Amino acids Flashcards
1
Q
What 2 amino acids are purely ketogenic?
A
- Leucine
- Lysine
2
Q
All amino acids except from one have both L and D configurations. What amino acid only has one configuration?
A
Glycine
3
Q
What are the 2 main basic amino acids - have a positive charge?
A
- Arginine (most basic)
- Lysine
- Also histidine, although only slightly so has no net charge at plasma pH
4
Q
What 2 amino acids are found in histones, which give them a positive charge?
A
- Arginine
- Lysine
5
Q
What are the 2 main acdic amino acids, have a negative charge as they donate H+ ions making solutions more acidic?
A
- Aspartate
- Glutamate
6
Q
What type of amino acids are commonly found in the lipid bilayer of cell membranes?
A
Hydrophobic
7
Q
What amino acids are swapped in sickle cell anemia?
A
Hydrophilic glutamate substituted for nonpolar/hydrophobic valine
8
Q
What amino acid has a rigid structure and is found in collagen?
A
Proline
9
Q
Are most amino acids glucogenic or ketogenic?
A
- Glucogenic OR glucogenic and ketogenic
10
Q
What can ketogenic amino acids not become?
A
Glucose
11
Q
What are ketogenic amino acids converted into?
A
Acetyl CoA
12
Q
What 2 amino acids are purely ketogenic?
A
- Lysine
- Leucine
Both essential
13
Q
What is the 1st step in phenylalanine metabolism?
A
Phenylalanine
-> Tyrosine
Enzyme: Phenylalanine Hydroxylase
14
Q
What substance acts as a cofactor for phenylalanine hydroxylase?
A
Tetrahydrobiopterin (BH4)
15
Q
What does Tetrahydrobiopterin lose and become when converting Phenylalanine into Tyrosine?
A
Dihydrobiopterin (BH2)
- Loses 2 Hs
16
Q
What enzyme and molecule converts Dihydrobiopterin (BH2) back to Tetrahydrobiopterin (BH4)?
A
Dihydrobiopteridine Reductase
- NADH
17
Q
What enzyme converts Phenylalanine
-> Tyrosine?
A
Phenylalanine hydroxylase
18
Q
What is classic PKU due to?
A
Phenylalanine hydroxylase deficient
19
Q
What other than defective Phenylalanine hydroxylase can cause PKU?
A
Defective / deficient BH4 cofactor
20
Q
What is the most common inborn error of metabolism?
A
Penylketonuria
21
Q
What are the signs/symptoms of PKU?
A
- Musty smell in urine from phenylalanine metabolites
- CNS symptoms - retardatio, sizures, tremor
- Pale skin, fair hair, blue eyes
22
Q
Why do those with PKU have pale skin, fair hair, blue eyes?
A
Lack of tyrosine conversion to melanin
23
Q
How is pku mainly treated?
A
Dietary modifactions
- Phenylalanine restricted - synthetic aa mixtures use for food
- Phenylalanine level monitored
- No aspartame
- Need to consume tyrosine
24
Q
Maternal PKU
A
Occurs in women w. PKU who consume phenylalanine
- High levels act as a teratogen
- Baby born w. microcephaly, congenital heart defects
25
When are babies screened for phenylalanine?
2-3 days after birth
| - Maternal enzymes may normalise levels at birth
26
What are causes of defective BH4 (causes ~ 2% of PKU)
- Defective dihydropteridine reductase
| - Also impaired BH4 synthesis
27
What other hormones are decreases in BH4 (deficiency other than phenylalanine)?
- Epinephrine, NE
- Serotonin
- Dopamine (thus increased prolactin)
28
How is BH4 deficiency treated?
- Dietary restriction of phenylalanine
- Supplementation of BH4
- L-dopa, carbidopa -> dopamine
- 5-hydroxytryptophan -> serotonin
29
What cofactor does tyrosine require?
BH4 (-> BH2)
30
What enzyme converts BH2 back to BH4?
Dihydropteridine Reductase
31
What molecule is used to convert BH2 back to BH4?
NADH (-> NAD+)
32
What enzyme does Metyrosine (a drug used for pheochromocytoma and hypertension) target?
Tyrosine Hydroxylase
| - Tyrosine not converted to DOPA
33
What enzyme converts Tyrosine to Dihydroxyphenylalanine?
Tyrosine Hydroxylase
34
What enzyme converts DOPA to Dopamine?
DOPA decarboxylase (removes carboxylic acid)
35
What vitamin acts as a cofactor for DOPA decarboxylase?
B6
36
What inhibits DOPA decarboylase periphally ?
Carbidopa
37
What comination therpay can be used in patients in parkinsons?
Levodopa/carbidopa
- Levodopa is a dopamine precursor
- Carbidopa prevents peripherally conversion of L-DOPA to Dopamine - reducing side-effects
38
What enzyme converts Dopamine to NE?
Dopamine B-hydroxylase
39
What vitamin acts as a cofactor for Dopamine B-hydroxylase?
Vitamin C
40
What enzyme converts NE to Epinephrine?
