Metabolism Flashcards

1
Q

What does Catabolism/Anabolism do?

A

Catabolism - breaking down/exergonic/oxidation

Anabolism - building/endergonic/reduction

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2
Q

Define Catabolism/Anabolism:

A

Catabolism - generation of energy to drive vital reactions

Anabolism - synthesis of biological molecules

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3
Q

What are 3 properties of Catabolic pathways?

A
  1. Exergonic (release energy)
  2. Oxidative (e- transferred to NAD+ or NADP+_
  3. Energy captured as ATP
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4
Q

What are the 3 stages of Catabolism?

A
  1. hydrolysis of complex molecules to monomers
  2. conversion of building blocks to acetyl CoA in the mitochondria
  3. oxidation of acetyl CoA to carbon dioxide and water in ATP through Oxidative Phosphorylation (ETC)
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5
Q

Name 3 properties of anabolic pathways:

A
  1. Endergonic
  2. Reductive (hydride ion from NADPH used)
  3. ATP consumed
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6
Q

What type of reactions are carried out by dehydrogenase reactions?

A

oxidize a substrate by transfering Hydride ion to NAD+ and FAD

(dehydrogenase = think oxidation and NAD+ and FAD)

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7
Q

What are the major differences between Catabolism and Anabolism?

A

Catabolic products are similar, low molec. weight, and energy poor

Anabolic products are diverse, large, and energy rich

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8
Q

What is futile cycling?

A

Simultaneous synthesis and degradation

think Sisyphean

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9
Q

At least one of the steps in paired anabolic/catabolic pathways has a different…

A

enzyme

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10
Q

T/F

Paired pathways often occur right next to each other

A

False

they are often in different cellular compartments
i.e. - Fatty acid degradation occurs in Mitochondria
Fatty acid synthesis occurs in cytoplasm

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11
Q

Delta G Exergonic

Delta G Endergonic

A

less than 0

greater than 0

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12
Q

When delta G=0, then

A

equilibrium

forward rate=reverse rate

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13
Q

What 3 things do free energy changes predict?

A
  1. Direction of chemical reactions
  2. Equilibrium positions
  3. Amount of work that can be performed
    (the further from equilibrium the more work can be performed)
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14
Q

What can’t free energy changes tell us?

A

anything about the RATE of rxn

and is independent of the PATH of rxn

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15
Q

Can a rxn proceed if delta G(not) is positive

A

yes.

If delta G is negative

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16
Q

How can a thermodynamically unfavorable reaction be driven in the forward direction?

A

If coupled to highly exergonic rxn through a common intermediate.

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17
Q

What 3 things facilitate ATP hydrolysis?

A

Charge separation

Inorganic phosphate product stabilzed by resonance

direct product of hydrolysis ADP is ionized

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18
Q

Does ATP provide energy through hydrolysis?

A

NO

by group transfers

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19
Q

What are 2 ways to produce ATP?

A

Substrate level phosphorylation (minority)

Oxidative phosphorylation (mitochondria - ETC)

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20
Q

What are 3 levels of metabolic pathway regulation?

A

Allosteric (non-covalent bonding)

Hormonal

Concentration of enzyme (longest time frame)

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21
Q

What are two practical principles of bioenergetics (in terms of delta G and delta G0)?

A

A rxn can move forward even if delta G0 is positive (delta G has to be negative)

chemical rxns can be additive (coupling)

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22
Q

What are the 3 families of lipids?

A

Glycerophospholipids
Sphingolipids
Cholesterol

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23
Q

What is the prefix for a Glycerophospholipid?

A

Phasphatidyl… (or phosphatidic)

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24
Q

What are the 4 Sphingolipids?

