Metabolism Flashcards
(150 cards)
1
Q
*** Where does the conversion of pyruvate to acetyl CoA take place?
A
matrix of the mitochondria
2
Q
What are the 4 fates of acetyl CoA?
A
1) oxidize acetyl groups in the CAC
2) lipgenesis
3) ketogenesis
4) cholesterologenesis - and then cholesterol can be turned into steroids
3
Q
** preferred fuel of liver?
A
fa, glucose, aa
4
Q
** preferred fuel of skeletal muscle?
A
resting- fa
exertion- glucose
5
Q
** preferred fuel of brain?
A
fed- glucose
starvation- ketone bodies + glucose
6
Q
** preferred fuel of adipose tissue
A
fa
7
Q
** preferred fuel of heart muscle
A
fa
8
Q
5 major dietary carbohydrates, where they come from, what breaks them down
A
amylose- potatoes, rice, corn, bread- maltase sucrose- sugar, desserts- sucrase lactose- milk, milk products- lactase fructose- fruit, honey glucose- fruit, honey
9
Q
carb metabolism in RBCs
A
- lack mitochondria so its only glycoslysis
* glucose - g6p- lactate OR pentose phosphate*
10
Q
carb metabolism in brain
A
- absolute requirement for glucose
* glucose - g6p (can do PP pathway)- pyruvate- acetyl CoA- CAC- Co2 ***
11
Q
carb metabolism in muscle and heart cells
A
- major store of glycogen (which they can’t mobilize into tissue)
- glucose- g6p (PP pathway, storage as glycogen)- pyruvate (enter lactic acid cycle)- acetyl CoA- CAC **
12
Q
carb metabolism in adipose tissue
A
- main purpose is turn glucose into fat
* glucose- g6p (PP pathway, storage as glycogen)- pyruvate- acetyl CoA- fat *
13
Q
carb metabolism in hepatocytes
A
- liver regulates glucose production
- glucose- g6p (PP pathway, glycurides, storage as glycogen)- pyruvate (enter lactic acid cycle)- acetyl CoA- Fat OR CAC **
14
Q
what is the main difference between GLUTs and SGLTs?
A
GLUT- down a concentration gradient
SGLT- against a concentration gradient, using co-transport with sodium
15
Q
difference between SGLT1 & 2
A
1- transports glucose & galactose, found in intestinal mucosa & kidney tubules
2- only glucose, only kidney
16
Q
what is the main insulin dependent glucose transporter? is it high or low affinity? what tissues is it found in?
A
GLUT4
heart, muscle, adipocytes
high affinity
17
Q
what is the insulin independent low affinity transporter in liver?
A
GLUT2
low affinity, high capacity - works in both directions
glucose sensor for pancreatic beta cells
18
Q
what does GLUT5 transport?
A
fructose in skeletal muscle, adipose tissue, brain, sperm, RBCs
19
Q
definition of glycolysis
A
metabolic pathway where a single glucose molecule converts into 2 pyruvates, 2 ATP, 2 NADH, 2 H20 (happens during hyperglycemia with high insulin)
20
Q
definition of glycogenolysis
A
breakdown of glycogen to glucose-1-p and glucose in the liver and muscles by glycogen phosphorylase
21
Q
definition of gluconeogenesis
A
results in the generation of glucose from a non-carbohydrate carbon substance such as pyruvate, lactate, glycerol and glucogenic amio acids (happens during hypoglycemia when there is increase glucagon)
22
Q
definition of glycogenesis
A
formation of glycogen from glucose (happens during hyperglycemia when insulin is high)
23
Q
***** what are the 2 main processes that happen during the fasting state? 2 processes during the fed state?
A
fasting: glycogenolysis, gluconeogenesis
fed: glycolysis, glycogenesis
24
Q
*** where in the cell does glycolysis occur?
A
only in cytoplasm of ALL cell types (NOT mitochondria)
25
*** what are the 3 key enzymes which have one way reactions?
1. hexokinase/glucokinase (glucose-g6p) (uses ATP)
2. PFK1- (f6p-f1,6bp) (uses ATP)
3. pyruvate kinase- phosphoenolpyruvate to pyruvate (makes an ATP!)
