Biochemistry II Flashcards
(158 cards)
1
Q
What is biotransformation?
A
Metabolic process to facilitate the excretion of endogenous and exogenous substances (mainly occurs in the liver) by altering their chemical structure
2
Q
What types of substances are excreted by biotransformation (2)?
A
endogenous and exogenous substances
3
Q
How many phases are possible in the biotransformation?
A
Phase 1, 2 and 3
4
Q
What can happen to the substances by catalytic enzymes (3)?
A
substance inactive, active or toxic
5
Q
Where does a majority of biotransformation occur? What are some other sources of this processes (6)?
A
Majority of biotransformation occurs in the hepatocytes but also extrahepatic sources such as adipose, intestine, kidney, lung, placenta, and skin
6
Q
What effects biotransformation (6)?
A
Affected by age, gender, nutritional status, disease state, meds and genetics
7
Q
What does phase 1 yield?
A
Yield a polar, H2O soluble metabolite that is still active
8
Q
What happens to many of the substrates after phase 1?
A
Many become the substrates for Phase 2 reactions
9
Q
What are redox reactions?
A
Oxidation-Reduction
Redox reactions require that electrons be transferred or removed to either reduce or oxidize a particular substrate or molecule
10
Q
What happens to electrons during oxidation?
A
electron loss (May manifest in an increased in ionic charge)
11
Q
What happens to electrons during reduction?
A
is election gain
12
Q
When an atom is _________ in a reaction, it loses electrons to another atom.
A
oxidized
the oxidized atom/compound is a reducing agent/reductant
13
Q
Atoms that gain electrons are _________.
A
Reduced, it is an oxidizing agent/oxidant
14
Q
Fe + 2 HCL yields FeCl2 + H2
What is being oxidized or is the reducing agent?
A
Fe
15
Q
Fe + 2 HCL yields FeCl2 + H2
What is being reduced or is the oxidizing agent?
A
HCl
16
Q
What is oxidation?
A
usually manifests as increasing bonds to oxygen or decreasing bonds to hydrogen (electron transfer versus dehydrogenation
17
Q
What type of reactions do oxidation produce?
A
Exothermic reaction
18
Q
What are the different examples of oxidation in the body?
A
- Cytochrome P450 monooxygenase system (P450, CYP 450)
- Flavin-containing monooxygenase system
- Monoamine oxidase (MOA)
- Alcohol and aldehyde dehydrogenase
- Peroxidases
19
Q
What is reduction?
A
Opposite of oxidation
20
Q
What is the major oxidating system in the body?
A
Cytochrome P450 monooxygenase system (P450, CYP 450)
- diverse system with ~57 isoforms)
- Prone to many interactions (can be induced or inhibited)
21
Q
What is involved in the reduction process?
A
P 450 microsomal system involved
22
Q
What state does reduction usually occur?
A
More prone to occur in anaerobic states
23
Q
When is reduction usually seen?
A
Seen with decreased bonding with oxygen or increased bonding with hydrogen
24
Q
What are two substrates present in all organisms? Why are they are important?
A
Nicotinamide adenine dinucleotide (NAD+/NADH) along with its phosphorylated form (NADP+/NADPH) are two molecules present in all organisms. Factors in catabolic and anabolic processes.
25
What is hydride H+?
coenzyme as a carrier: the anion of H
26
What are the NADH/NAPH?
reduced forms
27
What is happening in the following molecule?
Drug + O2 + H+ + NADPH ➡️ Drug-OH + H2O + NADP+
```
NADPH used (not ATP)
Splitting of oxygen molecule
```
28
Where does hydrolysis occur? What does it not involve?
Usually occur outside the liver (does not involve P450 enzyme system)
29
What doe esters enzymes usually react with?
ester bond of compounds (and amides)
30
What is used in the process of hydrolysis?
