Lectures 1-6 Flashcards
(197 cards)
1
Q
4 functions of carbohydrates
A
- Metabolic fuel
- Components of DNA/RNA
- Components of proteins
- Cell wall structure in bacteria/plants
2
Q
Carbohydrates are transported in blood in what form?
A
alpha-D-glucose (cyclic)
3
Q
What is the storage form of glucose called?
A
Glycogen
4
Q
2 ways glucose can be metabolized anaerobically
A
- glycolysis
2. pentose phosphate pathway
5
Q
2 ways in which RBCs can metabolize glucose
A
- glycolysis
- pentose phosphate pathway
(must be anaerobic)
6
Q
glucose can be stored as glycogen in what parts of the body?
A
- liver
2. muscle
7
Q
if glucose is metabolized aerobically, what is it metabolized to? what does this process require?
A
becomes CO2. requires that the cell use 02
8
Q
liver cells have the special function of synthesizing what? from what starting materials?
A
can synthesize glucose, from lactic acid and some amino acids.
9
Q
The 1-C of glucose is referred to what? why?
A
referred to as the reducing carbon, because it can be oxidized easily.
10
Q
What is Benedicts reagent? What was it used for?
A
Used in past to measure ‘reducing sugar’ in urine. Benedicts reagent contains a blue salt that turns red in the presence of 1-C of glucose. 1-C is oxidized, Benedicts is reduced.
11
Q
If glucose is oxidized at C-1, what will it become?
A
Gluconic acid
12
Q
If glucose is oxidized at C-6, what will it become?
A
Glucuronic acid
13
Q
What causes cataracts in diabetes?
A
Accumulation of sorbitol in the lens, since the lens lacks sorbitol dehydrogenase (glucose –> sorbitol –> fructose) and there is a lot of glucose around.
14
Q
How is a glycosidic bond formed?
A
elimination of water between 2 sugar molecules
15
Q
How is HbA1C formed?
A
Glucose in blood reacts with NH2 groups in hemoglobin.
16
Q
What is HbA1C a measure of?
A
long-term glucose levels in blood.
17
Q
Where is Sialic acid found?
A
Cell surface glycoproteins
18
Q
what are glycosaminoglycans?
A
polysaccharides with carboxyl, sulfate and amino groups
19
Q
What are proteoglycans?
A
proteins attached to glycosaminoglycans. Function as joint lubricants and structural components in connective tissue.
20
Q
What type of glycosidic bonds can humans metabolize?
A
Can metabolize alpha-1,4 glycosidic bonds but not beta-1,4 glycosidic bonds. hence cannot digest cellulose.
21
Q
Describe glycogen
A
storage form of glucose. Glucose molecules linked by alpha-1,4 and alpha-1,6 glycosidic bonds.
22
Q
glycolysis is used to achieve what?
A
ATP production, pyruvate/lactate production.
23
Q
the pentose phosphate pathway is used for what?
A
to create NADPH, ATP, and pentose
24
Q
Glycogen synthesis is used to accomplish what?
A
storage of glucose
25
glycolysis: aerobic or anaerobic?
can be either
26
pentose phosphate pathway: aerobic or anaerobic?
anaerobic
27
citric acid cycle accomplishes what? aerobic or anaerobic?
recovers maximum amount of energy from carbohydrate. can convert glucose or lactate to CO2. requires oxygen.
28
Gluconeogenesis accomplishes what?
synthesis of glucose. allows liver to maintain constant blood glucose levels.
29
How is glucose trapped inside cells?
by phosphorylation
30
what cells have hexokinase?
all cells
31
what cells have glucokinase in addition to hexokinase?
liver, pancreatic cells
32
RBCs use what pathways to metabolize glucose?
glycolysis or pentose phosphate pathway
33
in RBCs, what happens to lactate and CO2?
exit the cell because they are not phosphorylated.
34
what are the 5 key enzymes in glycolysis?
1. hexokinase/glucokinase
2. phosphofructokinase
3. glyceraldehyde-3P-dehydrogenase
4. phosphoglycerokinase
5. pyruvate kinase
35
What must be regenerated from NADH in order for glycolysis to proceed?