26
what does glycolysis produce energy in the form of?
ATP, NADH
27
**** characteristics of hexokinase
- found in all cell types
- allosterically inhibited by own product
- non-inducible (found in constant amounts)
- has low Km
- saturated easily
28
*** characteristics of glucokinase
- found in liver & pancreas
- inhibited by downstream product (f6p) which translocates gk to nucleus
- synthesis is induced by insulin
- high km (low affinity- able to handle large amounts of glucose in liver)
29
what are the allosteric regulators of hexokinase?
g6p inhibits
30
what are the allosteric regulators of PFK1?
- f-2,6-bp major activator (made using PFK2)
- citrate- major inhibitor (CAC intermediate)
- ATP- major inhibitor
- indirectly, glucagon & epinephrine inhibit in liver (phosphorylates kinase domain of PFK2)
- indirectly, epinephrine actives in heart and skeletal muscle (phosphorylates phosphatase domain of PFK2)
31
what are the allosteric regulators of pyruvate kinase?
- f-1,6-bp activates
- ATP inhibits
- alanine inhibits
* glucagon & epinephrine inactivate via induced phosphorylation
32
what is the pancreatic hormone that leads to the inhibition of hepatic glycolysis?
glucagon
33
how does glucagon inhibit hepatic glycolysis?
indirectly inhibiting PFK1 (phosphorylates PFK2) and directly inhibiting pyruvate kinase and decreasing synthesis of the 3 irreversible enzymes
34
relationship between insulin, glucagon, epinephrine; do they increase or decrease synthesis of the 3 irreversible enzymes?
increased insulin=
increased cAMP=
decreased glucagon & epinephrine
= increased synthesis of 3 irreversible enzymes!!
35
what are the differential effects of epinephrine?
- inhibits hepatic glycolysis- phosphorylates kinase domain of PFK2
- stimulates cardiac/muscle glycolysis- phosphorlates phosphatase domain
36
when would you expect to see high LDH levels?
lactose dehydrogenase is high well cells are damaged- e.g. during myocardial infarction, ishcemic stroke
37
normal serum ratio of lactate to pyruvate
10:1
38
what are the allosteric inhibitors of PDH (pyruvate dehydrogenase)?
it's reaction products- acetyl CoA and NADH
39
T/F phosphorylating PDH renders it inactive
True
40
what are some factors that cause PDH phosphorylation? dephosphorylation?
phosphorylation- NADH, acetyl CoA
| dephosphorylation- coASH, NAD+, ADP, pyruvate
41
*** vitamin cofactors that participate in the PDH reaction?
B1- thiamine
B5- pantothenate
B2- riboflavin
B3- niacin
42
*** list 3 things that would cause high lactate and high pyruvate in the blood
1. arsenic poisoning (inhibits lipoic acid shuttle)
2. thiamine deficiency
3. genetic deficiency in PDH
43
*** what would a deficiency in fructose aldose cause? what foods should the person avoid?
- get build up in f-6-p, phosphates tied up, can't generate ATP, can't power ATP pumps, cells die
- avoid fruit & honey
44
*** what would a deficiency of galactokinase or other galactose enzymes cause? what foods should be avoided?
- formation of galactitol- cataracts
- high blood & urinary galactose
- high g-1-p levels- hepatic & brain dysfunction
- avoid lactose
45
*** what is the range in which fasting glucose levels are maintained?
above 60 mg/100mL
| below 110 mg/100 mL
46
** 3 names of important stages for glycolysis
priming- ATP investment
splitting- 2 G3ps
oxidoreduction-phosphorylation- ATP earnings
47
** which reaction requires a steady supply of NAD+? where does it come from in anaerobic respiration? aerobic respiration?
glyceraldehyde 3 p dehydrogenase
- anerobic- lactate/ethanol production (cytosol)
- aerobic- metabolite shuttle system
48
** low levels of NADH increase/decrease lactate formation
decrease
49
what are the steps of the citric acid cycle?
