Ch. 28-30

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1
What are the the 8 excitatory neurotransmitters?
 ,  ,  ,  ,  , ,  
What are the the 8 excitatory neurotransmitters?
Acetylcholine, aspartate, dopamine, histamine, norepinephrine, epinephrine, glutamate, 5‐ hydroxytryptamine (serotonin)
2
What are 3 inhibitory neurotransmitters?
1.  
2.  
3.  
What are 3 inhibitory neurotransmitters?
1. Glycine
2. Taurine
3. GABA
3
What are the 4 stages of neurotransmission?
1.  
2.  : Calcium activates the release of Ach on to Ach receptors. Binding of neurotransmitters causes depolarization (Na+/K+)
3.  : Metabolic degredation of Ach in synaptic cleft
What are the 4 stages of neurotransmission?
1. Resting
2. Excitation: Calcium activates the release of Ach on to Ach receptors. Binding of neurotransmitters causes depolarization (Na+/K+)
3. Termination: Metabolic degredation of Ach in synaptic cleft
4
In the case of neurotransmitter
 , it is taken up into  ,
before it is  
In the case of neurotransmitter
serotonin, it is taken up into presynaptic neuron (Reuptake),
before it is degraded
5
  are supporting, neuronal cells that maintains the normal
physiology of the nervous system
Glial Cells are supporting, neuronal cells that maintains the normal
physiology of the nervous system
6
Oligodendrocytes provide the   that insulate the axon.
Oligodendrocytes provide the fatty myelin
sheaths
that insulate the axon.
7
When the axonal connections die
off it results in  
(movement and balance
disruptions as well as vision
imbalance). (influenced by lack of  )
When the axonal connections die
off it results in Multiple Sclerosis
(movement and balance
disruptions as well as vision
imbalance). (influenced by lack of oligodendrocytes)
8
-Microglia protects the neuron from infection through phagocytosis. The microglia are activated by   inflammatory signals  
-The signals from the damaged cells include  
-Microglia protects the neuron from infection through phagocytosis. The microglia are activated by astrocyte inflammatory signals TNF-alpha, IL-6, and NO
-The signals from the damaged cells include ATP and CX3CL1
9
What is an example of something that is trans acetylated? What is the effect?
Histones. Acetylation if histones activates them.
10
 can be used in neurotransmitter synthesis.
Acetyl CoA can be used in neurotransmitter synthesis.
11
Acetylcholine causes the opening of
 channels in   nerve after a nerve stimulus
Acetylcholine causes the opening of
Na+/K+ channels in post synaptic nerve after a nerve stimulus
12
  is one of the fastest enzymes. Such a high turnover
is expected, since recovery from depolarization occurs within seconds.
Acetylcholinesterase is one of the fastest enzymes. Such a high turnover
is expected, since recovery from depolarization occurs within seconds.
13
choline goes to acteyl coline using  
choline goes to acteyl coline using choline acteyltrasnferase + CoA
14
acteylcholine is degraded and becomes   +   by a   reaction using  
acteylcholine is degraded and becomes choline + acetate by a hydrolysis reaction using cholinesterase
15
 ,  ,
 : competes with
acetylcholine receptor.
Tubocurarine, alpha‐bungarotoxin,
cobra toxin: competes with
acetylcholine receptor.
16
Physostigmine and neostigmine
inhibit   by
carbamoylating residue at
the active site.
Physostigmine and neostigmine
inhibit acetylcholinesterase by
carbamoylating serine residue at
the active site.
17
DIPF (organophosphate) reacts
with active site and
 modifies the enzyme.
DIPF (organophosphate) reacts
with active site serine and
covalently modifies the enzyme.
18
DIPF reacts with the active site serine and covalently modifies enzyme  
DIPF reacts with the active site serine and covalently modifies enzyme irreveseribly
19
Receptor targeted inhibitors (alpha bungartoxin, cobra toxin, etc) function as  