Phenylethanolamine N-methyltransferase
| - Adds methyl group
41
What acts as a cofactor for PNMT?
SAM (S-adenosyl Methionine)
| - Donates methyl groups
42
What is SAM synthesised from?
ATP and methionine (aa)
43
What is the difference in structure between methionine and homocysteine (very similar structures)?
SAM (w/o methyl group and adenosine)
44
What molecules are created from SAM when it removes its methyl group in the conversion of NE to E?
- Adenosine
| - Homocysteine
45
How is methionine regenrated?
Regenerated from homocysteine and N5-MethylTHF
- Makes Methionine (converted to SAM)
- and THF
46
What vitamins are required to make methionine and therefore SAM?
Folate (converted to N5-Methyl THF)
| - B12 acts as a cofactor for homocysteine to be converted to methionine (and N5-Methyl THF -> THF)
47
What is added to tyrosine (along with other steos to make Thyroxine)?
Iodine
48
What cells make melanin?
Melanocytes
49
What enzyme converts Tyrosine to DOPA quinone (which is then converted into melanin)?
Tyrosinase
50
What are the 2 main types of oculocutaneous albinism? and what causes them?
- OCA Type 1 - Tyrosinase deficiency-
| - OCA Type 2 - Tyrosine transporters
51
What are people with oculocutenous albinism at risk of?
- Sunburns, skin cancer
52
What is Chediak-Higashi Syndrome?
- Immunodeficiency
| - OCA type II: Transporter defect - MTs dysfunctional`
53
What does ocular albinism result in?
Ocular albinism
54
What is Tyrosine broken down into?
Homogentistic acid (HGA)
Then:
- Fumarate and (glucogenic)
- Acetoacetate (ketogenic)
By HGA Oxidase
55
What enzyme breaks down HGA into Fumarate and Acetoacetate?
Homogentistic acid Oxidase
56
How is alkaptonuria inherited?
AR
57
What is alkaptonuria a deficiency of?
Homogentistic acid oxidase
58
What molecule builds up in alkaptonuria and what does this result in?
Increased Homogentistic acid
- Polymerisation -> dark pigment
- Pigment deposited in connective tissue (ochronosis)
59
What are the findings in alkaptonuria?
- Dark urine when left standing (due to polymerisation), discolouration in infancy
- Arthritis (large joints, knees, hips)
- Black pigment in cartilage, joints
- X-ray: calcification of intervertebral discs
- Other symptoms later in life
60
How is alkaptonuria diagnosed?
- Elevated HGA in urine/plasma
61
How is Alkaptonuria treated?
Dietary restriction
| - Tyrosine an phenylalanine
62
What 2 enzymes break down catecholamines?
- Monoamine oxidase (MAO) Amine -> COOH
| - Catechol-O-methyltransferase (COMT): Methyl to O2
63
What are epinephrine and NE broken down into?
```
Vanillylmadelic acid (VMA)
- Excreted in urine
```
64
What is dopamine broken down into?
```
Homovanillic acid (HMA)
- Excreted in urine
```
65
How can pheochromocytoma be diagnosed?
Metanephrin and normetanephrine in 24 hour urine collection
OR 24 hr collection of VMAs in urine
66
How does Selegline work in Parkinson's?
MAO-b inhibitor
| - Increase Dopamine
67
How does Entacapone and tolcapone work in Parkinson's?
COMT inhibitors
| - Increase dopamine
68
What are MAO inhibitors such as Tranylcypromine and Phenelzine used for clinically?
Depression (less used nowadays)
| - Increase dopamine, NE and serotonin
69
What is Tyramine found in and what can Tyramine-rich foods cause in those on MAOi medications?
Cheese, red wine, some meats 'cheese effect'
Similar to dopamine
- Sympathomimetic
- Hypertensive crisis
70
What amino acid is used to synthesise serotonin?
Tryptophan
71
What is Tryptophan converted to first before being converted to serotonin (5-HT)?
5-Hydroxytryptophan
72
What enzyme converts Tryptophan to 5-Hydroxytrptophan (precursor of serotonin)
Tryptophan Hydroxylase
| - BH4 -> BH2
73
What is required as a cofactor for tryptophan hydroxylase?
BH4 (-> BH2)
74
What is carcinoid syndrome caused by?
GI tumours that secrete serotonin
75
Normally how much of tryptophan is converted to serotonin?
1%
76
how much of tryptophan is converted to serotonin in carcinoid syndrome?
Up to 70%
77
What molecule is depleted in carcinoid syndrome and what disease does this cause?
Tryptophan
| - Pellagra
78
What are the effects of serotonin?
- Diarrhea (serotonin stimulates GI activity)
- Increased fibroblast growth and fibrogenesis -> valvular lesions
- Flushing (other mediators also)
79
What valves may be affected in patients with carcinoid syndrome? (due to increased serotonin)
Tricuspid and pulmonary
80
What enzyme breaks down serotnin into 5-Hydroxyindole acetaldehyde?
MAO
81
What is serotonin broken down into?
5-Hydroxyindole acetaldehyde (MAO)
| -> 5-Hydroxyindoleacetic acid (5-HIAA)
82
What will be found in the urine in carcinoid syndrome?
