Metabolism Part 3 Flashcards
1
Q
What cleaves sucrose in the intestine?
A
Sucrase-isomaltase
2
Q
What does loss of Sucrase-isomaltase cause?
A
Osmotic-fermentative diarrhea
3
Q
What gets Fructose into the enterocyte?
A
GLUT5
4
Q
Does GLUT5 saturate?
A
Yes, quickly
but fructose is inducible
5
Q
What transporter does Fructose use to enter the blood from the enterocyte?
A
Mostly GLUT2 (some GLUT5)
6
Q
What does Fructose get converted into in muscle?
A
Fructose-6-Phosphate
same as glucose
7
Q
What enzyme phosphorylates fructose in the liver?
A
Fructokinase
8
Q
What enzyme is skipped in the fructose pathway in the liver?
What enzyme is used instead?
A
PFK-1
Fructose-1-phosphate aldolase
aka ALDOLASE B
9
Q
Does fructose need insulin to enter the cell?
A
no
10
Q
What does the lack of PFK-1 cause in fructose metabolism?
A
Uncontrolled manufacture of Acetyl CoA and Citrate
11
Q
T/F
Excessive dietary intake of fructose may lead to decrease in available Pi
A
True
12
Q
The decrease of ATP in the cell due to fructose consumption caused by lack of available phosphate causes what?
A
Breakdown of residual ADP and AMP
results in hyperuricemia and gout
13
Q
What is the slow step in fructose metabolism?
A
Fructose-1-phosphate aldolase
aka Aldolase B
14
Q
Fructokinase pathologies tend to be ______, while Alsolase B (Fructose-1-phosphate aldolase) pathologies tend to be ________.
A
Benign
Severe
15
Q
What is the first step metabolite of Fructose in the muscle?
The liver?
A
Frc-6-P
Frc-1-P
16
Q
What does Mannose (after 2 steps) metabolize into?
A
Fructose-6-P
17
Q
What rxn traps glucose in a cell without committing an ATP?
A
Glc - Sorbitol
18
Q
What cells build up sorbitol during hyperglycemia?
A
Cells that store sorbitol (after conversion from glc) and can’t convert that into Fructose
19
Q
What are the effects of too much sorbitol?
A
Osmotic effects and swelling
20
Q
What happens to galactose when it enters the cell?
What is the main substrate here?
A
Galactose is broken down (first by Galactokinase) in 4 steps to G-6-P.
UDP-galactose-4-epimerase
21
Q
Once galactose has a UDP power pack on, what are its options?
A
Can enter glycolytic pathway or GNG
22
Q
What 3 (main) parts of the body are affected by fluctuations in Calcium concentration?
A
neurological
gastrointestinal
renal
23
Q
What is necessary for the absorption of dietary Calcium in the intestine?
A
Vitamin D
24
Q
What is the main source of stored Calcium in the body?
A
Hydroxyapatite
Ca10(PO4)5OH2
25
What does lack of Calcium (hypocalcenemia) cause?
Tetany (contractions)
26
What is the most concentrated protein in the blood?
| Name two things it carries.
Serum Albumin
```
Fatty Acids (SCFA, MCFA)
Calcium
```
27
T/F
| If Serum Albumin levels are abnormal, calcium can't be calculated
False
28
What corrects the measurement of Calcium if Serum Albumin are off?
Corrected Calcium (equation)
29
What are the 3 main areas that maintain calcium homeostasis?
Gastrointestinal tract
Kidney
Bone
30
How much calcium goes into bone every day?
| How much comes out?
500 mg
| 500 mg
31
What are the 2 types of ways calcium moves out of the lumen?
Transcellular transport (duodenum)
Paracellular (jejunum and ilium)
32
What type of transport out of the lumen is increased if calcium intake is low?
Transcellular (this can be controlled)
33
Why does Vitamin D deficiency often lead to Calcium deficiency?
poor absorption without Vita D
34
What are 3 foods that absorb calcium in the gut and prevent Vitamin D from doing its job?
rhubarb, spinach, and chard.
35
What are the main hormones that reciprocally regulate calcium?
PTH, Calcitonin, and Vitamin D
| Vitamin D is a hormone
36
UV light hits cholesterol to make?
| How is this activated?
Cholecalciferol
2 Hydroxylations to form Calcitriol
(aka 1,25 dihydroxycholecalciferol)
37
The key enzyme in Vitamin D activation controlled by PTH levels is?
1-Alpha-Hydroxylase
38
Where do the 2 hydroxylations that create activated Vitamin D occur?