A

Ceramide
Sphingomyelin
Glucosylcerebroside
Ganglioside

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25
What molecule is both a phospholipid and a sphingolipid?
sphingomyelin
26
What are the microdomains made up of cholesterol and sphingomyelin in the bilayer?
Lipid Rafts
27
What is a transmembrane protein called?
Integral
28
The membrane spanning part of an IMP (integral membrane protein) is usually ________(property) and ________ (structurally)?
Hydrophobic alpha - helices
29
An aquaporin is an example of
An IMP
30
What substances easily permeate membranes?
Gases and ethanol
31
What substances are slightly permeable to membranes?
Urea and water
32
Are ions permeable?
no
33
What are 6 ways to get something across a membrane?
Simple diffusion - gases and ethanol Facilitated diffusion - down electrochemical gradient Primary active transport (ATP) Secondary active transport (driven by ion moving down gradient carrying substrate) Ion channel Ionophore-mediated ion transport
34
Is ATP required for secondary active transport?
No. Not directly. | because it relies on a concentration gradient set up by Na/K pump which does rely on ATP
35
What type of transport goes against a concentration gradient?
Active Transport and Cotransport (with ions)
36
What are the 3 major types of membrane anchors? | Which are on the cytosolic side?
Acylation - fatty acyl to Gly Prenylation - NH3+ to Cys (both cytosolic) GPI anchor - PI, PE, and several sugars anchored through Asp (exterior cell)
37
How does glucose enter a cell?
Facilitated diffusion Membrane protein changes conformation (simple hand movement)
38
What are the 3 general classes of cell-surfaced receptors?
second-messenger catalytic intracellular
39
What are 4 approaches to cell signalling?
Endocrine Paracrine Autocrine plasma membrane-attached proteins (to adjacent cell)
40
What are 2 G protein coupled second messengers?
``` Adenylate Cyclase pathway (glucagon and epinepherine) Phosphoinositide pathway (growth hormone) ```
41
What is the function of the Nitric Oxide pathway?
Relaxation of smooth muscle
42
Give an example of a Sell-Surfaced Receptor and an Intracellular Receptor.
Insulin | Steroids
43
What is another name for 7TM receptors?
G protein coupled receptors (GPCR)
44
G-protein coupled receptor:
Hormone binds receptor in plasma membrane G-protein binds receptor GDP > GTP dissolution of complex, conformational change in G alpha G alpha to effector in plasma membrane GTP > GDP puts back together
45
Explain the Adenylate Cyclase cAMP pathway:
Epinephrine binds Beta-andrenergic receptor GDP > GTP activated Adenylate cyclase (protein/protein interaction) Adenylate cyclase causes ATP > cAMP, which activates Protein Kinase A
46
How do stimulatory and inhibitory (Gs and Gi) heterotrimers work in regards to cAMP
Gs activates cAMP Gi inhibits cAMP (through separate stimulatory/inhibitory receptors and G-complexes), affecting Adenylyl cyclase
47
T/F | cAMP inhibits Protein Kinase A
False cAMP activates the regulatory subunits of PKA to release its catalytic subunits it phosphorylates the targets Ser and Thr, and stimulates transcription activator CREB
48
Describe how Acetylcholine opens an ion channel (in neurotransmitter)
Acetylcholine binds, GDP > GTP in G-complex dissociates the complex G-beta binds adjacent channel, allowing K to flow out
49
How does the inactivation of a receptor work (two steps)?
1. Dissociation of signalling molecule | 2. phosphorylation of cell-side of receptor, followed by binding of Beta-Arrestin
50
How are GTP and cAMP inactivated?
GTP - hydrolyzed by intrinsic GTPase cAMP - by cAMP phosphodiesterase
51
What are two pathologies arising from a failure to inactivate signal?
Cholera and whooping cough (pertussis) both cases activate G-proteins, which increases cAMP, which leaves ion channels open
52
8 steps of phosphoinostide cascade | alternative 2nd messenger system for 7TM Receptors
1. GCPR/ligand dissociates G-beta inside cell, 2. PIP2 (phosphatidylinositol) > IP3 (inositol) 3. IP3 binds Ca+ ion channel 4. IP3- gated Ca2+ channel open 5-8. PKC (protein kinase C) activated by Ca, phosphorylates substrates
53
What does IP3 cause?
rapid release of Calcium from the endoplasmic reticulum | which further activates PKC and Calmodulin
54
Flow of Nitric Oxide pathway:
Ach > Ach GPCR > Phospholipase C > Ca/Calmodulin > NO synthase > NO receptor > PKG relaxation of muscle cell
55
What is the function of NO
Relaxes smooth muscle prevents platelet aggregation neurotransmitter in brain mediates tumoricidal/bactericidal actions of macrophage
56
What type of receptor is the insulin receptor?
Catalytic
57
What receptor has a protein kinase as part of its structure and is a good example of transduction?
Insulin
58
Describe 2 ways how a signal is relayed via intracellular receptors:
Hormone enters nucleus > binds receptor > transcription > translation > new protein >altered cell function Peptide or amine binds outside of cell and acts via 2nd messengers to alter gene expression
59
Name 5 Glycerophospholipids
``` Phosphatidic acid Phosphatidylethenolamine Phosphatidylcholine Phosphatidylserine Phosphatidylinositol ```
60
What is the free energy of a reaction?
Energy available to do work
61
NADH serves to carry...
electrons
62
[conc] 10 -2 M to 10 -4 M
Spontaneous
63
Which lipid is both a phospholipid and sphingolipid?
Sphingomyelin
64
Which variety of membrane transport coupling involves one species in and another out?
Antiporters
65
T/F | Signal transduction by catalytic receptors and intracellular receptors are both mediated by G-proteins
False
66
Which rxn pathways transform fuels into energy?
Catabolic
67
Exergonic rxns are:
spontaneous
68
Which enzyme begins the phosphoinositol cascade?