Receptor targeted inhibitors (alpha bungartoxin, cobra toxin, etc) function as comptetive inhibitors
20
  and  and have selenocystine
Glutathione peroxidase and deiodinase and have selenocystine
21
What is the universal methyl group donor?
SAM
22
Methionine is a   amino acid
Methionine is a conditional amino acid
23
Proline is synthesized from  
Proline is synthesized from glutamate
24
Glutamate becomes   using   and . It then forms a   intermediate. Using a   and  , it forms  .
Glutamate becomes glutamate semialdehyde using ATP and NADH. It then forms a gamma pyroline 5 carboxylate intermediate. Using a reductase and NADPH, it forms proline.
25
Hydroxylation of   occurs as a
posttranslational modification (hydroxylases
require   (ascorbate, lack of it
causes Scurvy).
Hydroxylation of proline occurs as a
posttranslational modification (hydroxylases
require Vitamin C (ascorbate, lack of it
causes Scurvy).
26
3‐hydroxyproline and 4‐hydroxyproline are
found in  .
3‐hydroxyproline and 4‐hydroxyproline are
found in collagen.
27
Glutathione peroxidase contains  
Glutathione peroxidase contains selenocysteine.
28
In the mRNA for selenoproteins, the codon  , which generally serves as a termination codon, codes for selenocysteine
In the mRNA for selenoproteins, the codon UGA, which generally serves as a termination codon, codes for selenocysteine
29
Selenocysteinyl-tRNA is added to ribosomes to make  
Selenocysteinyl-tRNA is added to ribosomes to make selenoproteins.
30
Selenocysteinyl tRNA is formed by adding   using ATP to  
Selenocysteinyl tRNA is formed by adding selenide using ATP to seryl-tRNA
31
3 examples of seleno proteins are  ,  , and  
3 examples of seleno proteins are glutathione peroxidase, deiodinase, and thioredoxin reductase
32
  is used to convert any hormone into more active form (i.e. T4 to T3).
Deiodinases is used to convert any hormone into more active form (i.e. T4 to T3).
33
Phenylalanine becomes  using   and   and  
Phenylalanine becomes tyrosine using phenylalanine hydroxylase and THB and O2
34
THB is formed using  and  
THB is formed using GTP and beneficial bacteria
35
The gene symbol for phenylalanine hydroxylase is  
The gene symbol for phenylalanine hydroxylase is PAH
36
PAH deficiency leads to classical  
PAH deficiency leads to classical PKU
37
PKU results in the accumulation of the products  ,  , and  
PKU results in the accumulation of the products phenylalanine, phenylpyruvate, and pheyllactate
38
PKU results in a   (core unique symptoms), light
pigmentation; peculiarities of
gait, stance, and sitting posture;
eczema; and epilepsy
PKU results in a mousy odor (core unique symptoms), light
pigmentation; peculiarities of
gait, stance, and sitting posture;
eczema; and epilepsy
39
PKU is an  
PKU is an autosomal recessive disorder
40
In PKU (PHU deficinecy), you would want to have low   and high   in the diet.
In PKU (PHU deficinecy), you would want to have low Phe and high Tyr in the diet.
41
In non-classical PKU, there are people who cannot make  
In order to fix this, take 
In non-classical PKU, there are people who cannot make biopterin supplement (THB)
In order to fix this, take Kuvan/sapropterin
42
Consumption of a Large numbers of neutral amino acids LNAA can also be used to address the  
Consumption of a Large numbers of neutral amino acids LNAA can also be used to address the non-classical pathway
43
Tyrosine becomes   which then can form  
Tyrosine becomes homogentistate which then can form fumarate and acetoacetate
44
Lack of   will cause   which is the build up of homogenistate
Lack of oxygenase will cause alcaptonuria which is the build up of homogenistate
45
Accumulation of
homogentisate, which upon
accumulation forms dark
brown polymer, gets
deposited into joints, causing
 