* between oxidation steps that produce NADH
# between oxidation steps that produce FADH2
$ by the one that produces GTP
& where C's are lost via CO2
```
ACoA
citrate
isocitrate
*&
alphakg
*&
succinyl Coa
$
succinate
#
fumerate
malate
*
oxaloacetate
```
50
which CAC enzyme is in the inner mitochondrial membrane?
succinate dehydrogenase
51
** how many high energy phosphates generated per turn of the CAC? (ATP+GTP)
10 (3 NADH, 1 FADH2, 1 ATP)
52
** types of coarse control for the CAC?
- ATP (needed to make NAD+)
- acetyl CoA supply
- oxaloacetate
53
** fine control- isocitrate dehydrogenase
inhibited by NADH and ATP
| stimulated by ADP
54
** fine control- alphaketogluterate dehydrogenase
inhibited by ATP, GTP, NADH, succinyl CoA
| stimulated by calcium
55
where does TCA provide precursors?
```
citrate- FAs & sterols
alphaKg- AAs/NTs
succinyl coa- heme
malate- gluconeogenesis
oxaloacetate- AAs
```
56
*** where can the TCA be replenished?
- alphakg- glutamate from AAs
- succinyl coa from propionyl coa (val/ile)
- fumerate- AAs
- oxaloacetate- aspartate & pyruvate
57
how does rat poison work?
fluroacetate converted to flurocitrate, which inhibits aconitase (transformation of citrate-isocitrate)
58
2 pathways that form free glucose?
1st- glycogen degradation
| 2nd- gluconeogenesis (NON CARB)
59
** where in the body does glucogneogenesis primarily occur?
liver & kidney- localize it so it doesn't compete with glycolysis
60
** what is the major source of ATP for gluconeogenesis? AKA gluconeogenesis REQUIRES ATP
oxidation of fatty acids
61
When you use glucogeneic AA's as opposed to lactate you need more/less ATPs?
need MORE (10 vs 6) b/c energy is needed to dispel amino groups given off via urea cycle
62
*** what are the 4 enzymes that catalyze the 3 irreversible steps of glycolysis? (aka how you do reverse glycolysis to do gluconeogenesis?)
1- pyruvate caboxylase
2- PEP carboxykinase
3- Fructose 1,6 bisphosphate
4- glucose 6 phosphatase
63
what factors stimulate glucogenesis as opposed to glycolysis?
increase in cAMP caused by high glucagon/epi and increased synthesis of key 4 enzymes
64
what factors stimulate glycolysis as opposed to gluconeogenesis?
increased insulin or decreased cAMP, as well as increased synthesis of key 3
65
** how does ethanol ingestion make you hungry?
it inhibits gluconeogenesis, causing hypoglycemia via over-production of NADH, converting pyruvate/oxaloacetate to malate/lactate
66
*** which 3 main sources does acetyl CoA come from?
- glycogen/glucose/pyruvate
- triglycerides/fatty acids
- protein/amino acids
67
** where are the 3 places acetyla CoA goes?
CAC
ketone bodies
fatty acids; sterols
68
** what are some symptoms of children with pyruvate dehydrogenase deficiencies?
elevated serum levels of lactate, pyruvate and alanine, which produce a chronic lactic acidosis