Phospholipase C
69
cAMP releases inhibition of, thereby activating...
PKA | Protein Kinase A
70
Glc enters most cells via
Facilitated diffusion
71
3 ways metabolism can be regulated:
Hormone Allosteric Compartmentalization
72
Ceramide is a...
Sphingolipid
73
What do both active transport and facilitated diffusion require?
Integral membrane protein
74
AA review. What 2 things does every Amino Acid have?
Amino group and Carboxyl group attached to alpha-C
75
pH=
-log [H+]
76
Why is pH biologically important?
charges in environment affect charge of molecule (and therefore shape)
77
Which acid is stronger, Formic acid pKa=3.75 Acetic acid pKa=4.76
Formic
78
Henderson-Hasselbach equation:
pH = pKa + log [A-]/[HA]
79
When is buffering optimal?
when acid = base
80
When acid = base,
pH = Pka
81
What is the term for an amino acid that can act either as an acid or a base?
Amphoteric | aka - zwitterion
82
What does an Amino Acid titration curve look like, and what is in the middle?
Two plateaus, each representing the pKa of the carboxyl and amino group. pI = average of the pKa's
83
Generally, the pKa's of carboxyl groups are around ______ , while the pKa's of Amino groups tend to be around ___.
carboxyl = around 2 amino = around 9
84
The pI, or isoelectric point, is defined as the _________. What will a molecule do in an electric field (like electrophoresis) at the isoelectric point?
point in which there is no net charge on a molecule won't move
85
In terms of charge, how is Histadine different than other AA's?
It has three dissociations (and therefore 3 pKa's)
86
Around how many polar and non-polar R groups are there for AA's?
10 polar | 10 non-polar
87
Which amino acid makes serotonin? | which makes dopamine?
Tryptophan | Tyrosine
88
What are the 5 amino acids that carry a charge?
Lysine, Arginine, and Histidine (positive) Aspartate and Glutamate (negative)
89
What is special about a peptide bond?
partial double bond character rigid and planar trans configuration uncharged but polar
90
What is the conventional direction of an Amino Acid?
From N (amino) to C (carboxyl)
91
Primary, secondary, and tertiary structure
AA sequence Beta sheets, alpha helix (can be parallel or antiparallel), Beta bends and turns. Folding (intra-structural interactions) - nonpolar usually inside, polar outside
92
What are structural motifs?
This is a supersecondary structure in which individual elements of secondary structure are combined into stable, geometrical arrangements (like helix bundles)
93
What stabilizes tertiary structure?
Non-covalent interactions (hydrophobic, ionic, and H-bonds) Covalent interactions (peptide bonds, disulfide bonds)
94
What is the difference between a polypeptide and a protein?
Polypeptide is one chain of AA's Protein can be made from multiple polypeptides. (this is Quaternary Structure)
95
What is the main driving force for the assembly Quaternary Structure?
Hydrophobic interactions
96
What is the difference between a fibrous and globular protein?
Fibrous - water insoluble, lack tertiary structure (think hair) Globular - water soluble (most proteins, etc)
97
If a molecule has a pKa, it is by definition a...
weak acid
98
At a pH below the pI, proteins carry a net ______ charge, and above the pI, proteins carry a net _____ charge.
positive | negative
99
What does a large pKa tell you about an acid?
It is very weak
100
What is in a conjugated protein?
a Prosthetic Group, such as lipids, metal (blood), phosphate groups, etc.
101
How do temperature and pH affect enzymes?
Temp - increase rate of rxn up to point pH - change charge, conformation, shape
102
What is the turnover number?
The maximum number of molecules of substrate an enzyme can convert to product (molecules converted/sec.)
103
How is catalytic efficiency determined?
Kcat/Km low Km means high efficiency/high affinity for substrate
104
T/F | Enzymes only bind one substrate
False. | Enzymes have a range of specificity
105
Give an example of an enzyme with high specificity. | Low specificity?
Urease - absolute specificity Chymotrypsin - breaks peptide bonds in a broad range (most specific for phenylalanine)
106
What is the additional ingredient many enzymes require to function?
A cofactor
107
Define Holoenzyme, Apoenzyme
Holoenzyme - Enzyme with its cofactor Apoenzyme - protein portion of the holoenzyme (no cofactor and inactive)
108
T/F | Coenzymes are non-protein organic molecules
True
109
What is the term for a tightly bound nonpolypeptide non-dissociating structure in an enzyme?
Prosthetic Group
110
Define: Vmax Km Kcat
max rate enzyme activity at substrate saturation substrate [conc] at 1/2 Vmax turnover number (substrate converted/time)
111
What term defines catalytic efficiency (how effective an enzyme is at catalyzing rxns)
Kcat/Km
112
What are 3 types of enzymatic reactions?
Random (creatine kinase) Sequential displacement (defined order) Double Displacement (enzyme > intermediate > enzyme)
113
What are the 5 key landmarks of a Michaelis-Menten graph
``` Vmax 1/2 Vmax Km 1st Order linear rxn zone 0 Order ```
114
The Km is referred to as the:
Michaelis constant
115
In a Lineweaver-Burke plot, what do the following indicate The x-intercept the y-intercept the slope
-1/Km 1/Vmax Km/Vmax
116
Describe the rxn when [S] is less than, equal to, and greater than Km
[S] less - optimal rxn velocity [S]=Km - half max velocity [S] greater - rxn approaches Vmax
117
What are the 3 types of enzyme inhibition? What are their effects on a lineweaver-burke plot
Competitive - goes for same active site (Vmax same, Km increases) Increase slope around the y-axis Noncompetitive - binds other site on Substrate, changes conformation Increase slope, but rotates at x-axis Uncompetitive - Vmax and Km decrease (traps enzyme) parallel slope