Accumulation of
homogentisate, which upon
accumulation forms dark
brown polymer, gets
deposited into joints, causing
arthritis
46
SAM is formed from  
SAM is formed from methionine
47
Methionine + ATP come together to form   using  
Methionine + ATP come together to form SAM using methionine adenosyltransferase
48
SAM is the main  
SAM is the main methyl trasnferase
49
Methyl Group Acceptor
Guanidoacetic acid

Methylated Product
 
Metabolic Pathway
 
Methyl Group Acceptor
Guanidoacetic acid

Methylated Product
Creatine phosphate
Metabolic Pathway
Creatine synthesis
50
Methyl Group Acceptor
Phosphatidyl ethanolamine synthesis

Methylated Product
 
Metabolic Pathway
 
Methyl Group Acceptor
Phosphatidyl ethanolamine synthesis

Methylated Product
Phosphatidyl choline
Metabolic Pathway
Phospholipid
51
Methyl Group Acceptor
Norepinephrine

Methylated Product
 
Metabolic Pathway
 
Methyl Group Acceptor
Norepinephrine

Methylated Product
Epinephrine
Metabolic Pathway
Catecholamine
52
Methyl Group Acceptor
rRNA & tRNA

Methylated Product
 
Metabolic Pathway
 
Methyl Group Acceptor
rRNA & tRNA

Methylated Product
Methylated RNA
Metabolic Pathway
RNA synthesis
53
Methyl Group Acceptor
Protein bound lysine

Methylated Product
 
Metabolic Pathway
 
Methyl Group Acceptor
Protein bound lysine

Methylated Product
Trimethyl lysine
Metabolic Pathway
Carnitine synthesis
54
Methyl Group Acceptor
Histones (Chromatin)

Methylated Product
 
Metabolic Pathway
 
Methyl Group Acceptor
Histones (Chromatin)

Methylated Product
Methyl Lys or Arg of histones
Metabolic Pathway
Chromatin Modelling
55
Methyl Group Acceptor
DNA