69
** what are some examples of substrates that are used in gluconeogenesis to make glucose?
NON-CARB: pyruvate, lactate, glycerol, glucogenic amino acids
70
** what is considered the activated form of pyruvate?
oxaloacetate- intermediate on the way back to PEP
71
** glucogenic precursors- pyruvate
2 lactate, alanine
72
** glucogenic precursors- oxaloacetate
aspartate
73
** glucogenic precursors- triose phosphates (ga3p)
glycerol
74
** what are some differences between the cori cycle and the glucose-alanine cycle?
cori- muscle/RBCs- lactate goes to liver, makes glucose, costs 6 ATPs
glucose-alanine- muscle- alanine goes to liver, makes glucose, costs 10 ATPs
75
** what does a genetic deficiency in pyruvate carboxylase cause?
failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis; elevated serum levels of lactate, pyruvate and alanine, which produce a chronic lactic acidosis
76
** what are the different uses for muscle & liver glycogen? what are the different effects you would see if their activities were impaired?
muscle- production of ATP via g6p in cell- decreased ability to exercise
liver- maintenance of blood glucose- decreased blood glucose levels
77
** what is the key enzyme lacking in muscles with regard to glycogen storage?
glucose 6 phosphatase- glycogen can't be converted all the way back to glucose
78
**what is the rate limiting enzyme for glycogen degredation? what enzyme regulates it?
- glycogen phosphorylase a (-PO4)
| - regulated by phosphorlyase kinase a
79
** what is the rate limiting enzyme for glycogen synthesis? what enzyme regulates it?
- glycogen synthase a
| - phosphoprotein phosphatase (activates) and calmodulin dependent protein kinase (inhibits)
80
** in both cases, phosphorylation of both glycogen phosphatase and glycogen synthase promote the storage or breakdown of glycogen?
breakdown
81
** what are the actions of insulin on the glycogen cycle?
- synthase: stimulates phosphoprotein phosphatase, removes the phosphate from synthanse converting it from B to A, makes glycogen
- phosphorylase: stimulates the removal of a phosphate from a, get inactive b form, no storage
82
** what are some allosteric regulators of the phosphorylase/synthase pathways?
phosphorylase:
- b: activated by AMP
- a: inhibited by ATP, activated by glucose
synthase:
- b: activated by G6P
83
** what are the actions of cAMP on the glycogen cycle?
- cAMP produced by glycogen/epi stimulation
- increases the activity of phosphorylase kinase, activates glycogen phosphorylase, degrade glycogen
- inhibits the activity of phosphoprotein phosphatase, don't activate glycogen synthase
84
** what are the actions of Ca2+ on the glycogen cycle?
- Ca2+ released with sustained muscle contraction
- activates phosphorylase kinase, which activates glycogen phosphorylase (glycogen degradation)
- activates calmodulin dependent protein kinase which inactivates glycogen synthase (no storage)
85
what two hormones increase the concentration of blood glucose?
glucagon & epinephrine
86
what are the specific functions glucagon & epinephrine inhibit and activate?
- inhibit glycolysis (inhibits PFK2, reducing PFK1 function, inhibits pyruvate kinase)
- activates hepatic glucogenogenesis (increases fructose 1,6,bp, inhibits pyruvate kinase)
- inhibits glycogen synthesis
- activates hepatic glycogenolysis (breakdown of glycogen by activating glycogen phosphorylase and phosphorylase kinase)
87
** what is the main system that uses the pentose phosphate pathway?
RBCs
88
** what does the metabolism of glucose in the pentose phosphate pathway produce?
- NADPH- lipid biosynthesis; maintains glutathione in a reduced state that helps protect the RBCs against oxidative damage
- ribose 5 phosphate- DNA/RNA synthesis
- glycolysis intermediates
89
** what is the rate limiting enzyme in the pentose phosphate pathway? what does a deficiency in this enzyme cause?
glucose 6 phosphate dehydrogenase (g6dp)
| - causes hemolytic anemia b/c RBCs can't reduce NADPH (which maintains glutathione in a reduced state)
90
what is the physiological condition that favors fatty acid biosynthesis?
fed state, high insulin
91
** what is the rate limiting enzyme in fatty acid biosynthesis?
acetyl-CoA carboxylase
92
** what are the hormones that activate/inhibit aCoA carboxylase?
activate- insulin
| inhibit- *epinephrine & glucagon
93
** what are the allosteric activators and inhibitors of aCoA carboxylase?
activate- citrate & biotin
| inhibit- palmitoyl-CoA, AMP
94
what are some factors that increase/decrease the synthesis of aCoA carboxylase?