118
What are the effects of Allosteric positive and negative modifiers?
Allosteric positive - Increases affinity of enzyme for substrate Allosteric negative - Decreases affinity for enzymes to substrate
119
What is a proenzyme (aka zymogen), and what is an example?
Inactive enzyme precursor pancreatic and blood-clotting pathways (Trypsinogen)
120
What are isoenzymes?
Alternate forms of enzymes existing in different proportions in different tissues (tissue specificity)
121
``` Define: Aldose Ketose Enantiomer Epimer Glycosidic bond ```
aldose - carbohydrate with aldehyde as oxidized functional group ketose - carb with keto as oxidized functional group enantiomer - non-super imposable mirror images (hands) epimer - single carbon atom configuration difference glycosidic bond - carb/carb bond (hemiacetal to hydroxyl)
122
What is an oligosaccharide?
2-12 monosaccharides under - mono over - poly
123
What is a pyranose? | Furanose?
pyranose - hexagonal sugar furanose - pentagonal sugar
124
What is an anomer? | example?
special type of epimer alpha and beta-D-Glucose are anomers
125
Where is the hydroxyl group oriented in Alpha D glucopyranose? Beta D glucopyranose?
alpha - hydroxyl on bottom beta - hydroxyl on top
126
What can humans digest, alpha or beta glc?
Alpha = glycogen chains Beta = cellulose
127
How is glycogen branched?
Alpha 1,4 (linear) AND Alpha 1,6 (branched) linkages
128
What is starch made from?
Amylopectin (highly branched Alpha 1,4 and Alpha 1,6) and Amylose (spiral polymer of D glc)
129
What is cellulose made from
Linear chain of Beta 1,4 D Glucose
130
What makes up the disaccharides Maltose and Lactose? | Sucrose?
Maltose - 2 glc (Alpha 1,4) Lactose - 2 BETA D glc (Beta 1,4) glc/frc (Alpha 1, Beta 2)
131
What calcium dependent enzyme is found in saliva and what does it break down?
Salivary Amylase breaks down Alpha 1,4
132
What breaks Alpha 1,4 glycosidic bonds in the mouth? | What breaks them in the small intestine?
Salivary Amylase Pancreatic Amylase
133
What 4 brush border enzymes break down disaccharides?
Isomaltase, maltase, lactase, and sucrase
134
What does Isomaltase break down?
Alpha 1,6 glycosidic bonds
135
How does glc move from the lumen to the blood?
Symporter (secondary active transport) into enterocyte (cytosol) Glc then moves through basolateral membrane through GLUT2 transporters (integral membrane proteins) by Facilitated Diffusion
136
Describe the role of glc transporters in sugar metabolism.
GLUT2 IMP's move glc down concentration gradient through Facilitated Diffusion
137
What are 4 effects of fiber in the the diet?
Increase stool volume Increase stool softness Decrease transit time Increase satiety
138
What 2 things does passage of undigested carbohydrate into the large intestine cause?
Osmotic diarrhea Bacterial fermentation of carbohydrate to 2 and 3 C fragments (plus carbon dioxide and hydrogen gas)
139
What is the most common disaccharide enzyme deficiency? What disaccharide enzyme deficiency hasn't been observed?
Lactase Maltase
140
What oral bacteria attaches to the tooth surface and is a precursor to plaque? What occurs after attachment?
S. mutans biofilm wall builds and acidic bacterial waste leeches calcium out of enamel
141
What makes up the bacterial biofilm wall of S. mutans?
Dextran - made from Alpha 1,3 glycosidic linkage (no known enzyme)
142
``` What type of linkages are in the following: Glucose Starch Glycogen Cellulose Dextran ```
glc: Alpha 1,4 (mostly) and Alpha 1,6 (some) starch: Alpha 1,4 glycogen: Alpha 1,4 cellulose: Beta 1,4 Dextran: Alpha 1,3
143
What two disaccharide species are synthesized together?
Sucrase-Isomaltase | they are one unit
144
Where does glycolysis occur, and what are its aerobic and anaerobic products?
cytoplasm glucose > pyruvate (aerobic) glucose > pyruvate > lactate (anaerobic)
145
What does 1 molecule of glucose yield in glycolysis?
2 ATP (net) 2 pyruvate 2 NADH
146
What does the energy investment phase of glycolysis consist of?
Phosphorylation of glc > glc 6 phosphate (Step 1) - costs 1 ATP Frc-6-phosphate > Frc 1,6 bisphosphate (via PFK-1) - costs 1 ATP (this results in TWO Glyceraldehyde 3 phosphates)
147
Explain the energy payoff phase of glycolysis.
Glyceraldehyde-3-phosphate > 1,3 bisphosphoglycerate (this step requires the reduction of NAD to NADH) > 3 - Phosphoglycerate 1 ATP (two steps) > Phosphoenolpyruvate > Pyruvate 1 ATP
148
What type of phosphorylation occurs in Glycolysis?
Substrate-level phosphorylation
149
What is the chief role of glycolysis in skeletal muscle? | Liver?
supply ATP for muscle contraction excess glc in liver converted to fat
150
Why do erythrocytes only derive ATP through anaerobic glycolysis?
No mitochondria (or other organelles)
151
What happens to glc in the brain?
It is oxidized completely to carbon dioxide and water (process begins with glycolysis)
152
Where are GLUT 1-5 found? | glucose transporters
GLUT1 - brain and rbc GLUT2 - liver, kidney, intestine, beta cells GLUT3 - nearly all cells GLUT4 - muscle/adipose (insulin-dependent isoform) GLUT5 - small intestine
153
What are some insulin-insensitive (insulin independent) tissues?
rbc's, leukocytes, lens of eye, cornea, liver, brain
154
What is the name of the cotransport symporter of glucose from lumen?
SGLT1
155
What are 3 main regulators of Glycolysis?
Hexokinase Pyruvate Kinase PFK1
156
What enzyme is allosterically inhibited by Glucose-6-Phosphate?
Hexokinase (aka Glucokinase)
157
What are the 3 irreversible steps in glycolysis?
hexokinase phosphofructokinase I pyruvate kinase
158
What is the major committing step of glycolysis, and what is its enzyme?
Step 3 (frc-6-phosphate > frc-1,6-bisphosphate) PFK-1
159
What 2 things regulate hexokinase activity in muscle cells?