Liver (1st hydroxylation)
| Kidney (2nd hydroxylation forming Calcitriol)
39
What molecule, under the direct control of Vitamin D, mediates the transport of Calcium across the enterocyte (apical to basolateral)?
Calbindin-D9k
40
What is the rate limiting step of calcium transport?
Calbindin-D9k moving Calcium across the enterocyte
41
What 2 ways does Calcium enter the blood from the enterocyte?
via an ATP pump
(1 Ca++ out / 2 H+ in)
Na+/Ca++ exchanger
(3:1)
42
What often mediates intracellular calcium?
Are these under the control of Vitamin D?
```
Troponin C (muscle)
Calmodulin (other cells)
```
*theses are calcium binding proteins
43
What has greater effects, PTH or Calcitonin?
PTH
44
Where is Calcitonin produced?
| How long is the polypeptide?
Parafollicular (C) cells of Thyroid
32 AA and linear
45
T/F
| Transcellular transport of Calcium is regulatable, while Paracellular is not.
True
46
Where does Paracellular transport take place?
Across tight junctions
| and down the concentration gradient
47
What 3 things does Calcitriol (Vita D) control in the enterocyte?
Transporters on luminal (apical) side
Transporters on basolateral side
Calbindin (which takes it across the cell)
48
What are the epithelial Calcium channels called that go from lumen to enterocyte?
TRPV5 and TRPV6
49
What is the main cause of Hypocalcemia?
Vitamin D deficiency
rickets!
50
What are the 2 main counter regulatory hormones to insulin?
Glucagon
| Epinepherine
51
Name 5 catabolic compounds that counter the action of insulin:
```
Glucagon
Epinepherine
Norepinepherine
Cortisol
Growth Hormone
```
52
What is the rate limiting step of Epinepherine synthesis and release?
What is the rxn?
Tyrosine Hydroxylase
Tyrosine > Dopa
53
Where does the rate limiting step of epinepherine synthesis occur?
Adrenal Medulla
| chromaffin cells
54
What type of membrane transduction does epinepherine work through?
GPCR
| G-Protein compound receptor
55
What are epinepherine's effects in the:
pancreas?
adipose?
Pancreas - inhibits insulin release and stimulates glucagon release
Stimulates lipolysis
56
What are epinepherine's metabolic effects in the liver and muscle?
Liver: increase GNG
Muscle: increase glycolysis
57
What is produced at the islets of Langerhans?
Glucagon - by the Alpha cells
Insulin - by the Beta cells
also, Somatostatin by the Delta cells
58
T/F
| The pancreatic hormones have only endocrine effects.
False
also have local autocrine and paracrine effects
59
What is given to diabetics to counteract hypoglycemia?
Glucagon
60
What is Proglucagon broken down into in the pancreas and in the intestine?
pancreas: Glucagon
intestine: GLP-1 (and also GLP-2 and Oxyntomodulin)
61
What is the major target of Glucagon?
| What is the mechanism to enter the cell?
Liver
| G-protein second messengers
62
What are glucagon's effects on:
glycogen phosphorylase
glycogen synthase
PFK-1?
increase
decrease
decrease
63
What are glucagon's effects on:
Frc-1-6-BP
Pyruvate kinase
Triacylglycerol lipase
increase
decrease
increase
64
Insulin has 1/2 life of 5 minutes. How can we more easily measure insulin release clinically?
C-peptide from the "Prepro" hormone
65
Describe insulin's effects on target cells.
Insulin binds outside
| Tyrosine Phosphorylated
66
After phosphorylation, what is the most important downstream effect of Insulin binding?
Translocation of GLUT4 to the membrane
| this allows Glc to enter cell
67
What is one of the effectors of GLUT4 inside the cell after Insulin binding?
P13-kinase
68
T/F
| Insulin features prominently in the uptake of ions such as K+ and PO4-3.
True
69
What senses glucose in the pancreas?
GLUT2 (ferrari)
| Glucokinase
70
What is the pathway leading to insulin release at a Beta cell?
```
Glc enters through GLUT2
Glycolysis creates ATP
ATP shuts down K+ channel
depolarization opens Ca++ channel
Calcium stimulates insulin release
```
71
What is the insulin and glucagon response following a high carbohydrate meal?
a high protein meal?
carb: Insulin up, glucagon down
protein: Insulin AND glucagon up
72
What 3 Amino Acids stimulate the release of Insulin?
AGR
alanine
glycine
arginine
73
How do A, G, and R AA's depolarize Beta cells?
Alanine & Glycine - Na+ symport depolarizes
R (arginine) - dedicated transport protein. Arg is a cation and depolarizes cell directly
74
What class of substances is responsible for the greater insulin response when taken orally?
