Section 2 Flashcards
1
Q
What important biochemical intermediate serves to link various metabolic pathways in the cell?
A
Acetyl-CoA
2
Q
Acetyl-CoA can be formed from what?
A
Carbs, fatty acids, and amino acids from proteins
3
Q
What is a substrate for the citric acid cycle and a metabolic precursor for the formation of fatty acids, ketone bodies and cholesterol?
A
Acetyl-CoA
4
Q
What is the PDH complex?
A
pyruvate dehydrogenase complex is a multi-enzyme complex that catalyzes the conversion of pyruvate to acetyl-CoA
5
Q
Where is PDH found?
A
mitchondrial matrix
6
Q
Where is pyruvate generated?
A
in the cytosol by glycolysis
7
Q
How does pyruvate get into the mitochondrial matrix?
A
diffuses freely through the outer membrane and via a translocase located in the inner membrane
8
Q
What are the three enzyme subunits that make up PDH?
A
Ena: pyruvate decarboxylase
Enb: dihydrolipoyl transacetylases
Enc: dihydrolipoyl dehydrogenase
9
Q
What are the 5 coenzymes that is required by PDH complex?
A
2 soluble: CoA and NAD+
3 tightly bound to enzyme subunits: TPP, lipoamide, and FAD
10
Q
What are the 4 vitamins involved as part of coenzyme structures?
A
B1: Thiamin (TPP)
B2: Riboflavin (FAD)
B3: Niacin (NAD+/NADH)
B5: Panthothenic acid (CoASH)
11
Q
What is the substrate for PDH?
A
pyruvate
12
Q
What are all the products of PDH?
A
acetyl-CoA, NADH, CO2
13
Q
What are the two mechanisms involved in the regulation of PDH?
A
end-product inhibition and phosphorylation/dephosphorylation
14
Q
Explain the activity of PDH complex when it is in the phosphorylated state.
A
less active
15
Q
Explain the activity of PDH complex when it is in the dephosphorylated state.
A
more active
16
Q
What enzymes regulate the phosphorylation of PDH?
A
PDH Kinase and PDH Phosphatase
17
Q
What is the function of PDH Kinase when it is active?
A
phosphorylates PDH thus inhibiting its activity
18
Q
What activates PDH Kinase?
A
acetyl-CoA and NADH
19
Q
What inhibits PDH Kinase?
A
pyruvate, NAD+, CoASH and ADP
20
Q
What are the two main roles of CAC?
A
1) produce reduced electron carriers (NADH and FADH2) to be oxidized by ETS
2) metabolic precursors for biosynthesis
21
Q
Where does the CAC occur?
A
mitochondrial matrix
22
Q
Which cells do not have mitochondria?
A
RBCs
23
Q
What is the fuel for CAC?
A
acetyl-CoA
24
Q
What are the products of CAC?
A
OAA, 2CO2, 3NADH, GTP, and FADH2
25
Which reactions of CAC give off CO2?
Isocitrate Dehydronase (isocitrate to alpha-ketoglutarate), alpha-KGDH (alpha-KG to succinyl-CoA)
26
Which reactions of CAC produce NADH?
isocitrate dehydrogenase, alpha-KGDH, malate dehydrognase
27
Which reactions of CAC produce FADH2?
succinate dehydrogenase (succinate to fumarate)
28
Which reaction of CAC involves substrate-level phosphorylation?
succinyl-CoA +GDP+Pi to succinate+GTP
29
How many ATPs (or ATP-equivalents) are produced in the CAC from one molecule of acetyl-CoA?
12 ATPs: 3 for each NADH (9), 2 for FADH2 (2) and 1 GTP
30
How many ATPs are produced in the CAC from one molecule of pyruvate?
15 ATPs (1 NADH produced from PDH)
31
How many ATPs are produced in the CAC from one molecule of glucose
30 ATPs
32
What is the most important anaplerotic enzyme?
pyruvate carboxylase
33
Where is pyruvate carboxylase located?
mitochondrial matrix
34
What reaction does pyruvate carboxylase catalyze?
the formation of OAA from pyruvate, ATP, and CO2
35
Pyruvate carboxylase is allosterically activated by what?
acetyl-CoA (more acetyl-CoA, more OAA needed to condense to citrate)
36
What vitamin is required by pyruvate carboxylase?