Inhibited by high [conc] glc in blood Inhibited by high [conc] glc-6-phosphate
160
What is hexokinase called in the liver? | Does it saturate?
Glucokinase | no
161
What activates PFK-1? What de-activates PFK-1?
activated by: frc-6-phosphate, ADP, AMP, frc-2,6 bisphosphate decreased by: ATP, citrate
162
What is the last irreversible step of glycolysis? | What enzyme catalyzes?
PEP (phosphoenolpyruvate) > pyruvate Pyruvate Kinase
163
What inhibits Pyruvate Kinase activity?
ATP covalent modification high [conc.] Acetyl CoA long chain fatty acids
164
Describe the differing kinetic characteristics of Hexokinase and Glucokinase.
Hexokinase has a low Km, which means a high affinity for glc Glucokinase has a high Km, which means a low affinity for glc in liver cells (why? cells need glc for fuel. excess goes to liver for storage)
165
What do all GLUT transporters have in common?
All are IMP's using facilitated diffusion and allow glc to travel down its concentration gradient.
166
GLUT 1-4 | Is their Km high or low, what does that mean?
GLUT1 - low Km, high affinity for glc GLUT2- highest Km, low affinity for glc GLUT3- low Km, high affinity for glc GLUT4- low Km, high affinity for glc
167
``` Describe the tissue specific roles glc plays in the following: Skeletal muscle Liver cells Erythrocytes Brain ```
Muscle - glc chief in supplying ATP for contraction Liver - excess glc stored RBC's - anaerobic glycolysis of glc only Brain - exclusively glc (using glycolysis, TCA, and oxidative phosphorylation)
168
What type of channels are found in the outer membrane of mitochondria, and what do they allow to pass through?
Porins | Allow Pyruvate through
169
What is found in the double layered inner membrane in the mitochondria and what is allowed to pass through?
Electron carriers I-IV, ATP synthase, Cristae Impermeable to pretty much everything, even gases and especially H+
170
What is contained in mitochondrial matrix?
Pyruvate dehydrogenase complex TCA enzymes Fatty acid Beta-oxidation enzymes AA oxidation enzymes
171
At the end of glycolysis, what are the 4 metabolic options for pyruvate?
Pyruvate can be converted to: Lactate (anaerobic) Alanine (AA) Acetyl CoA (then TCA) *pyruvate dehydrogenase complex Oxaloacetate (then TCA or Gluconeogenesis - anaplerotic)
172
Under what conditions does the metabolite (pyruvate) proceed to the Citric Acid Cycle?
When there isn't much Acetyl CoA | Acetyl CoA either upregulates or downregulates Pyruvate conversion into Acetyl CoA, depending on its concentration
173
What happens to pyruvate if the Acetyl CoA concentration is low?
Pyruvate > Acetyl CoA
174
What happens to pyruvate if the Acetyl CoA concentration is high?
Pyruvate > Oxaloacetate
175
How does pyruvate enter the mitochondrial matrix?
Antiports (secondary active transport) with -OH via a Porin catalyzed by Pyruvate Translocase
176
What happens to pyruvate upon entry into the mitochondria?
Attaches to PDHC | pyruvate dehydrogenase complex
177
What are the 5 co-enzymes for the PDHC, and what are they derived from (4/5)?
``` TPP Thiamine (B1) Pantothentate CoA-SH (B5) FAD Riboflavin (B2) NAD niacin (B3) Lipoic acid ```
178
Describe the conversion of Pyruvate into Acetyl CoA. What enzyme does this? Is it reversible?
PDHC (pyruvate dehydrogenase complex) is enzyme. decarboxylation (loss CO2) NAD > NADH S-CoA (power pack) Not reversible (very negative delta G)
179
Name 5 allosteric inhibitory molecules for PDHC.
``` ATP Acetyl CoA NADH GTP long chain fatty acids ```
180
Name 4 allosteric activating molecules for PDHC.
AMP CoA NAD+ Ca2+
181
Describe the two covalent regulatory mechanisms of PDHC.
Phosphorylation of PDHC (inhibition) Glucagon > GCPR > cAMP > PKA > phosphorylates Dephosphorylation of PDHC (activation) Insulin > Tyrosine Receptor Kinase > phosphatase > PDHC
182
Each turn of the Citric Acid Cycle feeds in ___ Carbons in the form of Oxaloacetate, and gives off ____ Carbons in the form of Carbon dioxide.
2 | 2
183
The 4 redox rxns in the citric acid cycle yield:
3 NADH | 1 FADH2
184
What is the 1 high energy phosphate bond formed with every turn of the citric acid cycle?
GTP
185
What are the 4 mechanisms of regulation in the citric acid cycle?
PDHC rxn Citrate Synthase rxn Isocitrate Dehydrogenase rxn (decarboxylation) Alpha - Ketoglutarate Dehydrogenase rxn (decarboxylation) (these are in order)
186
What inhibits the strongly exergonic steps in the CAC?
high ATP, NADH, and Citrate concentrations
187
Why is the CAC important for biosynthesis?
Citrate, alpha-ketoglutarate, succinyl CoA, and Oxaloacetate all create 4C and 5C intermediates that serve as precursors for a variety of products.
188
What pathways do the precursors Citrate and Oxaloacetate enter from the CAC?
Citrate - Fatty acids and steroids Oxaloacetate - Aspartate, AA's, purines, pyrimidines, GLC
189
How is Sorbitol created?
Glc > Mannose > Frc-6-P > Sorbitol
190
What cells create Sorbitol and why? | What are the effects of too much sorbitol?
Cells, like lens of eye and schwann - that allow easy import of glc but have no way of converting sorbitol to frc Osmotic effects and swelling
191
What happens if a cell doesn't want to give up its phosphates when glucose enters?
It converts glucose to Sorbitol
192
What does the PPP (pentose phosphate pathway) | (aka - Hexose monophosphate shunt and phosphogluconate pathway) produce?
NADPH | Ribose-5-Phosphate
193
What tissues have active PPP's?
Mammary, testes, ovary, adrenal cortex (steroid) Adipose Liver RBC's (any tissue synthesizing fatty acids and steroids)
194
What is the oxidative pathway of the PPP?
G-6-P > lactone > Ribulose-5-P | isomerization changes to ribose-5-P
195
What occurs in the PPP if cells need NADPH more than ribose-5-P?
