion.
metabolite is oxidized
hydroxyl groups added
Cytochrome P450 involved
requires NADPH
168
What is the exact reaction of Phase I?
Substrate-H + O2 + NADPH + H+-->Substrate-OH + H2O + NADP+
169
Where is Cytochrome P450 usu found?
in the smooth ER of the liver & the lungs
170
What happens in Phase II of the lipophilic xenobiotic reaction?
metabolite is conjugated with a hydrophilic molecule to inactivate it & carry it out.
171
What are some of the hydrophilic molecules that lipophilic xenobiotics are often conjugated to?
```
glucuronic acid
sulfate
glycine
glutamine
glutathione
```