NAD+
36
Cells that have mitochondria can use O2 to regenerate NAD+ how?
by respiration
37
RBCs cannot use O2 for metabolism: why?
even though they are bathed in O2 they lack mitochondria
38
how do RBCs regenerate NAD+?
via lactate dehydrogenase (pyruvate --> lactate + NAD+)
39
RBCs constitutively form what from glucose?
lactate
40
when would muscle cells form lactate from glucose?
if deprived of O2
41
what does a kinase do in general?
phosphorylates a substrate
42
what do hexokinase/glucokinase do?
converts glucose into glucose-6P
43
how do the kinetic properties of hexokinase and glucokinase differ?
glucokinase in liver permits glucose uptake and glycogen synthesis at high blood glucose levels. glucokinase in pancreas functions as a blood glucose sensor. hexokinase reaches Vmax very quickly.
44
what happens to go from glucose-6P to fructose-6P? what enzyme catalyzes this reaction?
goes from an aldose to a ketose. enzyme = glucose phosphate isomerase.
45
what happens when fructose-6P goes to fructose-1,6-bisphosphate? what enzyme?
fructose-6P + ATP --> fructose-1,6-bisphosphate + ADP. enzyme is PFK-1. Not reversible. Main regulatory enzyme of glycolysis.
46
What activates PFK-1?
AMP, ADP, fructose-2,6-bisphosphate
47
What inhibits PFK-1?
ATP, citrate
48
How does glyceraldehyde-3P go to 1,3-bisphosphoglycerate? What enzyme/what is notable?
Enzyme is glyceraldehyde-3P dehydrogenase (GAPDH). Notable: the resulting molecule contains a high energy Acyl-P bond.
49
what will inhibit the GADPH reaction?
arsenate.
50
what enzyme catalyzes the reaction from 1,3-bisphosphoglycerate to 3-phosphoglycerate? what else results?
enzyme: phosphoglycerate kinase (named for reverse reaction). also yields ATP.
51
what enzyme catalyzes the reaction from phosphoenolpyruvate (PEP) to pyruvate? what else is produced?
enzyme: pyruvate kinase. also produces ATP.
52
what enzyme catalyzes the reaction from pyruvate to lactate? what else is produced?
lactate dehydrogenase (LDH). also produces NAD+ from NADH.
53
where does the equilibrium lie for the lactate dehydrogenase reaction?
far to the direction of lactate, which can then exit the cell.
54
what are the 2 isozymes of lactate?
H: occurs in heart. ideally suited to oxidize lactate (create pyruvate)
M: occurs in muscle, liver. ideal for reducing pyruvate (creating lactate)
55
how many ATPs are formed by glycolysis?
2 ATPs overall
56
what enzymes are the 3 main regulators of glycolysis?
1. hexokinase
2. PFK-1
3. pyruvate kinase
57
which reaches Vmax more quickly: hexokinase or glucokinase?
hexokinase. reaches Vmax very quickly.
58
what inhibits hexokinase? does this inhibit glucokinase?
glucose-6P. does not inhibit glucokinase.
59
how is glucose metabolism coupled to insulin secretion?
glucokinase is not inhibited by glucose-6P, so the rate of glycolysis in pancreatic beta-cells tracks with blood glucose levels. the more ATP formed in pancreatic beta cells by glycolysis --> K+ channel closes --> depol --> Ca2+ channel opens --> Ca2+ rushes in --> insulin released.
60
what enzyme catalyzes Fructose-6P to Fructose 2,6-bisphosphate?
PFK-2.
61
What is special about PFK-2?
it is a bifunctional enzyme: in one direction a kinase, the other is a phosphatase. catalyzes formation and degradation of Fructose 2,6-bisphosphate.
62
what would be the effect if both the kinase and the phosphatase of PFK-2 work simultaneously?
would generate heat in a futile cycle. hence these two need regulation so that they work at different times.
63
what enzyme cleaves Fructose 1,6P in half to form two 3C molecules?
aldolase
64
the conversion of glucose to 1,3 bisphosphoglycerate requires the investment of how many ATP/glucose?