The Non-Oxidative pathway Carbon atoms of ribose-5-P can be recycled/rearranged
196
What does reduced glutathione do?
detoxifies hydrogen peroxide to water
197
What is the enzyme that rids the cell of hydrogen peroxide?
Glutathione peroxidase
198
How does the cell regenerate glutathione?
Reduces it with NADPH (from the PPP)
199
T/F | Gluconeogenesis is a universal pathway.
True
200
What is the major function of gluconeogenesis? | 3 Additional functions?
Major: provides glc to brain, nervous system, etc when blood sugar low Minor: Control acid/base balance Maintain AA balance Provide biosynthetic precursors
201
Name 4 important precursor molecules to glucose.
lactate pyruvate glycerol most AA's
202
What is the major site of GNG in the body?
Liver | but also kidney
203
T/F | GNG is the reverse of glycolysis
False | there are 3 irreversible steps of glycolysis GNG needs to get around
204
Where do lactate and some AA's enter the GNG pathway?
Step 1 | pyruvate > oxaloacetate
205
Where two places do AA's enter the GNG pathway
Step 1 (pyruvate > oxaloacetate) Step 2 (oxaloacetate > phosphoenolpyruvate)
206
Where does glycerol enter the GNG pathway?
Step 7 | Glyceraldehyde-3-P > dihydroxyacetone phosphate
207
In the beginning of GNG, what enzyme initiates the molecule's exit from the mitochondria? (this is a key enzyme - bypass 1)
Pyruvate carboxylase
208
What are the steps the pyruvate molecule takes to exit the mitochondria in GNG?
Pyruvate (pyruvate carboxylase) > oxaloacetate > Maltase > oxaloacetate (maltase can cross the IM)
209
What enzyme simultaneously decarboxylates and phosphorylates oxaloacetate in GNG?
PEP carboxykinase
210
What does anaplerotic mean?
replenishing
211
What is lactate converted to in the liver?
Pyruvate then goes to mitochondria and enters GNG path
212
In GNG, what catalyzes Frc 1,6 bisP > Frc-6-P? | bypass 2
Fructose 1,6 bisphosphatase
213
What is the enzyme that coverts Glc-6-P to D-Glc? | this is bypass 3 and allows molecule to exit cell
Glucose 6-Phosphatase
214
From whence comes glycerol in the GNG pathway? what is it broken down into?
triacylglycerol (fat) glycerol > glycerol 3-P (by glycerol kinase)
215
How many high energy bonds are required to synthesize glucose from pyruvate? How many generated from breakdown from glucose to pyruvate?
4 ATP + 2 GTP = 6 bonds (also 2 NADH required) 2 ATP
216
What stimulates pyruvate carboxylase (and thus pyruvate dehydrogenase (and thus GNG)? this is control point 1!
Acetyl CoA
217
What moves the GNG/Glycolytic pathway (control point 2!) between frc-1,6-bisphosphate and frc-6-P?
low energy (high levels AMP/ frc-2,6-BP depressed citrate/ATP/H+) moves toward Frc-1,6BP (glycolytic) high energy (low frc-2,6-BP/AMP and high Citrate) moves toward Frc 6-P (GNG)
218
How does fructose 2,6-BP play a role in whether glc will be degraded or synthesized?
Starvation > glucagon > frc 2,6-BP drops | this encourages GNG by decreasing activity of PFK1 and increases activity of phosphatase
219
T/F | Glucagon decreases the activity of pyruvate kinase.
True
220
What is the Cori Cycle?
(muscle) glc > lactate (liver) lactate > glc and back to muscle
221
What is glc 2,6-BP regulated by?
Insulin/Glucagon ratios
222
What does liver do with glc and what does muscle do with glc?
Liver: converts glycogen > G-6-P > Glc > blood (maintains blood glc levels) Muscle: glycogen > G-6-P > Glc > ENERGY
223
T/F | Glycogen is in almost every cell of the body
True
224
Describe the structure of glycogen.
Glc connected by Alpha 1,4 bonds and branches of Alpha 1,6 bonds Reducing ends inside, non-reducing (C1) outside
225
Where is most glycogen stored in the body?
Skeletal muscle | but liver stores 4-7x more/weight
226
What is the key enzyme in glycogen synthesis?
Glycogen synthase
227
Glycogen synthesis pathway: | key enzyme:
Glc > G-6-P > G-1-P > UDP > Glycogen Glycogen synthase
228
What makes the Alpha 1,6 linkages in glycogen?
Glycosyl 4,6 transferase
229
Glycogen breakdown pathway plus 3 options:
glycogen > G-1-P > G-6-P then, 1. glycolysis > pyruvate 2. glucose (via glc-6-phosphatase) 3. PPP
230
What is the key enzyme in the breakdown of glycogen?
Glycogen Phosphorylase
231
What primer does Glycogen Synthase need to carry out glycogen synthesis? What bond does it catalyze?
Glycogenin Alpha 1,4 glycosidic
232
What helps glycogen synthase by acting as a sort of scaffolding on which to build glycogen?
sugar nucleotides
233
What enzyme do glycogenesis and glycogenolysis have in common?
phosphoglucomutase
234
What are the 2 forms of Glycogen Synthase, and how are they regulated hormonally?
A (active): insulin + OH = not phosphorylated (make glycogen) B (inactive): Phosphate + glucagon
235
What are the 2 forms of Glycogen Phosphorylase, and how are they regulated hormonally?
A (active): Phosphate + glucagon (make glucose) B (inactive): Insulin + OH
236
Describe the allosteric regulation of glucose.
Increasing glc concentration stores glycogen Increasing AMP concentration liberates glycogen
237
Why is Von Gierke's disease so detrimental to the liver but not to muscle cells?
defect in G-6-Phosphatase won't allow glc to leave liver. muscle uses it all
238
What are some symptoms of Von Gierke's?
hypoglycemia hyperlipidemia lactate acidosis enlargement of liver
239
Why can we make fat from carb but not carb from fat?
Pyruvate > Acetyl CoA via pyruvate dehydrogenase is irreversible
240
T/F | the Citric Acid Cycle is regulated by availability of NAD+
True
241
Ratio of NAD+/NADH | Ratio of NADP+/NADPH
1000/1 (lots NAD+) | 0.1 (lots NADPH)
242
What is the purpose of NADPH?
defeats free radicals and biosynthesis
243
What is a rate limiting step (PPP) with lots of clinical implications (think RBC's)
G-6-P Dehydrogenase favaism
244