B vitamin: Biotin
37
What is the importance of anaplerotic enzymes?
they replenish the supply of OAA to keep the CAC operational (also the first step in gluconeogenesis)
38
What are the two most important enzymes for regulation of CAC?
isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase
39
What activates isocitrate dehydrogenase?
ADP
40
What inhibits isocitrate dehydronase?
NADH
41
What inhibits alpha-KGDH?
succinyl-CoA (product inhibition) and NADH (cell has enough ATP)
42
What are the consequences of having diminished PDH activity?
there will be a backup of pyruvate produced from glycolysis, which will be converted to lactate by lactate dehydrogenase, causing serum lactic acidemia
43
Defects in any of the PDH enzyme subunits can cause what condition in infants and young children?
chronic lactic acidosis. diminished PDH activity causes diminished ATP production, thus affecting the CNS. these patients will often present with severe neurological problems
44
In the reaction catalyzed by lactate dehydrogenase, what is used as the electron donor?
NADH
45
What causes Beri-Beri?
severe dietary deficiency of vit. B1, thiamin, which is required by both PDH and alpha-KGDH
46
What is a characteristic symptom of thiamin deficiency?
neuromuscular involvement
47
Which populations are more susceptible to thiamin deficiency?
eldery, low-income and alcoholics (due to poor diets)
48
Would a thiamin deficiency affect RBCs? Why or why not?
No, because RBCs do not have PDH or alpha-KGDH
49
What are other sources of acetyl-CoA, other than pyruvate?
large amount of acetyl-CoA can be supplied by fatty acid degradation
50
What happens when too much acetyl-CoA is produced by the liver?
"overflow" of acetyl-CoA gets converted to ketone bodies by the liver
51
When does the conversion of acetyl-CoA from fatty acid degradation occur?
during fasting state and in uncontrolled type 1 diabetes
52
What are the three major ketone bodies produced from excess fatty acids?
acetoacetate, beta-hydroxybutyrate, and acetone
53
How can ketone bodies be utilized for ATP generation, especially in the brain?
ketone bodies >> acetyl-CoA >> ETS
54
What happens when production of ketone bodies become too great?
Lead to ketoacidosis, can lead to coma and death in diabetic patients with uncontrolled type 1 diabietes
55
What is the function of the mitochondrion?
major ATP-generating organelle of the cell
56
What is a characteristic of the inner mitochondrial membrane?
highly invaginated to increase surface area
57
What is the space between the inner and outer mitochondrial membranes called?
periplasmic space
58
What is the most inner compartment of the mitochondrion called?
mitochondrial matrix
59
Compare and contrast the outer and inner mitochondrial membrane.
the outer membrane is rather porous and is permeable to metabolites generated in metabolic pathways such as pyruvate.
the inner membrane is relatively impermeable and has specific translocase proteins to transport molecules in and out.
60
What soluble enzyme systems are located in the mitochondrial matrix?
PDH complex, enzymes for FA beta-oxidation, some enzymes for the urea cycle, and CAC enzymes (except succinate dehydrogenase)
61
Where is the ETS located?
the chain of electron carriers are embedded in the inner membrane
62
What is the function of ETS?
they funnel electrons from reduced substrates (NADH and succinate) to molecular oxygen (final electron acceptor) to form water and the process is coupled with substrate-level phosphorylation to generate ATP.
63
What is the chemical nature of the electron carriers in ETS?
most of the electron carriers of ETS are proteins with the exception of ubiquinone or CoQ, a lipid carrier
64
What are the types of proteins in the ETS?
dehydrogenases and iron-containing proteins
65
What coenzymes are in dehydrogenases of ETS?
FAD or FMN, which are reduced to FADH2 and FMNH2, respectively
66
What are the two types of iron-containing proteins?
heme-iron proteins (cytochromes) and nonheme-iron proteins (iron-sulfur proteins)
67
What are the major reduced substrates of ETS? What is the metabolic pathway is the major generator of these substrates?
NADH and succinate. CAC
68
What is the first complex of ETS? What is oxidized and what is reduced?
NADH-CoQ Reductase
69
What is the coenzyme in complex I?
FMN
70
What is oxidized and reduced in complex I?