2 ATP/glucose.
65
RBCs synthesize what from 1,3 bisphosphoglycerate?
both 3-phosphoglycerate (like other cells) and 2,3 bisphosphoglycerate (BPG) which decreases oxygen affinity of hemoglobin.
66
What inhibits pyruvate kinase?
ATP. this is impt in skeletal muscle.
67
What are the 3 enzymes in glycolysis that exist as different isozymes?
1. hexokinase/glucokinase
2. pyruvate kinase
3. lactate dehydrogenase
68
what activates pyruvate kinase in the liver?
liver isozyme of pyruvate kinase is activated by Fructose-1,6-P
69
What favors the formation of lactate from pyruvate in cells?
the exit of the product (lactate) from the cell, and the large negative free energy of the reaction.
70
how many different isozymes are there for lactate dehydrogenase?
there are 5.
71
what is the clinical significance of having an LDH isozyme that is specific to heart muscle?
to diagnose an MCI, can draw blood and test for the H4 (heart-specific) LDH isozyme.
72
in the absence of O2, what regenerates NAD and allows glycolysis to proceed?
LDH and the pyruvate -> lactate reaction.
73
Lactose is what 2 monosaccharides?
galactose + glucose
74
Sucrose is what 2 monosaccharides?
glucose + fructose
75
Maltose is what 2 monosaccharides?
2 glucose
76
What is lactose intolerance?
an acquired deficiency of lactase
77
what is galactosemia?
loss of uridyl transferase enzyme, causing galactol to accumulate
78
what is fructose intolerance?
loss of liver-specific aldolase causing Fructose-1P to accumulate
79
what is the most common enzymopathy?
G6PDH
80
what do most G6PDH individuals experience?
usually asx
81
what are the most common manifestations of G6PDH deficiency?
adult: hemolytic anemia
neonatal: jaundice
82
what is the first enzyme in the pentose phosphate pathway?
G6PDH
83
what is the importance of the first part of the pentose phosphate pathway/G6PDH?
forms NADPH
84
why is NADPH important?
required to generate reduced glutathione (which protects RBCs against oxidative damage)
85
what does the pentose phosphate pw form (3 things)?
ATP, pentoses, NADPH
86
what can pentoses be converted to that is part of the glycolytic and gluconeogenic pws?
glyceraldehyde-3P
87
what 2 things can glyceraldehyde-3P be converted to?
1. glucose
| 2. lactate (via glycolysis)
88
what is the only source of NAPDH in RBCs?
pentose phosphate pw
89
can RBCs that are G6PDH deficient form ribose?
yes, the pentose reactions are reversible
90
what tissues have high amounts of pentose phosphate pw activity?
adipose, liver, lactating mammary, adrenal cortex, thyroid, testis, RBCs
91
what tissues have LOW amounts of pentose phosphate pw activity?
heart, skeletal muscle
92
how are disaccharides converted to monosaccharides?
by enzymes on the surface of intestinal mucosal cells
93
what causes fructose intolerance?
loss of liver-specific form of aldolase, which results in accumulation of Fructose-1P and depletion of ATP in liver cells
94
what causes galactosemia?
the loss of a Galactose-1P uridyl transferase
95
G6PDH deficiency results in the lack of what in RBCs?
NADPH and therefore glutathione reductase and therefore glutathione.
96
Anabolic (constructive) pathways usually use what as a cofactor?
NADPH
97
Catabolic (breakdown) pathways usually use what as a cofactor?
NAD+
98
In the course of forming Ribose-5P, is NADPH created? ATP?
NADPH: Yes
ATP: No
99
In the course of forming pentoses into glucose-6P, is NADPH created? ATP?
NADPH: Yes??
ATP: No
100
The pentose phosphate pw is linked to glycolysis via what enzyme reactions?
transketolase and transaldolase
101
In the course of forming pentoses to lactate via glycolysis, is NADPH created? ATP?