Methylated Product
 
Metabolic Pathway
 
Methyl Group Acceptor
DNA

Methylated Product
CpG islands
Metabolic Pathway
Gene Expression
56
 : (Many Proteins at the
Amino Terminal end residues such as
Met, Ser, etc…
N‐Acetylation: (Many Proteins at the
Amino Terminal end residues such as
Met, Ser, etc…
57
 : (Histones on Lys and
Arg Residues)
N‐Methylation: (Histones on Lys and
Arg Residues)
58
 : (Histones on Lys
Residue)
N‐Ubiquitination: (Histones on Lys
Residue)
59
 : (Histones on
Serine Residues) -> adds potential energy to a protein
O‐Phosphorylation: (Histones on
Serine Residues) -> adds potential energy to a protein
60
Histones are methylated on   and 
Histones are methylated on lysine and arginine
61
Methionine + ATP is converted to SAM using  . SAM transfers a methyl and becomes  . From that step,  forms. From there,   +   forms cystathionine. Gamma cystathionase + B6 then forms   +   (can then become  )
Methionine + ATP is converted to SAM using MAT (methionine adenosyltransferase) . SAM transfers a methyl and becomes S-adenohomocysteine. From that step,homocysetine forms. From there, cystathionine B-synthase + vitamin B6 forms cystathionine. Gamma cystathionase + B6 then forms cysteine + alphaketobutyrate (can then become propinoyl CoA)
62
Defect in cystathionine synthase, results in
the accumulation of   and
  in the blood and  
in the urine. Symptoms include skeletal abnormalities,
thrombosis and mental retardation.
Defect in cystathionine synthase, results in
the accumulation of homocysteine and
methionine in the blood and homocystine
in the urine. Symptoms include skeletal abnormalities,
thrombosis and mental retardation.
63
Problems with the enzyme  ,  ,   or addition of   causes homocystinuria.
Problems with the enzyme cystathionine B-synthase, vitamin B6, vitamin B12 or addition of serine causes homocystinuria.
64
Problems with the enzyme   or   causes cystathionuria
Problems with the enzyme gamma cystathionase or vitamin B6 causes cystathionuria
65
To make succinyl CoA from propinoyl COA is done using  and  
To make succinyl CoA from propinoyl COA is done using methyl malonyl mutase and B12
66
To regenerate methionine from homocystesine, you need  ,  , and  
To regenerate methionine from homocystesine, you need methione synthase, B12, and N5-CH3-THF
67
In the regeneration of methionine from homocystine can have a methyl group donated from either a   or  
In the regeneration of methionine from homocystine can have a methyl group donated from either a serine or glycine
68
Only 2 enzymes require B12 as cofactor:   and  
Only 2 enzymes require B12 as cofactor: methionine synthase and methyl malonate mutase
69
Sulfur amino acids can oxidize two cysteines to make a disulfide bond
(between 2 cysteines makes  , 2 homocysteines become  )
Sulfur amino acids can oxidize two cysteines to make a disulfide bond
(between 2 cysteines makes cystine, 2 homocysteines become homocystine)
70
-Cystinuria: Defect in membrane transport of
  through epithelial cell
-Cysteine gets oxidized to  which has poor
solubility and it precipitates in the urinary tract
and forms  .
-Cystinuria: Defect in membrane transport of
dietary cysteine through epithelial cell
-Cysteine gets oxidized to cystine which has poor
solubility and it precipitates in the urinary tract
and forms kidney stones.
71
Homocysteine can form homocysteinethiolactone. This is a reactive intermediate that  
which aggregates and eventually forms  .
Homocysteine can form homocysteinethiolactone. This is a reactive intermediate that thiolates LDL
which aggregates and eventually forms atheromas.
72
Tryptophan degradation gives you   as a byproduct and   and   as products
Tryptophan degradation gives you formate as a byproduct and glutarate and niacin (B3) as products
73
Valine and Isoleucine are broken down into   (which then becomes   that can enter  ). Leucine becomes  because it is  .
Valine and Isoleucine are broken down into propinoyl coa (which then becomes succinyl CoA that can enter TCA). Leucine becomes acteyl CoA because it is ketogenic.
74
The enzyme used to break down valine, isoleucine, and leucine is 
The enzyme used to break down valine, isoleucine, and leucine is BCAA dehydrogenase
75
BCAA dehydrogenase reqires  
BCAA dehydrogenase reqires thiamin (B1), lipoic acid, CoA (B5), riboflavin B2, and Niacin B3
76
Maple Syrup Disease
Symptoms: Urine has maple syrup odor, vomiting, brain damage
Treatment: Reduced   in diet
Type of disorder:  
Maple Syrup Disease
Symptoms: Urine has maple syrup odor, vomiting, brain damage
Treatment: Reduced branched chain amino acids in diet
Type of disorder: Autosomal recessive
77
Propinoyl CoA makes  ,  ,  , and   on being degraded.
Propinoyl CoA makes methionine, threonine, isoleucine, and valine on being degraded.
78
Methylmalonic acidemia is a deficiency in  or  . Causes metabolic acidosis and mental retardation.
Methylmalonic acidemia is a deficiency in methyl malonyl CoA mutase or vitamin B12. Causes metabolic acidosis and mental retardation.
79
Histidine breaks down into  and   from   using  
Histidine breaks down into glutamate and N-Foramino THF from N-foramino gultamate using THF
80
The enzyme histidase is highly expressed in   and  . In skin,
 is one of the components of  .
The enzyme histidase is highly expressed in skin and liver. In skin,
urocanate is one of the components of sweat.
81
Lysine is   to form   (required for   of fatty acids)
Lysine is trimethylated (3 SAM) to form carnitine (required for B oxidation of fatty acids)
82
Phosphocreatine is an  
Phosphocreatine is an energy storage molecule
83
Glycine + Arginine yields   and with   becomes   which then forms   using  
Glycine + Arginine yields Guanidinoacetate and with SAM becomes Creatine which then forms Phosphocreatine using ATP
84
What are the 3 componenents of folic acid (vitamin B9)?
1. Pterydine ring
2. PABA
3. Polyglutamate
85
Microorganisms converts   and  
into folic acid. Humans  
synthesize folic acids. Folic acid is an
 .
Microorganisms converts pteridine
precursors
and para‐aminobenzoic acid
into folic acid. Humans cannot
synthesize folic acids. Folic acid is an
essential vitamin.
86
Folic acid synthesis is inhibited by
 (anti microbial agent).
Folic acid synthesis is inhibited by
sulfonamides (anti microbial agent).
87
Methotrexate blocks dihydrofolate reducatse from   to 
Methotrexate blocks dihydrofolate reducatse from DHF to THF
88
THF is a   carbon carrier
THF is a one carbon carrier
89
What is the folate trap?
Responsible for trapping   in the  
What is the folate trap?
Responsible for trapping folic acid in the N5 methyl THF form
90
The folate trap leads to insufficent formation of   due to  
The folate trap leads to insufficent formation of methionine due to B12 deficiency
91
The folate trap leads to inhibition of   which does conversion of   to  . Inhibition causes  .
The folate trap leads to inhibition of thymidylate synthase which does conversion of dUMP to dTMP. Inhibition causes slowed cell division .
92
Serine + THF produces  
Serine + THF produces glycine + N5-N10-Methylene THF
93
Glycine produces
1.  
2.  
3.  
4.  
5.  
Glycine produces
1. Heme
2. Serine
3. Purine
4. Collagen
5. One carbon donors
94
Taurine is produced from 
Taurine is produced from cysteine
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