NADH is oxidized to NAD+ and CoQ is reduced to CoQH2
71
What are the substrates and products of complex I?
Substrates: NADH, H+, CoQ
Products: NAD+, CoQH2
72
What is the second complex of ETS?
Succinate-CoQ Reductase
73
What is the conenzyme in complex II?
FAD
74
What is oxidized and reduced in complex II?
succinate is oxidized to fumarate and CoQ is reduced to CoQH2
75
What are the substrates and products of complex II?
substrates: succinate, CoQ
products: fumarate, CoQH2
76
What is the third complex of ETS?
CoQH2-Cytochrome c Reductase
77
What is oxidized and reduced in complex III?
CoQH2 is oxidized to CoQ and the iron group of cytochrome c is reduced from Fe3+ to Fe2+
78
What are substrates and products of complex III?
substrates: CoQH2, 2 Cyt. c (Fe3+)
products: CoQ, 2 Cyt. c(Fe2+), 2H+
79
What is the fourth complex of ETS?
Cytochrome c oxidase
80
What is oxidized and reduced in complex IV?
cytochrome c is oxidized (Fe2+ to F23+) and oxygen is reduced to make water
81
What are the substrates and products of complex IV?
substrates: 4 Cyt. c (Fe2+), 4H+, O2
products: 4 Cyt. c (Fe3+), 2H2O
82
Explain the chemical nature of coenzyme Q
It is the only non-protein electron carrier in the ETS. It is a hydrophobic benzoquinone that can be reduced stepwise. The hydrophobic nature of CoQ allows it to dissolve in and freely diffuse within the lipid bilayer.
83
What is the function of coenzyme Q?
CoQ serves as a mobile carrier in the bilayer and shuttles reducing equivalents from the various dehydrogenase complexes to complex III.
84
What is the sequence of electron flow through the carriers of ETS?
electron flow starts either complex I or II, then it continues to complex III and then to IV to ultimately make water
85
What is the function of cytochrome c?
it serves as a mobile carrier that shuttles reducing equivalents between complexes III and IV
86
What are the proton pumps of ETS?
Complex I, III, and IV
87
What is the prosthetic group of cytochromes?
heme iron
88
How many ATPs can be formed from the oxidation of NADH?
3
89
How many ATPs can be formed from the oxidation of succinate or FADH2?
2
90
Which complexes are sites where enough free-energy is released to form ATP? Which are not
Complex I, III, and IV all have enough free-energy to generate ATP. Complex II does not.
91
What is the purpose of pumping protons out of the mitochondrial complex?
to create an electrochemical gradient across the inner membrane as a store of free-energy
92
Which is more positive? periplasmic space or mitochondrial matrix?
periplasmic space
93
How is the store of free-energy liberated in the ETS?
by the electron flow through the ETS to molecular oxygen. the energy is trapped to drive the formation of ATP production
94
What is the purpose of ATP synthase complex and where is it located?
it is located in the inner mitochondrial membrane and it couples the re-entry of protons to the synthesis of ATP.
95
What is the role of F0 portion of the ATP synthase complex and where is it located?
The F0 unit is a multi-subunit transmembrane protein that forms a proton channel through the inner membrane.
96
What is the role of F1 portion of ATP synthase complex and where is it located?
The F1 unit is also a multi-subunit structure and it is located within the matrix. It is the unit that contains the catalytic activity for the actual synthesis of ATP from ADP + Pi.
97
What is the effect of cyanide on oxidative phosphorylation?
CN- is an inhibitor of complex IV, cytochrome oxidase. It inhibits reduction of oxygen to water by reacting with the heme group, causing the electron flow to come to a stop.This results in lactic acidosis and death can occur from respiratory arrest.
98
What is the effect of carbon monoxide on oxidative phosphorylation?
it is an inhibitor of complex IV, cytochrome oxidase. CO binds to Hb because it has a higher affinity for it then O2, thus O2 can't be delivered to tissues. This ultimately leads to lack of terminal electron acceptor. Lactic acidosis will occur and the high concentration of CO bound to Hb causes the blood to take on a cherry red color.
99
What is the treatment for CO poisoning?