Incretins
| remember: GLP-1 and the Gila monster
75
What is the coenzyme in catecholimine rate limiting step?
| epinepherine
Tetrahydrobiopterin > Dihydrobiopterin
76
What is the function of GLP-1 in the liver?
remember: this comes from Proglucagon
Enhances Insulin effects
also Gila monster drug - (Incretins)
77
What are the body's priorities after a meal?
1. Replenish glycogen stores
2. store fat
3. increase protein reserves
78
What are the body's 2 biggest goals when hungry?
1. Brain and CNS (GNG, etc)
| 2. Conserve protein
79
What are the 2 main sources of fuel during fasting (1 hr after meal)?
Liver glycogenolysis - glc
| Adipose Lypolysis - fat
80
In a progression of fasting (beyond a few hours), what does the liver also make (besides breaking down glycogen)?
GNG pathways are activated
81
If a fast continues for 2 or more days, what occurs in the muscle and brain?
Muscle switches off ketone bodies (oxidizes fatty acids) so they can go to the brain.
82
When is glc not the sole fuel for the brain?
prolonged starvation
83
Why does skeletal muscle produce lactate when actively contracting?
Glycolysis much faster than CAC so buildup of product.
84
What does resting muscle preferentially metabolize?
Fatty acids
85
T/F
| Heart has glycogen reserves
false
86
What is the main source of fuel for the heart?
fatty acids
| ketone bodies/lactate CAN fuel the heart
87
What is the glycolytic intermediate in adipose tissue necessary for synthesis of TAG's?
(somehow leads to CoA derivative transfer to glycerol-3-P)
dihydroxyacetone phosphate
88
Why are Fatty Acids released into the blood if glucose levels are low?
No glycerol-3-Phosphate for TAG synth
89
What organ provides half GNG during starvation?
Kidney
90
What are the main precursors to GNG in liver?
Lactate and Alanine from muscle
glycerol from adipose
glucogenic AA's from diet
91
What does the liver make ketone bodies out of in the fasting state?
Fatty Acids
92
What prevents Fatty acids from entering the mitochondrial matrix?
Malonyl CoA
| this is fed state and FA's exported to adipose
93
What allows the passage of Fatty Acids into the mitochondrial matrix to make ketone bodies under low energy conditions?
Low levels of Malonyl CoA
94
The liver absorbs most of the AA's from the blood. What is the priority for use?
Protein synthesis
| rather than catabolism
95
What three AA's are processed in muscle rather than liver?
Leucine, Isoleucine, and Valine
| LIV
96
What does the liver use as its main energy source?
Alpha-Ketoacids
| glycolysis are building blocks and ketogenics are exported
97
Does Adipose tissue undergo Beta-oxidation?
Negative
exports FA's for breakdown in other tissues
98
T/F
| Glucagon inhibits Insulin (but not vise versa)
FALSE
Insulin inhibits glucagon
Glucagon does not inhibit insulin
(if glucagon levels are high reasonable to assume meal is just around the corner)
99
How long do glycogen stores last?
12-18 (maybe 24) hours
100
What does muscle preferentially use for energy if Glucagon is high?
FAT
101
What does skeletal muscle use for energy in the first few days of not eating?
Fat, Ketone bodies (reach highest level at Day 3), Fat
| this allows ketone bodies to go to the brain
(GNG decreases and spares muscle)
102
What 2 energy sources remain constant in fasting Day 3 to 40?
Adipose lypolysis
| Ketone body formation
103
Why does urea excretion go down with prolonged fasting?
Preserve water and muscle (as much as possible)
104
Why does the liver lag in the uptake of Glc after a meal?
leaves it for peripheral tissues
| stays in GNG mode for glycogen synth
105
What is the Master Switch (energy sensor enzyme)?
What activates?
What does it do?
AMPK
high levels AMP
```
produces ATP
(and shuts down processes using ATP)
```
106
What, specifically, does AMPK do?
phosphorylates rate-limiting enzymes in energy using/producing pathways
(senses cellular energy levels)
107
Define:
polyuria
polydipsia
polyphagia
Lots of urine
thirsty
hungry
108
What part of insulin can be detected longer?
C-peptide
109
What lipid enzyme does insulin stimulate?
Acetyl CoA Carboxylase
110
Why are you sleepy after a meal?
Insulin actually makes blood slightly hypoglycemic
111
Frequency of Ketosis in Type 1 vs Type 2 diabetes?
Type 1 - common
| Type 2 - rare
112
Why is Type 1 diabetes unresponsive to oral drugs treating hypoglycemia?
No insulin whatsoever
113
What cells are totally eliminated (eventually) in Type 1 diabetes?