NADPH: Yes
ATP: Yes
102
where is most fructose metabolized?
liver
103
what does accumulation of Fructose-1P cause?
liver damage; depletion of P (and depletion of ATP); inhibition of glycogen phosphorylase (which catalyzes glycogen -> glucose-1P); hypoglycemia (because liver glycogen cannot be used to replace blood glucose)
104
name 4 symptoms of lactose intolerance
1. abdominal discomfort, cramps
2. bloating
3. increased urination (trying to release stomach contents)
4. diarrhea
105
What is the role of glutathione in RBCs?
protects from oxidative damage
106
what is the result of oxidative damage in RBCs?
hemolysis --> anemia.
107
What are Heinz bodies?
inclusions in RBCs comprised of denatured hemoglobin (could be due to oxidative damage)
108
why does G6PDH deficiency only affect RBCs?
Other cells have alternate means/enzymes of forming NADPH.
109
define gluconeogenesis
the synthesis of glucose from precursors other than glycogen
110
where does gluconeogenesis primarily occur?
LIVER, sometimes kidney
111
what does pyruvate dehydrogenase do?
converts pyruvate to Acetyl CoA and CO2 in the mitochondria.
112
What does pyruvate dehydrogenase use as cofactors? (5 things)
TPP, Lipoic Acid, FAD, NAD, Coenzyme A
113
what is pyruvate dehydrogenase's composition?
composed of 3 enzymes (E1, E2, E3)
114
3 fates of pyruvate, and the enzymes that catalyze those reactions?
1. lactate (lactate dehydrogenase)
2. CO2 and Acetyl CoA (pyruvate dehydrogenase)
3. oxaloacetate (pyruvate carboxylase)
115
What is the point of gluconeogenesis?
replenish blood glucose for use by the brain (cannot use Fatty Acids)
116
name 3 carbon sources for gluconeogenesis
1. lactate (from RBCs and exercising muscle)
2. some Amino Acids (from muscle protein)
3. Glycerol (from triglycerides)
117
What are the 3 enzymes that are used for glycolysis but are sidestepped for gluconeogenesis?
1. pyruvate kinase (oxaloacetate circle)
2. PFK-1 (Fructose-1,6-bisphosphatase)
3. hexokinase/glucokinase (glucose-6-phosphatase)
118
how much energy is used to convert pyruvate to PEP?
2 high-energy intermediates: 1 ATP, 1 GTP
119
pyruvate carboxylase is located where?
mitochondria
120
pyruvate carboxylase requires what to activate it, and what as a cofactor?
Acetyl-CoA activates it, and Biotin is a cofactor
121
PEP carboxykinase is located where?
cytoplasm
122
why does oxaloacetate need to be transformed to malate?
oxaloacetate cannot cross the mito membrane, but malate can. once malate has crossed out, it is changed back to oxaloacetate.
123
what mitochondrial conditions favor gluconeogenesis?
high NADH
124
What inhibits Fructose-1,6-bisphosphatase?
Fructose-1,6-bisphosphate and ADP
125
What activates Fructose-1,6-bisphosphatase?
Citrate and ATP
126
what both activates Fructose-1,6-bisphosphatase AND inhibits PFK-1?
Citrate and ATP
127
What conditions will favor gluconeogenesis and slow down glycolysis?
1. High ATP levels will do both
| 2. High blood lactate/high mitochondrial NADH will favor gluconeogenesis.
128
Why do we need to transform Glucose-6P to glucose during gluconeogenesis?
Glucose-6P cannot exit the cell.
129
what organs have Glucose-6-Phosphatase?
Liver and kidney, but NOT muscle
130
Where does the Cori Cycle take place? what happens?
in Liver. Takes up blood lactate (formed by exercising muscle) and converts it to blood glucose for use by brain.
131
what 3 reactions/enzymes require ATP in gluconeogenesis?
1. pyruvate carboxylase
2. PEP carboxykinase
3. 3-Phosphoglycerate kinase
132
Gluconeogenesis from lactate requires how many ATP per glucose?
6
133
why is the pyruvate dehydrogenase reaction irreversible?
because CO2 leaves, and because there is a large negative free energy.
134
Deficiency of the E1 subunit of PDH is the most common cause of what?
genetic lactic acidosis
135
What is the order in which the cofactors are used in the Pyruvate Dehydrogenase reaction? What part swings?