100% oxygen or a hyperbaric chamber. These treatments both increase the amount of oxygen dissolved in plasma so that more is delivered to the tissues for reduction by the ETS and also hasten displacement of CO from the Hb iron.
100
How does ATP get from the mitochondrion to the cytoplasm?
Adenine nucleotide translocase is located in the inner membrane and exchanges ATP for ADP. This is how the mitochondria gets ADP to be re-phosphorylated to ATP.
101
What is the action of atractyloside?
Inhibitor of adenine nucleotide translocase, effectively inhibiting the ATP from being transported out of the mitochondrion.
102
What are uncoupling proteins?
uncouplers of oxidative phosphorylation inhibits the formation of ATP, but the electron flow still occurs. It is an alternate route for the re-entry of protons by by-passing the ATP synthase. The potential energy is lost as heat. (great for hibernating animals)
103
What's an example of an uncoupler?
DNP (2,4-dinitrophenol)
104
How is DNP imported into the mitochondria and how does it work?
DNP is a negatively charged molecule. As DNP approaches the mitochondria, it gets protonated due to the excessive H+ ions. This protonation makes the molecule uncharged and more hydrophobic, allowing it the enter the inner membrane. It partitions by mass action and enters the matrix, where it will get deprotonated. Thus, DNP acts as an alternate route for protons to enter the matrix, bypassing the ATP synthase. As a result, the free-energy is lost as heat.
105
How does a defect in any of the complexes of ETS cause a serum lactic acidosis?
It will interrupt the electron flow within the ETS. This means the cell is unable to oxidize pyruvate by CAC and ETS. The pyruvate is then converted to lactate
106
What is DNP poisoning?
DNP derivatives are effective as herbicides. Human exposure leads to hyperthermia due to the uncoupling of oxidative phosphorylation
107
Why is an adequate supply of oxygen important to cells?
oxygen is used as the terminal electron acceptor in the ETS to make water. An adequate amount of oxygen is needed for optimal ATP production
108
What is the treatment for cyanide poisoning?
It must be rapid. Nitrites are administered by inhalation and injection to get the cyanide to release from the oxidase and to bind to Hb instead. Another treation is administration of sodium thiosulfate, which leads to conversion of cyanide to the non-toxic derivative thiocyanate, SCN-
109
LHON, MERRF, and MELAS are examples of what kind of disorders?
mutations in the mitochondrial genome, leading to defects in oxidative phosphorylation
110
What is the significance of carbohydrates?
it is the primary energy source, modifiers of proteins and hormones, and part of nucleic acids
111
What is the basic formula for carbohydrates?
C(H20)n
112
Describe the chemistry nature of glucose
Each carbon is linked to one hydroxyl group, with the exception of the double bond on C1 found in the linear structure.
113
When the hydroxyl group of C1 is on the same side of C6, what is this configuration called?
beta-configuration
114
When the hydroxyl group of C1 is on the opposite side of C6, what is this configuration called?
alpha-configuration
115
The interconversion between alpha and beta configuration of glucose is called what?
mutarotation
116
Why is the reducing power of glucose damaging?
formation of early glycosylation products that undergo slow changes through the action of reaction oxygen to form advanced glycation endproducts (AGEs).
117
How do early glycosylation products form?
In the open chain form, sugars can reduce proteins. The sugar forms a covalent bond with amino acids on the surface of proteins, forming early glycosylation products
118
What is the significance of AGEs?
they are potentially dangerous to tissues, as they modify extracellular protein structures
119
What is HbA1c?
glycation of Hb
120
How is HbA1c formed?
When glucose level is chronically high, nonenzymatic, spontaneous glycation of Hb will occur.
121
What is the clinical significance of HbA1c?
This form of Hb is the tell-tale sign for individuals with diabletes. Note that RBCs' life span is 120 days. This allows clinicians insight on the management of blood sugar of diabetic patients
122
What does oxidation of glucose yield?
acids (uronic acids) and ketones (lactone). Note that hydrolysis of gluconolactone initiaties PPP
123
What does reduction of glucose yield?
hexitol (sorbitol and inositol)
124
When does glucose get phosphorylated?
upon entry into the cell, by either glucokinase (in the liver) and hexokinase (all other cells)
125
Where are free glucose found?
extracellular fluids and enterocytes
126
How will you find glucose in a cell?