5-HIAA
83
What are the symptoms of Pellagra?
- Hyperpigmented rash
- Exposed areas of the skin
- Red tongue (glossitis)
- Diarrhea and vomitting
- CNS: dementia, encephalopathy
- Dermatitis, diarhea and dementia
84
What vitamin deficiency can cause pellagra?
Niacin
85
What other than 5-HIAA can Serotonin be converted to?
Melatonin
86
What acts as a cofactor in the conversion of Tryptophan to Niacin?
B6
87
What is Niacin used to create?
NADH and NADPH
88
What is Hartnup disease?
AR
- Absence of transporter in PCT
- Loss of tryptophan in urine
- Symptoms of niacin deficiency
89
What is Histidine converted to Histamine by and what is a cofactor and what also is produced?
Histidine Decarboxylase
- Requires Decarboxylase
- CO2 produced in reaction
90
What is glycine (aa) required for?
Porphyrin ring - heme synthesis
91
What are the Carbons and nitrogens in heme from?
- Glycine
| - Succinyl CoA
92
What is arginine used to create?
Creatinine (muscles)
| Urea (urea cycle)
93
What amino acid and molecule does Nitric oxide synthase require?
Arginine and NADPH
To create Citrulline, Nitric oxide and NADP+
94
What is glutmate in the NS?
Excitatory NTs
95
What enzyme produces GABA from glutamate?
Glutamate Decarboxylase (B6 cofactor)
96
What are the branched chain amino acids (valine, leucine, isoleucine) broken down by (enzyme)?
a-ketoacid dehydrogenase
97
Where are branched chain amino acids (valine, leucine, isoleucine) broken down?
Muscle cells
98
What complex is a-ketoacid dehydrogenase a part of?
Branched-chain a-ketoacid dehydrogenase complex
99
What are the subunits in a-ketoacid dehydrogenase complex?
- E1: a-ketoacid dehydrogenase
- E2: dihydrolipoyl transacylase
- E3: dihydrolipoamide dehydrogenase
100
What are the cofactors for the a-ketoacid dehydrogenase complex?
- Thiamine
| - Lipoic acid
101
What are the 3 steps of branched cahin amino acid metabolism?
- Transamination
- Decraboxylation
- Dehydrogenation
102
What is Valine broken down into?
Succinyl CoA (glucogenic)
103
What is Isoleucine broken down into?
```
Succinyl CoA (glucogenic)
Acetyl CoA (ketogenic)
```
104
What is Leucine broken down into?
Acetyl-CoA
Acetoacetate
- Purely ketogenic aa
105
What is maple syrup urine disease due to a deficiency in?
A-ketoacid dehydrogenase
106
What will MSUD children have in their plasma?
- Increased branched chain AAs
| - And alpha-ketoacids in plasma
107
What gives MSUD patients urine a sweet smell?
Alpha-ketoacid of isoleucine (all 3 branched AAs have alpha-ketoacids after transamination)
108
What is the main problem in MSUD?
Neurotoxicity due to build up of leucine
109
What will the clinical symptoms of MSUD be?
1st few days of life
- Lethargy, irratibility
- Apnea, seizures
- Cerebral oedema
110
How can MSUD be diagnosed>?
Elevated valine, leucine and isoleucine in plasma
111
What is the treatment of MSUD?
- Dietary restriction of branched-chain amino acids
- Monitoring AA concentrations
- Thiamine supplementation
112
How is Homocysteine made?
Methionine and ATP create:
- SAM
SAM has adenosine and Methyl group removed to create:
- Homocysteine
113
What is the enzyme that converts Homocysteine and Serine into Cystathionine?
Cystathionine Synthase (B6)
114
What is cystathionine metabolised into?
- a-ketobutyrate -> Succinyl-CoA
| - Cysteine
115
What does cystathionine synthase require as a cofactor?
B6
116
What enzyme converts homocysteine back into Methionine?
Methionine synthase
117
What does Methionine synthase require as a cofactor?
B12
118
What is N5-methyl Tetrahydrogolate converted into by methionine synthase?
Tetrahydrofolate
119
What is a normal homocysteine level?
5-15 micromoles/L
120
What can cause mild-moderate elevations of homocysteine?
- B12/folate/B6 deficiecny
| - May be linked to increased risk of CV disease
121
What is considered severe hyperhomocysteinemia?
> 100umoles / L
122
What are the common symptoms of Homocystenuria?
- Retardation
- Lens discolouration
- Long limbs, chest deformaties
- Osteoperosis in childhood
- Blood clots
- Early atherosclerosis (stroke, MI)
123
What is classic Homocystinuria due to?
Cystathionine B synthase (CBS) deficiency
124
How is homocystinuria treated?
- Avoid methionine
- Increased cysteine (now essential aa)
- B6 supplements
125
What are other causes of Homocystinuria / elevations outside of CBS deficiency?
- Methionine synthase deficiency
| - Defective metabolism folate/B12 - MTHFR gene mutations
126
How are kidney stones in those with cystinuria prevented?
Methionine free diet