H2O is used in the process (can be substitution, elimination, solvation reactions)
-These agents tend to be shorter acting than their counterparts
31
What process is important in the digestion of saccharides, proteins and fat?
Hydrolysis
32
What is the opposite reaction of hydrolysis?
condensation (some esters are formed by condensation of alcohol and carboxylic acid- would be subject to hydrolysis)
33
What is an example of condensation?
ester local anesthetics
34
Where are hydrolytic enzymes most commonly found (4)?
plasma, RBCs, GI, synaptic clefts
35
What are some other examples of hydrolytic enzymes?
Proteases, lipase, Phosphatase & Esterases
36
What are drug examples in hydrolysis (6)?
esmolol, ester local anesthetics, remifentanil, acetylcholine, succinylcholine, ASA
37
What does phase 2 yield (2)?
- large polar metabolite by adding a hydrophilic group to form a H2O soluble, inactive compound that can be readily excreted
- Synthetic reactions
38
What is an important component of conjugation?
Most common form of congugation: Conjugation with glucuronic acid involves the P450 (synthesized from glucose and added to a lipid-soluble drug to render H2O soluble)
39
What is the hallmark of phase 2?
Conjugation
40
What are glucuronide conjugates excreted in?
bile/urine (example: bilirubin, steroid/thyroid hormones)
41
What is flood's opinion of conjugation?
Flood considers a Phase 1 reaction since a 1-step process as becomes hydrophilic and does not need further biotransformation (ONLY conjugation that uses microsomal enzymes) (Nagelhout: Phase 2)
42
What is the goal of conjugation?
render a lipid soluble agent polar/H2O soluble for elimination (drug may undergo Phase 1 then further transformation via Phase 2)
43
What are the types of enzymes in the conjugation?
Numerous enzymes: -transferases
44
What are some examples of agents that only goes through Phase 2 (3)?
if agent already has a functional group): Propofol, morphine, midazolam`
45
What can conjugation and p450 have on some agents?
render some agents into active metabolites with their own metabolic profile
46
What does phase 1 refer to?
Phase 1 refers to redox and hydrolysis reactions to render a substance more polar for excretion of placing carboxy or hydroxy groups to prepare for phase 2 (adding a functional structure)
47
Where does the P450 enzyme system occur?
endoplasmic reticulum of hepatocytes and mitochondria
48
What is the site of action of hydrolysis?
sites of action via hepatic/extrahepatic cellular enzymes, plasma; type of enzymes vary
49
What does phase 2 refer to?
Phase 2 involves coupling a compound or its metabolite to another compound
50
What are examples of phase 2 (5)?
glucuronidation, methylation, acetylation, sulfation, or conjugation with glutathione or certain amino acids (glycine, taurine, glutamic acid
51
Where does phase 2 occur (4)?
Occurs in the cytosol, membranes, mitochondria, ER
52
What is a synthetic reactions?
new compound created
53
When does phase 3 occur?
post-phase 2 (chemical substance undergoes further metabolism and excretion
54
What occurs during phase 3?
Xenobiotic transporters in the liver (think bile excretion), kidneys, and small intestines remove xenobiotics (toxins, antigens) and metabolites from cells
55
What type of process is phase 3?
Antiporter/Efflux porter systems (active process)
56
What are some examples of phase 3 (3)?
ATP-binding cassette (ABC), Solute carrier (SLC) transporters and P-glycoprotein
57
What is important the components of the mitochondria layer?
There is an inner layer and outer layer of the mitochondria
58
What are carbs broken down into?
simplest forms (glucose, galactose, fructose)
59
What is galactose and fructose are converted to? What changes glucose enter into the cell?
Glucose-6-phosphate in the liver (glucokinase changes glucose entering any cell into the same)
Glucokinase
60
What does galactokinase convert?