TPP, Lipoic Acid, Coenzyme A, FAD, NAD. It is the Lipoic Acid/Lysine that swings from E2 that accepts part of the complex formed by TPP.
136
How is PDH regulated?
There is a protein kinase (inhibitory) and a protein phosphatase (activating) that regulate PDH
137
What inhibits/activates the protein kinase which inhibits PDH?
Inhibits: Pyruvate and ADP
Activates: ATP, acetyl CoA, NADH
138
What inhibits/activates the protein phosphatase that activates PDH?
Inhibits: nothing
Activates: calclum, insulin
139
quantitatively, what is the most impt precursor for gluconeogenesis?
lactate
140
how is pyruvate converted to PEP?
enzymes: pyruvate carboxylase and PEP carboxykinase. Oxaloacetate --> malate --> Oxaloacetate.
141
why can't pyruvate be converted directly back to PEP?
the pyruvate kinase reaction is irreversible
142
What is Von Gierke's disease?
Type I storage disease due to the genetic loss of glucose-6Pase.
143
Where is most glycogen stored?
muscle and liver
144
what does muscle glycogen provide? what does it not provide?
provides Glucose-6P for muscle. NOT a source of blood glucose
145
liver glycogen can be a source of what?
blood glucose
146
the glycogen polymer overall is attached to a small protein called what?
glycogenin
147
what are the 3 enzymes the synthesizes glycogen from glucose-1P?
1. UDP-glucose pyrophosphorylase
2. Glycogen synthase
3. branching enzyme
148
what are the 2 enzymes that degrade glycogen to glucose-1P?
1. glycogen phosphorylase
| 2. debranching enzyme
149
what are the regulated enzymes in the synthesis/degradation of glycogen?
glycogen phorphorylase and glycogen synthase
150
why is muscle not a source of blood glucose?
does not contain glucose-6-phosphatase to convert glucose-6P to glucose -> bloodstream
151
what are the 2 types of glycosidic bonds in glycogen?
1. alpha-1,6 glycosidic linkage (branches)
| 2. alpha-1,4 glycosidic linkage (straight)
152
what is the non-reducing end? what characterizes the reducing end?
the end that monosaccharides will be added to. the reducing end is connected to glycogenin
153
why is it helpful to store glucose as glycogen?
less change to osmotic pressure of cell
154
what is one difference between glycogen and fat?
glycogen can be metabolized and provide energy in the absence of oxygen
155
what enzyme catalyzes Glucose-1P to Glucose-6P and back?
phosphoglucomutase
156
UDP-glucose pyrophosphorylase does what?
Glucose-1P to UDP-glucose (which can be added to glycogen)
157
glycogen synthase does what?
adds units of UDP-glucose to glycogen chains with alpha-1,4 linkages.
158
what activates/inhibits glycogen synthase?
activates: dephosphorylation by protein phosphatase. inhibits: phorphorylation by a protein kinase
159
what is the function of the branching enzyme?
transfers 7 or more glucosyl residues from the non-reducing end, leaving at least 4 behind as a primer. forms an alpha-1-6 glycosidic bond
160
what does glycogen phosphorylase do?
breaks alpha-1,4 bonds of glycogen. yields single glucose-1P, trapped in cell
161
what activates/inhibits glycogen phosphorylase?
activates: phosphorylation by protein kinase. inhibits: dephos by protein phosphatase
162
what does the debranching enzyme do?
Bifunctional enzyme: 2 activities in one protein. once branches are shortened to 4 residues by glycogen phosphorylase, transfers 3 units to non-reducing end. Then breaks alpha-1.6 bond and liberates the final residue of glucose-1P
163
where is glucose-6-phosphatase found? what does it do?
ER of liver cells. hydrolyzes Glucose-6P to glucose + free phosphate. Glucose then transported out of cell to cytoplasm.
164
what is the limit dextran?
a short stretch of glucosyl residues connected to the glycogenin protein, that glycogen synthase adds further units to to form glycogen.