- increased: carbs, insulin, thyroid hormone
| - decreased: high fat, fasting, glucagon
95
** what is the product of the acetyl CoA caboxylase reaction? what does it inhibit? what cofactor serves as a carrier of activated CO2?
malonyl CoA
inhibits beta oxidation
biotin
96
what is the name of the 7 enzyme complex that catalyzes the formation of fatty acids? what is it's allosteric activator?
fatty acid synthase
| activated by fructose 1,6, bisphosphate
97
what are some things that increase/decrease the synthesis of fatty acid synthase?
- increased by high carbs/free fat
| - decreased by high glucagon, hight fat diet
98
what are the two essential fatty acids?
alpha linolenic acid & linoleic acid
99
how are fatty acids stored?
as triacylglycerols (TAGs)
100
what are the 5 things fatty acid biosynthesis required?
```
1- acetyl coa groups transported as citrate
2- acetyl coa caboxylase
3- biotin
4- FA synthase complex
5- NADPH
```
101
**which glucose transporter do you see on hepatic cells for glycogen production? on muscle cells?
- hepatic: glut 2, works both ways, insulin independent
| - muscle- glut 4, only takes glucose in after a meal (insulin dependent)
102
** pathway for glycogen synthesis
glucose __> g6p __> glucose1-p __> UDP-glucose __> glycogen
103
** what factors cause reactive oxidative species to rise?
oxidative drugs, infections, favism (lots of fava beans)
104
which hormone mobilizes FA from adipose TAGS?
HSTL- hormone sensitive triacylglycerol lipase
105
what is a major activator of the hormone that mobilizes FAs and via which pathway? lesser activator?
- epinephrine via PKA, cAMP pathway
| ACTH
106
which are some inhibitors of the hormone that mobilizes FAs?
```
insulin via dephosphorylation
and PGEs (prostaglandins)
```
107
what three factors are required for normal HSTL activity?
thyroid hormones & adrenal cortical hormones & perilipin to coat surface of fat droplets
108
what are the two products of TAG breakdown?
fatty acids and glycerol
109
what does the released glycerol stimulate?
gluconeogenesis in liver
110
what do the released fatty acids stimulate/inhibit?
- inhibit fatty acid synthesis
- stimulate beta oxidation (no malonyl coa)
- stimulate the production of ketone bodies and ATP
- ATP inhibits glycolysis, stimulates gluconeogenesis
111
what are some good users of fatty acids?
liver, kidney cortex, heart, skeletal muscle
112
tissues that cannot use fatty acids directly
brain, RBCs, nervous system, adrenal medulla, lens
113
what does each cycle of mitochondrial b-oxidation generate?
1 acetyl-COA
1 NADH
1FADH2
114
what is the comparison of phosphates produced from beta oxidation of palmitate and metabolism of glucose?
106 ATP vs 36-38 ATP
115
what is the name of the protein that transports long chain fatty acids into mitochondrial matrix for beta oxidation?
caratine
116
what is the rate limiting enzyme for beta oxidation? what is it inhibited by?
CPT1; malonyl CoA
117
when are ketone bodies formed?
when beta oxidation production of acetyl CoA > utilization (high beta oxidation, high activity of HSTL, high levels of fatty acids)
118
why is liver the only tissue in which ketone bodies can be synthesized?
b/c rate limiting enzyme is only in liver- HMG-COA synthase
119
can livers use ketone bodies as fuel?
NO- don't have acetoacetate:succinylCoA CoA transferase
120
what is the end product of ketone body utilization?