glucose-6-phosphate. there is no free glucose in a cell
127
Glucosamine synthesis starts with what molecule?
fructose-6-phosphate
128
Where do you find sulfated sugars?
large proteglycans that make up extracellular matrix
129
Where on sugars can sulfation occur?
it can occur in different positions of the ring and in more than one position. sulfate groups add negative charges
130
What is aspartame and how is it metabolized?
it is often used as a artificial sweetner. it is not a sugar and it is metabolized to amino acids, phenylalanine and aspartic acid
131
What is saccharine and how is it metabolized?
saccharine is not a sugar and cannot be metabolized. It is excreted by urine
132
What is sucralose (Splenda) and how is it metabolized?
it is polychlorinated sucrose. It is not metabolized and has no effect on insulin secretion
133
What is the chemical makeup of maltose?
2 molecules of glucose via alpha linkage (1,4)
134
What is the chemical makeup of lactose?
1 galactose and 1 glucose via beta linkage (1,4)
135
What is the chemcial makeup of sucrose?
1 glucose and 1 fructose via alpha linkage
136
What is the purpose of activation of glucose?
to prevent glucose from being degraded, it has to be linked to a nucleotide. this prepares the sugar for the formation of glycosidic bonds
137
What occurs in the first step of activation of sugars?
the sugar is linked to a nucleotide (usually a sugar phosphate reacting with a nucleotide triphosphate) and requires the input of energy
138
What occurs in the second step of activation of sugars?
the activated sugar nucleotide then transfers the carbohydrate to the target molecule and it is catalyzed by glycosyltransferases. This step does not require the input of energy
139
How are glycosidic bonds formed?
between a substrate and an activated sugar nucleotide that already contains the energy necessary to form the bond.
140
What activated sugar is required for synthesis of glycogen?
UDP-glucose
141
What activated sugar is required for liver detoxification reactions?
UDP-glucuronic acid
142
Describe the structures of glycogen and amylopectin
linear storage polymer of alpha (1,4) glucose chains branch with alpha (1,6)- glycosidic bonds. glycogen has higher degree of branching than amylopectin. amylopectin is used in plants
143
Describe the structure of amylose
linear storage polymer of alpha (1,4) glucose monomers
144
Describe the structure of cellulose
beta- linkages between glucose monomers. humans cannot break down beta linkages
145
What the difference between alpha-linked and beta-linked polysaccharides?
alpha-linked is for energy storage and can be broken down.
| beta-linked is for structural support and cannot be digested.
146
Starch and glycogen degradation is initiated by what enzyme?
alpha-amylase
147
Where is alpha-amylase found?
saliva and pancreatic secretions
148
What is the function of alpha-amylase?
cleaves alpha-glycosidic bonds randomly in the middle of the molecule
149
What are the main breakdown products from alpha-amylase?
disaccharides maltose and trisaccharide maltotriose. there are also glucose and alpha-limit dextrin fragments generated
150
What enzymes further degrade the disaccharides and tri-saccharides in the small intestine?
alpha-glucosidase and isomaltase
151
What enzyme breaks down maltose and into what?
maltase hydrolyzes maltose into two glucose molecules
152
What enzyme breaks down lactose and into what?
lactase hydrolyzes lactose into glucose and galactose
153
What enzyme breaks down sucrose and into what/?
sucrase/isomaltase complex splits sucrose into gucose and fructose
154
Polysaccharides must be broken down into what before they can be taken up?
monosaccharides
155
What is lactose intolerance?
occurs when humans have a malfunction in lactase that results in an inability to cleave lactose into galactose and glucose. the lactose cannot be broken down so it remains the intestines and causes influx of water resulting in diarrhea. lactose is readily digested by bacteria in the intestinal flora and the by-product is hydrogen and methane gas
156
What is raffinose?
sugar abundant in leduminous seeds and cannon be digested by humans but it does get digested by bacteria and it produces gaseous byproducts
157
Monosaccharides from the diet are taken up by what type of cells?
epithelial cells of the small intestine
158
What is the function of Na+/glucose symporter?
transports glucose against the concentration gradient into the epithelial cells from the intestinal lumen (secondary active transport)
159
Where are glucose and galactose are taken up to by active transport?
intestinal epithelium from intestinal lumen
160
Where are glucose and galactose are released to by facilitated diffusion?
circulation from intestinal epithelium
161
Which has a higher concentration of glucose, ECF or intestinal epithelium?
intestinal epithelium
162
What is the function of GLUT2 and where is it found?
intestine: release of glucose/galactose from epithelial cells into circulation (facilitated diffusion)
- also found in liver and pancreas
163
Once glucose enters the circulation, what happens to it?
taken up by cells via facilitate diffusion via either GLUT1 or GLUT3
164
What happens to glucose once it enters the cell?
gets phosphorylated (there's no free glucose)
165
Glucose can also enter the liver via what transporter?