165
glycogen synthesis and degradation: regulated the same way in muscle and liver or differently?
differently: in muscle, regulated based on energy status. in liver, regulated based on glucose availability (ie nutritional status)
166
the protein kinase cascade that regulates phosphorylation/dephosphorylation of glycogen phosphorylase and glycogen synthase is controlled by what?
cAMP (in both muscle and liver)
167
what permits rapid changes in muscle glycogen metabolism?
Ca transients
168
what regulates liver glycogen metabolism?
glucose levels
169
overall, what does glycogen synthase do?
regulates glycogen synthesis
170
overall what does glycogen phosphorylase do?
regulates glycogen degradation
171
what does glucose do to glycogen synthase in the liver?
activates it
172
what does AMP do to glycogen phosphorylase in the muscle?
activates it
173
what does glucose-6P do to glycogen phosphorylase in the muscle?
inhibits it (via blocking AMP activation)
174
which is phosphorylated, glycogen phosphorylase a or b?
a
175
which is active primarily in muscle, glycogen phosphorylase a or b?
b
176
which is active primarily in liver, glycogen phosphorylase a or b?
a
177
which indicates active state of glycogen phosphorylase, T or R?
R (relaxed) state. T = tight state.
178
what does glycogen phosphorylase kinase do?
phosphorylases glycogen phosphorylase using ATP as a source of phosphate. b = unphos, a = phos. think b = bare.
179
in muscle, glycogen phosphorylase b is activated by what?
AMP
180
in muscle, glycogen phosphorylase b is inhibited by what?
ATP, glucose-6P
181
in liver, glycogen phosphorylase a is activated by what?
not sure
182
in liver, glycogen phosphorylase a is inhibited by what?
glucose (transforms it to the T state)
183
even in the presence of oxygen, do cancer cells do glycolysis?
yes, this is termed aerobic glycolysis. produces large amounts of lactate
184
how can we see whether tumors are taking up large amounts of glucose?
via PET scanning: basically labeled glucose that is detected (18-F-fluorodeoxyglucose)
185
how do cancer cells gain growth advantage by relying on glycolysis?
1. ability to grow in hypoxic environments
| 2. good rates of synthesis of key metabolic intermediates for biosynthesis and growth regulation
186
what is PKM2?
isozyme of pyruvate kinase in cancer cells. slows rate of glycolysis, allowing the accumulation of metabolic intermediates that are used for cell growth
187
what is IDH1?
isocitrate dehydrogenase isozyme in CYTOPLASM (usually part of the citric acid cycle in mito). MUTATED IDH1 produces 2HG, which may affect tumor growth (not sure exactly, but measuring this is a useful way to detect cancer).
188
how many ATP from glucose are obtained via glycolysis?
net 2/glucose
189
what might be the advantages of using glycolysis to lactate (and not CAC) for cancer cells?
1. simple pathway
2. ATP needed for cell division/growth is less than that for cell maintenance
3. the malate-aspartate shuttle might be saturated at higher rates of CAC?, so pyruvate -> lactate ensures steady rate of NAD regeneration.
4. ability to grow in hypoxic environments and provide lactate to non-hypoxic cells
190
what is LDH-A?
LDH isozyme that favors pyruvate -> lactate
191
what happens to the activity of pyruvate dehydrogenase in cancer cells?
decreased activity, due to phosphorylation by a protein kinase (PDK)
192
what controls the expression of LDH-A and PDK genes (cancer cells)?
transcription factor called HIF-1alpha. upregulated in cancer cells
193
what is VHL?
tumor suppressor gene. normally binds to HIF-1alpha and leads to proteosomal destruction of HIF-1alpha. but VHL is inactivated in cancer phenotpyes leading to increased HIF-1alpha expr.
194
increased HIF-1alpha expr leads to what?
upregulated LDH-A and PDK
195
what is PKM2?
isozyme of pyruvate kinase. prevalent in cancer phenotypes. relatively slow isozyme: effect = slow glycolysis overall (slow PEP -> pyruvate) to allow accumulation of upstream intermediates needed for growth
196
What is VHL?
Von Hippel-Lindau, a tumor suppressor gene. If mutated, will allow HIF-1a to proliferate. HIF-1a upregulates PDK and LDH-A
197
what determines the fate of pyruvate?
NADH/NAD ratio