Beta cells
114
What cell receptor needs insulin for fat uptake?
Lipoprotein Lipase
115
What two states characterize type 2 diabetes?
insulin secretion deficit
| insulin resistance
116
The curve of insulin output in Type 2 diabetes is due to:
Burnout of Beta cells
117
Why is ketoacidosis less of an issue with Type 2 diabetes?
There's still a little insulin
118
How is hyperglycemia measured?
Hemoglobin A1c
119
What 3 conditions must be met for sorbitol to do real damage?
1. Diabetic
2. tissue must be able to take up glc without insulin
3. tissue lacks ability to take sorbitol to fructose
120
What enzyme makes sorbitol from glucose?
Aldose reductase
121
What comprises metabolic syndrome?
Hyperglycemia
low HDL
Apple fat
high TAG's
122
Preproinsulin is synthesized in the:
| Proinsulin breaks down to Insulin and C-peptide in the:
ER
| Golgi
123
What makes up insulin structurally?
Alpha and Beta chains attached by two disulfide bonds
124
What type of adipocytes are more hormonally responsive and have a greater impact on the liver?
Abdominal
125
What receptor increases with the amount of fat you store?
Lipoprotein Lipase
note: this sticks around after losing weight so more efficient at storing fat
126
Obesity is a disease of chronic...
Inflammation
127
Name 3 Adipokines that increase with obesity and one that does not.
Leptin, TNf-alpha, IL-6
Adiponectin
128
What two Adipokines induce insulin resistance?
TNF-alpha
| IL-6
129
Does leptin increase with weight?
It should be proportional to adipose tissue.
130
What does a lot of leptin signal?
| What does low levels of leptin signal?
Leptin signals the brain and tells you you're full, so low amounts signals to slow down, don't eat, stay on the couch.
131
What suggests human obesity isn't related to the amount of Leptin?
Trials negative (positive with mice and that kid in Turkey)
This suggests the brain's resistance to Leptin
132
What adipokine decreases inflammation?
Adiponectin
133
What structure in the brain is responsible for integrating hunger/satiety signals?
Hypothalamus
134
What structure in the brain is associated with overeating and obesity?
Damage to
Ventromedial or
Paraventricular nuclei
(VM and P of the hypothalamus)
135
What part of the hypothalamus is often damaged in weight loss and anorexia?
Lateral Hypothalamic
136
What two types of neurons in the hypothalamus regulate appetite?
Orexigenic (go eat)
| Anorexigenic
137
Name 2 Orexigenic neurons:
```
Neuropeptide Y (NPY)
Agouti related protein (AgRP)
```
(these nerves signal the proteins they're named for)
138
What are the two Anorexigenic neurons in the hypothalamus?
One has an important derivative:
POMC (pro-opiomelanocortin)
CART (cocaine/amphetiamine regulated transcript)
note: POMC processed to alpha-MSH (melanocyte stimulating hormone)
139
What does Leptin stimulate and inhibit in the hypothalamus?
stimulates anorexigenics:
POMC/MSH
inhibits orexigenics:
NPY/AgPR
140
What acts in a similarly to Leptin in the hypothalamus?
Insulin
| can't go far wrong thinking Insulin and Leptin do the same thing
141
Name 2 molecules in the intestine that act as satiety signals to the brain?
CCK
GLP-1
(note: GLP-1 signals brain and pancreas)
142
What are the functions of GLP-1?
acts as satiety signal to the brain
incretin for insulin and pancreas
(increases insulin secretion, biosynth, B-cell proliferation, B-cell survival)
143
What is the peptide hormone that acts as an appetite stimulant originating in the stomach?
What are its actions on the brain?
Ghrelin
binds/stimulates NPY/AgPR/GABA neurons
(orexigenic = glucagon-like)
144
Under normal circumstances what occurs in cells in response to weight gain?
Cells grow larger (hypertrophy)
145
Under what circumstances do we see new adipocytes forming instead of just increasing in size?
Severe obesity
146
Where is alcohol generally oxidized?
80-90% in the liver
147
What part of the GI tract absorbs alcohol?
| What part is most effective?
```
All parts
small intestine (because of large surface area)
```
148
Does alcohol require a transporter to enter cells?
NO
149
T/F
| 15% alcohol eliminated in sweat, urine, feces, breath, saliva, and lactation.
False
| 10%
150
What is the main enzyme used by "naive" alcohol consumption?
Where does this occur?
Alcohol dehydrogenase
Cytosol
151
What system is used in habitual drinkers to metabolize alcohol?
Where does this take place?
Cytochrome P450
(MEOS)
Smooth ER
152
What are the major and minor routes of ethanol oxidation?