Galactose phosphorylated (think energy) to galactose-1-phosphate
61
What is the ultimate produce of glucose breakdown? Which enzyme is involved?
further enzymatic processes is glucose-6-phosphate or glycogen by way of glucose-1- phosphate
62
What is Glucose-6-PHOSPHATE? What liberates it?
glucose within the cell- “trapped.” Must be liberated by glucose phosphatase to enter bloodstream in its free form (liver to bloodstream to other cells)
63
What is fructose phosphorylated?
has own catabolic pathway
64
What step does fructose phosphorylated enter into the kerb cycle?
enters glycolysis as a glyceraldehyde late in the sequence right before pyruvate is generated (or makes glycogen)
65
What is the process of fructose phosphorylated?
fructose-1-phosphate by fructokinase
66
What does insulin facilitate?
rapid entry of free-form glucose into the cells
67
What are other ways glucose enters the cell (3)?
enters by facilitated/passive diffusion (concentration gradient via GLUT), active Na+/glucose co-transport (SGLT), active transport via ATP
68
What are the four step process for cellular respiration (glucose to energy)?
-Glycolysis
-Pyruvate dehydrogenase (pyruvate oxidation)
-Kreb’s Cycle
-Oxidative phosphorylation (electron transport)
via NAD/NADH+ and FAD/FADH2
69
What is NADH? How many ATP does it yield?
nicotinamide adenine dinucleotide (NADH), a coenzyme derived from vitamin B3 or niacin (net 3 ATP)
70
What is FADH2? How many ATP does it yield?
flavin adenine dinucleotide (FADH2), a coenzyme derived from Vitamin B2 or riboflavin (net 2 ATP)
71
What are the forms that NADH/FADH exist?
-can exist in the reduced form or oxidized form: NADH/FADH2 – reduced form (“loaded”) and NAD+ & FAD+
72
What is the importance of NAD+ & FAD+?
Both participate in oxidation and reduction reactions and help in the transfer of electrons from one substrate to the other.
73
Can be synthesized in the body?
Yes
74
What do NAD+ & FAD+ take part in?
Both molecules take part in metabolic pathways which include carbohydrate, fatty acid, amino acid and nucleotide metabolism
75
What is the pre Kreb cycle?
Glycolysis
76
What happens to glucose during glycolysis?
A 6-carbon sugar—undergoes a series of chemical transformations.
77
What is the end byproduct from glycolysis?
2 individual pyruvate molecules, a 3-carbon organic molecule
78
How many ATP is made during glycolysis?
2 ATP
79
How many nadh is made during glycolysis?
2 NADH
80
What is produced from glycolysis?
ATP is made and NAD+ is converted (REDUCED) to NADH
81
What forms glycogen?
Glucose-6-phosphate converted to Glucose-1-phosphate to form glycogen or enters metabolic pathway
82
What is the limiting process of glycolysis?
Phosphofructokinase (PFK)
Enzyme for fructose-6-phosphate to fructose-1,6 bisphophate
83
What is Phosphofructokinase (PFK)?
The reaction by PFK is thermodynamically favorable and practically irreversible
84
What is fermentation?
is the process of glycolysis in anaerobic conditions- limits the oxygenation available to oxidize NAD. Pyruvate becomes the driver
85
What is a negative byproduct of glycolysis in anerobic conditions?
Lactate acid (it is transported to liver and converted to glucose)
86
What is the total ATP created during Glycolysis? How many is actually yielded?
4 ATP; 2 ATP
87
What is another pre Kreb's cycle?
Pyruvate Oxidation
88
What happens to pyruvate oxidation?
EACH pyruvate from glycolysis goes into the mitochondrial matrix—the innermost compartment of mitochondria.
89
What happens to pyruvate once it enters the mitochondrial? What is it it bounded too?
There, pyruvate is oxidized via NAD+ to a 2- carbon molecule (an acetyl group) that is bound to Coenzyme A
90
What is generated from pyruvate oxidation?
One pyruvate= 1 CO2 (is generated as the carboxyl group is released) and 1 NADH
Total from one glucose is 2 CO2 and 2 NADH
91
What is the byproduct of pyruvate oxidation?