How much ATP is made from each NADH and FADH2 molecule in the ETC?
NADH - 2.5 FADH2 - 1.5 (each donate 2 electrons)
245
What enzymes are involved in NADH/FADH2 reduction/oxidation
oxidoreductase/dehydrogenase
246
From what vitamin is NAD synthesized?
Niacin
247
FADH2 is considered to be...
a redox cofactor
248
What 3 places is NADH is formed in catabolism?
glycolysis pyruvate dehydrogenase complex CAC
249
What structure in the outer membrane of mitochondria make it permeable to most ions and small molecules?
Porins
250
T/F | The inner mitochondrial membrane is impermeable to most ions and small molecules.
True
251
What two molecules have transporters to cross the IMM?
G-3-P and Malate
252
What molecules are paired to make the malate shuttle run?
Oxaloacetate > Malate (NADH > NAD+) > (NAD+ > NADH) Oxaloacetate > Alpha-ketoglutarate (comes back out) Glutamate > Aspartate (comes out)
253
Where is the low pH found in the mitochondria?
Intermembrane Space
254
The IMM is folded into: | and is only permeable to:
Cristae | CO2, O2, H2O
255
What is the destination of NADH and FADH2 (both products of the CAC) in the ETC?
NADH - Complex I | FADH2 - Complex II
256
What are the two prosthetic groups in Complex I of the ETC? | How many H- are moved to the IMM with each NADH?
FMN > Fe-S 4 H-
257
What prosthetic group is found in Complex I, II, and III?
Fe-S
258
What complex doesn't move hydrogen into the IMM?
Complex II | FADH2 complex
259
How do electrons in Complex I travel straight to Complex III?
CoQ
260
Complex I: | Effector molecule, enzyme, prosthetic groups, number Hydrogens transported to IMM
NADH NADH-Q oxidoreductase FMN (Flavin Mononucleotide), Fe-S 4
261
Complex II: | Effector molecule, enzyme, prosthetic groups, number Hydrogens transported to IMM
FADH2 Succinate Q dehydrogenase/reductase FAD, Fe-S 0
262
``` Complex III: receives electrons via transports electrons via prosthetic group Hydrogens transported to IMM ```
CoQ Cytochrome C Fe-S, Heme groups 4 (the Q cycle)
263
What is oxidized to Q in complex III?
Ubiquinol (QH2)
264
What is the last enzyme in the ETC?
Cytochrome C oxidase complex
265
Complex IV: | effector molecule, enzyme, prosthetic groups, number hydrogens transported to IMM
CoQ Cytochrome C oxidase Heme a & a3, CuA & CuB 2 (only one doesn't use Fe-S clusters)
266
Explain the Q cycle that occurs in Complex III:
Q pool > QH2 > Q from QH2, e- either 1. Cyt C1 and Cyt C 2. Q radical > QH2 > Q pool
267
What is the final receptor in Complex IV?
Oxygen
268
How are electrons passed to oxygen in complex IV?
2 cytochrome C pass electrons through CuA/CuB, HemeA/HemeA3/CuB HemeA3 to CuB (iron copper) peroxide bridge 2 more cytochrome C, and more electrons to the system cleaves off the oxygens when 2 Hydrogens cleave the peroxide bridge. 2 more hydrogens added releases 2 water molecules
269
What is a reduction potential?
Tendency of species to acquire electrons | the more positive, the greater the affinity
270
What electron receptor has the largest and most positive reduction potential?
Oxygen
271
What enzyme universally converts free radicals to hydrogen peroxide?
Superoxide dismutase | commonly found as tetramer with Mn in reactive center
272
What hypothesis involves ATP being synthesized via electrochemical gradient?
Chemiosmotic hypothesis
273
Can ATP synthase run in reverse?
yes
274
What two molecules have transporters to move across the IMM?
G-3-P (glycerol-3-phosphate) Malate
275
What enzyme is used in the Glycerol-3-Phophate shuttle and what is exchanged?
Glycerol-3-Phosphate dehydrogenase exchanges FADH2 for NADH
276
What is the defining feature of connective tissue?
Extra cellular matrix
277
What are the four main classes of molecules found in the ECM?
Fibers Glycoproteins Glycosaminoglycans Proteoglycans
278
What is the ground substance?
ECM without the fibers | composed of glycoproteins, glycosaminoglycans, proteoglycans
279
What is calcified ECM called?
teeth
280
What are the two main classes of macromolecules making up the ECM?
Proteoglycans (GAG's) Fibrous/Multi-adhesive proteins (collagen/fibronectin)
281
What are the 4 major classes of GAG disaccharides?
Hyaluronan Chondroitin sulfate Heparan sulfate Keratan sulfate
282
What class of GAG does not form proteoglycans?
Hyaluronan
283
What is the most abundant GAG in the body?
Chondroitin sulfate
284
What molecule is a long unbranched chain of polymers of repeated disaccharides containing an amino sugar?
Glycosoaminoglycans
285
What makes GAG's gels?
sulfate and carboxyl groups - for volume high density of negative charge (attracts water)
286
What is the overall function of GAG's?
maintains homeostatic environment
287
What is Heparin?
strong anticoagulant | not to be confused with Heparan - part of GAG structure
288
What is a proteoglycan?
A chain of GAG's (joined covalently to a membrane or protein structure) mostly carbohydrate by mass
289
What is the major structural proteoglycan found in cartilage?
Aggrecan
290
What molecule can be bound to but does not form Proteoglycans?
Hyaluronic acid
291
What strengthens the ECM and what gives it resilience?
Collagen | Elastin
292
What are 3 classes of Proteoglycans? | What are some of their structural motifs?
Small leucine-rich (SLRP's) - biglycan, decorin Modular - perlecan, agrin, aggrecan Cell-surface - syndecan
293
Describe a proteoglycan aggregate.
GAG's attached to long fibers forming Proteoglycans attached to Hyaluronate backbone (feathers on Hyaluronate)
294
Are Proteoglycan aggregates linked to a protein core?
NO Hyaluronate is apparently not protein
295
What molecule is considered the biological shock absorber?
Hyaluronate
296
How is Hyaluronan unique among the GAG's?
No sulfate
297
How are proteoglycans anchored to membranes?