Major:
Alcohol dehydrogenase in cytosol
Cytochrome P450 (MEOS) in Smooth ER
Minor:
Catalase dependent oxidation in Peroxisome
Gastric Oxidation (first pass) in stomach
153
What do the metabolic routes of ethanol processing have in common for both habitual and "naive" drinkers?
Both seriously deplete NAD+
154
dehydrogenase =
redox
155
What are the two main steps of ethanol metabolism?
Where do they occur?
cytosol:
Ethanol > Acetaldehyde
(Alcohol dehydrogenase)
mitochondria:
Acetaldehyde > Acetate
(Aldehyde dehydrogenase - ALDH2)
156
Why is acetaldehyde damaging to the cell?
creates many adducts
| increases ROS
157
What does ethanol consumption do to the following rxn:
pyruvate + NADH > lactate + NAD+
Le Chat pushes toward lactate due to 10 fold increase in NADH
158
What is the product Acetate (from ethanol met.) converted into?
Acetyl CoA
*requires GTP
159
Cytochrome P450 aka:
CYP2E1
160
What can ROS/Acetaldehyde from ethanol metabolism damage?
proteins
causes lipid peroxidation
Mutagenic/Carcinogenic
DNA repair
161
What cofactor does Alcohol Dehydrogenase carry?
Zinc metalloprotein
162
How many genes code for how many classes of Alcohol Dehydrogenase and which one has the lowest Km?
7 genes
5 classes
```
lowest Km (highest affinity) is Class I in the liver
*this is the major one
```
163
What is a major contributor to the variation we see in ability to metabolize alcohol?
ALDH2 variants
164
Pretty much all the biochemical downstream side effects of ethanol ingestion is due to:
Decreased NAD+/NADH ratio
165
Why does alcohol cause hypoglucemia?
excess NADH prevents GNG in liver
166
What are 4 major consequences of decreased NAD+/NADH ratio?
Hypoglicemia (GNG suppressed)
Lactic Acidemia
Ketonemia (lots Acetyl CoA, no glycogen, no GNG)
Hyperuricemia (ketones/lactate compete with uric acid for renal pump)
167
Why does alcohol cause dehydration?
inhibits ADH
168
How does alcohol affect protein trafficking?
| 4 ways
Fatty liver (acetaldehyde adducts tubulin)
Protein secretory/plasma mem. assembly impaired
VLDL export decreased
*receptor mediated endocytosis affected
169
What does alcohol consumption do to the major excitatory and inhibitory neurotransmitters?
```
Inhibits Glutamate (excitatory)
- uncoordination, speech, memory
```
```
Enhances GABA (inhibitory)
- anxiety reduction and sleep
```
170
Are most alcoholics malnourished?
no
171
What 3 vitamin deficiencies do alcoholics often have?
Thiamin (B1)
Folic Acid
Vitamin A
172
What syndrome is associated with decreased thiamin levels due to alcohol consumption?
Wernicke-Korsakoff syndrome
173
Folic acid depletion leads to...
anemia
174
Why is Vitamin A deficiency seen upon alcohol consumption?
Retinol (Vitamin A) degraded by MEOS
resembles alcohol just enough
175
T/F
| Alcohol has a greater overall effect on women
True
176
Which vitamins are water soluble?
B and C
total of 9
177
What are the fat soluble vitamins?
ADEK
178
What is the most important Vitamin?
D
*calcium and bloot clotting
179
What is Vitamin A important for?
growth, immune system, vision
180
What is Vitamin C important for?
Collagen/scurvy
*hydroxylation step in collagen synth
181
Vitamin B1:
name
pathology
Thiamine
Beriberi, Wernicke Korsikoff
182
Vitamin B2
name
pathology
Riboflavin
mouth lesions and dermatitis
183
B5
name
pathology
Pantothenate
Hypertension
184
B6
name
pathology
```
Pyridoxal phosphate
(*aminotransferases)
```
Depression, confusion, convulsions
185
B7
name
pathology
Biotin
rare rash/fatigue
186
B9
name
pathology
Folate
anemias
187
B12
name
pathology
Cobalmin
anemias
(*Odd Homo Meth)
188
B3
name
pathology
NAD - Niacin
Pellagra (dermatitis, depression, diarrhea)
189
Vitamin A
name
pathology
Retinol
Night blindness
190
Vitamin D
name
pathology
Calcitriol
Rickets, osteomalacia
191
Vitamin E
name
pathology
tocopherol
Erythrocyte hemolysis (newborns)
192
Vitamin K
function
pathology
synth prothrombin and clotting factors
difficulty in blood coagulation (takes a long time)