Acetyl-CoA
92
What does Acetyl-CoA interact with during the kreb's cycle? What does it form?
reacts with oxaloacetate forming citrate to enter a series of enzymatic
93
What is yielded from the Kreb's cycle?
From one pyruvate= 2-CO2- 3 NADH, 1 FADH, and 1 ATP
From 2 pyruvate or one glucose molecule= 4-CO2- 6 NADH, 2 FADH, and 2 ATP
94
What is the end product of the kreb cycle?
Oxaloacetate
95
Each pyruvate molecule goes through a _______ process (original glucose molecule generates 2 pyruvates)
Kreb cycle process
96
What happens when you break down a carbon?
One less carbon and CO2 is formed
97
What is important about CoEnzyme A (COA)?
Role in the synthesis and oxidation of fatty acids and oxidation of pyruvate in the citric acid cycle (versatile metabolic enzyme)
98
What is CoEnzyme A (COA) synthesized from?
Naturally synthesized from pantothenate (vitamin B5)
99
What forms Acetyl CoA?
Pyruvate is oxidized to and combined with CoEnzyme A (Pyruvic acid is an alpha keto acid- carboxylic acid compound)
100
Why is CoEnzyme A (COA) important for in the Kreb's cycle?
In its acetyl form: Provides an acetyl group for reaction in the Kreb’s cycle
- Acetyl group : methyl group single-bonded to carbonyl
- There is an acryl-CoEnzyme
101
What is an acetyl group?
methyl group single-bonded to carbonyl
102
What are the end results NADH, FADH2, GTP or ATP, CO2 from 1 pyruvate?
3-NADH, 1 FADH2, 1 GTP OR ATP, 2 CO2
103
What are the end results NADH, FADH2, GTP or ATP, CO2 from 2 pyruvate or 1 glucose?
6-NADH, 2 FADH2, 2 GTP OR ATP, 4 CO2
104
What is oxidative phosphorylation?
Oxidation of high-energy electron carriers NADH and FADH2 are passed along a chain of membrane-based enzymatic reactions (Electron-Transport Chain)
105
What stage do you get most ATP development?
Electron Transport Chain
106
What happens to energy released from oxidative phosphorylation?
Used to pump protons out of the mitochondria inner (the electrons that are conveyed by NADH/FADH2 do the work to move the protons)
107
Where does the electron transport chain occur?
mitochondria inner
108
What happens to hydride during the electron transport chain?
must lose 2 electrons to become a proton H+
109
What is created from the movement of protons across the membrane by the electron transport chain?
creates a charge differential to synthesize ATP (ATP synthase)
110
What is ATP production dependent on?
(proportional) on the proton gradient (the energy)- more negative charge in the inner membrane, protons drive ATP production
111
What causes the protons in the inner membrane?
sourced through the chemical reactions in each phase of glucose metabolism: Free and tied to NADH (H+ carrier)
112
What is the final electron acceptor in the electron transport chain?
oxygen, to ultimately form water (H20).
113
What is the oxygen reduced to form?
Water (H2O)
114
What is the only part of the glucose metabolism that uses atomospheric oxygen?
final electron acceptor in the chain is oxygen, to ultimately form water. Atmospheric oxygen can move freely across the cell membrane
115
What is also being produced by the electron transport chain?
ATP
116
Where is ADP and ATP imported from?
The mitochondrial ADP/ATP carrier imports ADP from the cytosol and exports ATP from the mitochondrial matrix
117
What is Coenzyme Q?
ubiquinone: one of the transporters of protons across the mitochondrial membrane
118
Why impact does ATP have on the citric acid cycle?
Negative feedback-Regulator inhibitor enzyme
119
Why impact does ADP, AMP have on the citric acid cycle?