GLUT2
166
Through what transporter does fructose enter from the intestinal lumen?
GLUT5
167
What happens to fructose after it enters the intestinal epithelium?
it diffuses across epithelium and into circulation and then into the liver where it will get phosphorylated
168
What charge does glucose-6-phosphate carry and what is its significance?
negative, it can't cross the cell membrane
169
What is the function of glucokinase and where is it found?
phosphorylates C6 of glucose in liver
170
What is the function of hexokinase and where is it found?
same as glucokinase (phosphorylates glucose) and it's in all cells
171
What is the significant difference between glucokinase and hexokinase besides location?
hexokinase is inhibited by its product, glucose-6-phosphate, glucokinase is not
172
What does glucose get converted to in glycolysis?
2 pyruvate
2 ATP
1 NADH
173
Where does glycolysis occur?
cytoplasm
174
Is glycolysis aerobic or anaerobic?
anaerobic
175
What are the two ways fructose can be metabolized?
1) by the liver (first step by fructokinase)
| 2) slowly by muscles via hexokinase
176
What does fructose get converted to by fructokinase?
fructose-1-phosphate
177
How does galactose get metabolized?
must be converted to glucose first
178
What are the regulation points of glycolysis?
hexokinase
phosphofructokinase
pyruvate kinase
179
What is the rate limiting step of glycolysis?
phosphofructokinase
180
What stimulates hexokinase?
insulin
181
What inhibits hexokinase?
G6P and acetyl CoA
182
What stimulates phosphofructokinase?
fructose-2,6-bisphosphate (stimulated by hormones)
183
What inhibits phosphofructokinase?
ATP and citrate
184
What stimulates pyruvate kinase?
fructose-1,6-bisphosphate
| insulin
185
What inhibits pyruvate kinase?
ATP
186
Which enzymes of glycolysis require energy?
hexokinase (glucokinase)
| phosphofructokinase
187
What enzymes of glycolysis yield energy?
glyceraldehyde phosphate dehydrogenase (NADH)
glycerate phosphate kinase (ATP)
pyruvate kinase (ATP)
188
What is substrate-level phosphorylation?
- direct transfer of a high-energy phosphate to ADP or GDP
| - does not require electron acceptor or oxidative phosphorylation
189
What hormones is glycolysis influenced by?
insulin
glucagon
epinephrine
190
What is the influence of ATP on the regulation of glycolysis?
inhibitor of PFK1 and pyruvate kinase
191
What is the function of fructose-2,6-bisphosphate?
allosteric regulator that stimulates glycolysis and inhibits gluconeogenesis
192
What is the purpose of glycolysis?
1) removal of glucose from circulation
2) build up long-term stores of metabolic energy
Note: glycolysis isn't just for energy generation
193
In response to insulin, how does fructose-2,6-bisphosphate regulate PFK1 and fructose bisphosphatase?
1) insulin inhibits cAMP
2) PFK II remains active
3) PFK II converts F6P to F2,6BP
4) F2,6P stimulates PFK1 and inhibits fructose bisphosphatase
5) PFK 1 converts F6P to F1,6BP
194
In response to glucagon, how does fructose-2,6-bisphosphate regulate PFK1 and fructose bisphosphatase?