2 acetyl CoA
121
3 key regulatory steps for the break down of fatty acids
1- HSTL- inhibited by epi, stimulated by insulin
2- acetyl CoA carboxylase- stimulated by citrate/insulin, inhibited by glucago/epi
3- CPT1- inhibited by malonyl CoA
122
in which way is dietary cholesterol packaged and where?
with TAG, in chylomicrons (least dense transport molecule) in intestinal cells
123
in which way is synthesized cholesterol packaged and where?
with TAG, in VLDL molecules in liver cells
124
how is cholesterol used?
- cell membranes
- bile acids
- steroid hormones
125
what vitamin is made from cholesterol?
vitamin D
126
what are some steroid hormones that come from cholesterol?
progesterone, 17 beta estadiol, testosterone, cortisol, aldosterone, dehydroepiandrosterone
127
what is the cholesterol biosynthesis pathway?
acetyl CoA --> mevalonate --> C15 --> squalene --> lanosterol --> cholesterol
128
what is the rate limiting enzyme in cholesterol biosynthesis?
HmG-CoA reductase
129
what factors regulate HmG-CoA reductase?
statins (lipitor)
cholesterol (transcription/enzyme stability)
AMP, glucagon (phosphorylation)
mevalonate (translation/enzyme stability)
- insulin activates
130
what is the rate limiting enzyme in bile acid synthesis?
7 alpha hydroxylase
131
what does an excess of cholesterol lead to
inhibits HMG CoA (bio-synthesis of cholesterol)
Activates ACAT (storage)
activates 7 alpha hydroxylase (bile)
132
ratio of esterified to free cholesterol
70 esterified :30 free
133
T/F esterifying cholesterol makes it more soluble for storage
F- cholesterol already is hydrophobic, adding the ester group makes it MORE hydrophobic
134
which enzyme catalyzes the esterification of cholesterol for storage?
ACAT
| acyl-CoA cholesterol acyl transferase
135
What are lipoproteins made of?
apolipoproteins + TAGs, cholesterol, cholesterol esters
136
what are the 5 major class of lipoproteins?
chylomicron, VLDL, IDL, LDL, HDL
137
Chylomicrons are a good indicator of ____ because they are formed in the ______
dietary fat, intestines
138
VLDLs are a good indicator of ____ because they are made in the ______
dietary carbohydrates; liver (endogenous TAG)
139
which apolipoprotein activates LPL?
Apo-C II
140
which apolipoprotein clears remnants of VLDL/chylomicrons after TAGs have been hydrolyzed
Apo-E
141
which apolipoprotein activates LCAT and turns cholesterols into cholesterol esters?
A1
142
T/F Apoproteins are made in the adipose tissue
False
143
What does b-48 do? b-100?
b48- chylomicron secretion
| b100- LDL receptor binding
144
what does LDL do?
delivers fat/ cholesterol to liver & other cells (steroid-making)
145
what does HDL do?
accepts cholesterol, esterifies it & transports to liver for excretion; carries apolipoproteins
146
how is cholesterol taken up into cells?
B100s bind to LDL receptors in clathrin-coated pits, are endocytosed
147
how does a defect in LDL receptors affect serum cholesterol, intracellular cholesterol, cholesterol biosynthesis
increases serum cholesterol
decreases cholesterol biosyntheses
decreases intracellular cholesterol esters
148
two mechanisms of reverse cholesterol transport (mature HDLs)
a) CETP (transfer protein) mediates transfer from HDL - VLDL/IDL/chylomicron
b) HDLs taken up by liver by receptor mediated endocytosis
149
LDL or HDL is highly sensitive to oxidation?
LDL
150
major apoproteins for each of the 5 classes
1. chylomicron- B48, ACE
2. VLDL- B100, ACE
3. IDL- B100, CE
4. LDL- B100
5. HDL- A's (CE)