Positive feedback- Regulator activates enzyme
120
Glycolysis and gluconeogenesis serve ______- role
opposing
121
What are inhibitor enzymes of phosphofructokinase (PFK)?
ATP, citrate
122
What are activator enzymes of phosphofructokinase (PFK)?
AMP
123
What is another name of anaerobic metabolism?
Fermentation
124
What is important relationship of oxygen and glycolysis?
In the glycolysis stage (glucose breakdown to pyruvate does NOT require oxygen, albeit inefficient and low yield of energy
125
How many kilocalories for a glucose molecule?
24K calories (3%)
126
How is lactic acid formed?
formed from pyruvic acid with NADH)- some amount is always being made- diffuses into extracellular fluid and transported to liver.
127
When does lactic acid become a problem?
when it accumulates (acidosis and not sustainable source of energy
128
What is the formation of lactic acid known as?
Cori Cycle
129
Once _______ is restored, lactic acid restored to glucose in the liver
oxygen
130
What are two other fuel sources besides glucose?
Fatty acids and proteins
131
What are triglycerides hydrolyzed into?
into fatty acids and glycerol- transported to tissues
132
Where aren't triglycerides hydrolyzes?
brain and RBC’s
133
What is the process of beta oxidation (Fatty acids as fuel?
Degradation and oxidation to form Acetyl CoA to enter Kreb’s cycle with oxaloacetic acid
134
Where does beta oxidation?
Mitochondria
135
Glycerol also used in the _______ pathway
glycolytic
136
Fatty acids are polymers of ______
acetic acid
137
What forms acetoacetic acid?
In the liver Acetyl CoA
138
What is the byproduct of acetoacetic acid?
β-hydroxybutyric acid and acetone
139
What are ketoacidosis? Does this utilize glucose?
Ketoacidosis that results when accumulates in times of starvation (low carbohydrates source)- derived because you can not utilize glucose
140
What is the storage of lipids?
In contrast to glycogen, large amounts of lipids can be stored for energy (primary source when glucose not available). Higher ratio of C-O’s
141
Epinephrine and norepinephrine activate ______________
Lipase
142
What is the energy proceed from fatty acids in comparison of glucose?
Tremendous source of energy (150 x more than glucose (glycerol binds 14-18 carbon chains to make fatty acids)
143
What happens to excess Acetyl CoA?
produced by carbohydrates is formed into fatty acids in the cytosol (Acetyl CoA carboxylase)
144
Synthesis of fatty acids occurs _______ than degradation!
faster
145
What happens to excess carbohydrate consumption?
acts a fat-sparer (insulin) but converted to fat
146
What happens to excess amino acids?
excess are deaminated (oxidative process) to alpha keto acids + glutamic acid
147
What happens have amino acids are deaminated (2)?
Enter the Kreb’s cycle (produces less ATP than glucose), or released into bloodstream and picked up by adipocytes and converted to fat
148
What is ammonia converted to?
Ammonia resulting from the deamination process is converted to urea in the liver for excretion via kidneys
149
What is a byproduct of amino acid deaminated?
Ammonia
150
What happens to some amino acids?
Some amino acids break down to similar products that result from glucose or lipid metabolism
151
What are some amino acid that have importance in the kreb cycle?
alanine, cysteine, serine, glycine
152
What is deaminate alanine?
pyruvic acid
153
What is ketogensis?
Can be converted to glucose, glycogen or Acetyl CoA, which is polymerized to fatty acids
154
What is a ketone body?
2 molecules of Acetyl-CoA can condense to form acetoacetic acid
155
What spares protein metabolism?
Proteins are spared by carbohydrate and lipid metabolism - problem with starvation
156
What happens to amino acids in the absence of proteins?
body degrades 20-30 g/day of proteins for amino acids
157
What promotes protein synthesis (4)?
Growth hormone, insulin, testosterone, thyroid
158
What is glucocorticoids?
promote gluconeogenesis and the breakdown of fat and proteins for fuel