1) glucagon activates cAMP
2) cAMP activates PKA
3) PKA phosphorylates PFK II (becomes inactive)
4) F6P then goes on to gluconeogenesis
195
What stimulates PFK II?
fructose-6-phosphate
| AMP
196
In the presence of oxygen, what happens to NADH?
oxidized via ETS
197
In the absence of oxygen, what happens to NADH?
oxidized by fermentation (pyruvate>>lactic acid via lactate dehydrogenase)
198
Describe the Cori cycle.
lactate from the process of fermentation is transported to the liver where is will get oxidized back to pyruvate, which then can be used in glucoeogenesis
199
What is pyruvate kinase deficiency?
deprives RBCs of ATP, membrane potential is lost, result in hemolysis
200
What is hereditary fructose intolerance?
caused by deficiency in aldolase B. fructose-1-phosphate accumulates in the liver leads to damages and also depletion of phosphate pools, which affects glycogen breakdown
Symptoms: enlarged liver, hyperglycemia, and coma
Treatment: fructose-free diet (including sucrose)
201
What is galaactosemia?
- failure to utilize galactose in glycolysis
- results from defects in any of the following:
galactokinase
galactose-1-phosphate uridyl transferase
UDP-galactose epimerase
Treatment: galactose-free diet (including lactose)
202
What is the effect of arsenic on glycolysis?
- arsenic poisoning affects glycolysis by mimicking phosphate (at GAP dehydrogenase)
- inhibits ATP production>>no ATP gain from glycolysis
203
How do defects in glycolytic enzymes affect RBCs?
RBCs do not have mitochondria so its only source of ATP is through glycolysis. Any defects in glycolytic enzymes will lead to hemolytic anemia (inability to maintain membrane potential>>hemolysis)
204
How many ATP molecules are required for gluconeogenesis? What steps are they needed, including the enzymes involved?
4
1) pyruvate>>OAA (pyruvate carboxylase)
2) OAA>>PEP (PEPCK)
3) F1,6BP>>F6P (fructose-1,6-bisphosphatase)
4) G6P>> glucose (glucose-6-phosphatase)
205
What is the main regulatory step of gluconeogenesis?
F1,6BP>>F6P (fructose-1,6-bisphosphatase)
| *irreversible
206
What are the steps of gluconeogenesis that is irreversible?
pyruvate>>OAA (pyruvate carboxylase)
| F1,6BP>>F6P (fructose-1,6-bisphosphatase)
207
What are the major non-carbohydrate precursors for gluconeogenesis?
lactate (>>pyruvate)
amino acids (>>pyruvate or OAA)
glycerol (>>acetyl-CoA>>OAA)
208
What hormones is gluconeogenesis regulated by?
insulin and glucagon
209
What hormone is secreted in well-fed state? And what does it do?
insulin
inhibits gluconeogenesis
stimulates glycolysis
210
What hormone is secreted in starving state? And what does it do?
glucagon
stimulates gluconeogenesis
inhibits glycolysis
211
What are the three regulatory steps of gluconeogenesis?
1) formation of PEP
2) dephosphorylation of F1,6BP
3) dephosphorylation of G6P
212
What levels of NADH is optimal for gluconeogenesis?
low
213
Defect in the process of gluconeogenesis will lead to what conditions? Why?
1) hypoglycemia
- during fasting state, the body depends on gluconeogenesis to produce glucose.
2) metabolic acidosis
- glucose is primarily made from non-carbohydrates. dysfunction in making glucose lead to lactate buildup
214
What are the steps to synthesis of lactose?
1) UDP-glucose
2) epimerization to UDP galactose
3) lactose synthase condenses it with glucose to make lactose
215
What are the two functions of lactose synthase?
makes N-acetyllactosamine (glycosaminoglycan of ECM) and lactose
216
What is lactose synthesized from?
UDP-galactose and glucose
217
Where does gluconeogenesis occur?
liver (primarily), under extreme starvation the kidneys will as well
218
What is the purpose of pentose phosphate pathway?
produce NADPH and ribose
219
What is NADPH used for?
- anabolic reactions: synthesis of fatty acids, cholesterol, neurotransmitters and nucleotides
- also required for reduction of oxidized glutathion and p450 monooxygenases
220
What are the two phases of PPP?
oxidative and non-oxidative
221
What occurs in oxidative phase of PPP?
glucose is decarboxylated to form a pentose (ribose) and to reduce NADP (>>NADPH)
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What occurs in non-oxidative phase of PPP?
carbons in pentoses are rearranged to form glycolytic intermediates
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What is the regulated step of PPP?
glucose-6-phosphate dehydrogenase