Syndecan-1 (part of PG) binds to Chemokines (on cell)
298
Describe Proteoglycan synthesis.
tetrasaccharide linker connects GAG to Ser residue (O-linked) in the core protein. Then sugar nucleotides add sequentially by glycosy transferases Epimerizations/sufations occur prior to exocytosis
299
What is the result of abnormal proteoglycan catabolism?
arthritis, tumor invasions
300
What makes proteoglycans suseptible to proteases?
linear conformation | but they have a range of inhibitors
301
What ingredients are required to lysosomally catabolize proteoglycans?
3 Exolglycosidases 4 Sulfatases 1 Acetyl trasferase and step-wise removal of monosaccharides
302
What pathology is defined by enzyme deficiency, autosomally recessive or x-linked, severe and mild forms, and not apparent at birth?
Mucopolysaccharide (GAG) defects | aka Lysosomal storage disease
303
What molecules do not accumulate in Lysosomal storage disease?
Chondroitin sulfate | Hyaluronate
304
What molecule has both a GAG form and a proteoglycan form?
Hyaluronate
305
What two components of the ECM provide strength, shape and elasticity?
Collagen and Elastin
306
What two components of the ECM are multi-adhesive, providing attachment for matrix components as well as cells?
Fibronectin and Laminin
307
What integral membrane proteins connect ECM to cells?
Integrins
308
What is the most abundant protein in the body?
Collagen
309
What purposes do the major proteins found in the ECM serve?
Structure and Adhesion
310
Structure in the ECM is provided by...
Collagen and Elastin
311
Adhesion in the ECM is provided by...
Fibronectin and Laminin
312
Collagen is a glycosylated protein rich in what 4 AA's?
Glycine Proline Hydroxyproline and Hydroxylysine
313
The normal AA sequence of collagen is:
Gly-Pro-Y Gly-X-Hyp (Hydroxyproline) X,Y = any AA
314
How many types of collagen are there? | How many "major" types?
28 | 4
315
Where are the 4 major types of collagen found?
I Skin, bone, tendon, bv's, cornea II Cartilage, intervertebral discs III Blood vessels, fetal skin IV Basement membrane
316
What type of collagen accounts for 90% found in body?
Type I
317
What 5 steps of collagen synthesis occur in the ER and Golgi complex?
1. Synthesis of pro-alpha chain 2. Hydroxylation (pro and lys) 3. Glycosylation (selected hydroxylysines) 4. Pro-alpha chains self assemble 5. Procollagen triple helix forms
318
What are the 4 steps of collagen synthesis that occur outside the cell?
6. Secretion 7. Cleavage of propeptides 8. Self-assembly into fibril 9. Aggregation of fibrils into fiber
319
What type I collagen post translational modification stabilizes the triple helix?
Disulfide bond formation
320
What occurs in the propeptide cleavage step of collagen synthesis?
Cleavage of N- and C- terminals
321
What AA's form the cross linking residues that create the fiber in collagen synthesis?
Lysine
322
What does the hydroxylation rxn of proline and lysine residues require?
Vitamin C | scurvy
323
What is the extracellular copper enzyme that catalyzes formation of aldehydes from lysine residues in collagen synthesis?
Lysyl Oxidase
324
How does aldehyde formation from lysyl oxidase form collagen?
Aldehydes are highly reactive and spontaneously form bonds with other aldehydes (results in cross-linking)
325
How do non-fibrillar collagens differ in their primary structure?
No regular Glycine for tight helix
326
Are non-fibrillar collagens cleaved after secretion?
NO | so retain propeptides
327
Type IV collagen has lateral interactions between...
helical segments
328
Type IV collagen has what type of interactions between the globular domains?
head to head | tail to tail
329
Type IV is a ______ forming collagen found in ______.
sheet | basal lamina
330
What are the 3 steps of collagen degradation?
1. Enzyme binding 2. Unwinding triple helix 3. Cleavage of collagen peptides
331
What 2 enzymes have collagenase property?
Matrix metalloproteinases (MMP's) Cathepsins (L and K)
332
What does initial cleavage of collagen yield? | How is it cleared?
gelatin denaturation and protease digestion and phagocytosis
333
Which collagen pathology is characterized by long bone fractures prior to puberty? Which has perinatal lethality?
Osteogenesis imperfecta 1 (decreased type I synth) Osteogenesis imperfecta 2
334
What collagen pathologies result in translucent skin, hyperextensive skin, and joint hypermobility?
Ehlers-Danlos IV, VI, VII
335
What ECM fiber has a half life of 74 years?
Elastin
336
How is elastin assembled?
tropoelastin (soluble form) associates with fibrillin to assemble elastic fibers
337
What are tropoelastin cross-linkages formed between?
Lysines (catalyzed by LOX)
338
Where is elastin commonly found?
lungs, large bv's, elastic ligaments
339
What AA's are commonly found in elastin?
nonpolar - glycine, alanine, valine Proline (hydroxyproline) and lysine (no hydroxy form)
340
What protease inhibitor prevents emphysema, COPD, and liver cirrhosis by preventing elastin breakdown?
Alpha1-antitrypsin
341
What is the function of fibronectin?
binds cells to the ECM
342
What does fibronectin bind?
Integrin, collagen, fibrin, and heparan sulfate proteoglycans (syndecans)
343
T/F | Fibronectin is important for wound healing?
True fibronectin connects cytoskeleton to matrix
344
What is the name of the Type IV collagen pathology?
Allports syndrome
345
What are the 4 ECM proteins found in all basal laminae?
Laminin Perlecan Type IV collagen Entactin/Nidogen (glycoprotein)
346
What is a cross-shaped protein that is a major part of the basal lamina?
Laminin
347
What do the short and long arms of laminin bind to?
short - other laminin molecules long - bind to cells
348
What serve as receptors for fibronectin, collagen, laminin, fibrinogen, vitronectin, and lg superfamily?
Integrin