Amino Acid Building Blocks Flashcards
Key regulatory molecules that control homeostasis, response to growth signals, initiate the ‘flight-or-fight’ response, and control circadian rhythms and movement
Neurotransmitters
There are three general classes of neurotransmitters, what are they?
Protein-based, steroid derived, and amino acid derived
The turnover of proteins yields amino acids, energy, nitrogen for various metabolites (porphyrins), and building blocks for the synthesis of
Neurotransmitters and nucleic acids
What is the chain reaction in Parkinson’s disease?
Loss of dopamine –> loss of norepinephrine –> loss of epinephrine –> loss of serotonin
Can result from reduced levels of dopamine
Schizophrenia
Seizures can be caused by deficiency of
GABA and dopamine
Causes hypersensitivity to sunlight, and increased incidence of retinal damage
Lack of Melanin
Neurotransmitters/regulators that are protein-based include
Insulin, growth hormone and endomorphins
The steroid-based neurotransmitters are
Estrogens and Androgens
Neurotransmitters that are synthesized from amino acids and related precursors include
Thyroxin, dopamine, norepi, and epi
Serotonin, melatonin and acetylcholine are also derivatives of
Amino acids
Catecholamine’s describe a set of neurotransmitters that are synthesized from
Tyrosine
A thyroid hormone that regulates metabolism and thermoregulation
Thyroxine
Higher levels of thyroxine increase
Protein synthesis
Three enzymes that facilitate thyroixine reactions all contain
Selenium
Which 4 neurotransmitters are derived from phenylalanine (with cofactor tetrahydrobiopterin)?
Thyroxine, dopamine, norepinephrine, and epinephrine
Regulates movement and promotes ‘reward-stimulating’ behavior.
-It stimulates the primary appetitive behaviors including feeding, fighting, fleeing and sexual function
Dopamine
Deficiency in dopamine synthesis can lead to
Parkinson’s Disease
There is evidence that ADD might also be associated with reduced levels of
Dopamine
In contrast, elevated levels of dopamine can cause schizophrenia. The key drugs that are used to treat schizophrenia depress
Dopamine levels
Important for stress-response. Synthesized and released from the adrenal medulla and plays a critical role in sympathetic neurons
Norepinephrine
It functions in the ‘fight-or-flight’ response by triggering glucose release and acceleration of heart rate
Norepinephrine
Norepinephrine is used as a vasopressor medication for treatment of
Hypotension
Low levels of norepinephrine can cause
Lethargy and depression
Conversion of norepinephrine –> epinephrine requires
SAM
Synthesized and released from the adrenal medulla. High levels are detected in the circulation following myocardial infarction
Epinephrine
Administered to treat cardiac arrest and anaphylaxis
Epinephrine
All contain two hydroxyls on the phenyl ring
Catecholamines
Tryptophan is an important amino acid for the synthesis of
Seratonin and melatonin
What is the co-factor for tryptophan?
Tetrahydrobiopterin
Important for thermoregulation and pain perception
Seratonin
When seratonin levels are misregulated, we can observe
Bipolar effects
Regulates the sleep/wake circadian cycle
Melatonin
Needed for synthesis of melanin pigment, which protects against sunlight induced UV damage
Tyrosine
Involved in the synthesis of prophyrin
Glycine
A co-factor in reactions leading from glycine –> prophyrin
Pyridoxial phosphate (Vit. B6)
Key component of creatine and porphyrin. Also required in the synthesis of creatine and glutathione
Glycine
Controls the primary inhibitory mechanisms in the brain
-synthesized from glutamic acid
GABA
Serves the primary role of attenuating neuronal function
GABA
Required for glutathione synthesis
Glutamate
Which 3 amino acids combine to make glutathione?
Glutamate, Cysteine, and Glycine
A free radical gas that can dilate blood vessels and lower blood pressure
Nitric Oxide (NO)
Which two things require arginine for synthesis?
NO and creatine
Histamine is a cyclic amine that is derived from
Histidine
Can regulate sleep; cause irritation of respiratory tract, and is released following tissue injury
Histamine
Histidine decarboxylase requires
Pyridoxal phosphate (Vit. B6)
Porphyria includes a number of disorders characterized by a defect in
Heme synthesis
Defects can arise from the transport and incorporation of iron, and in the synthesis of the
Porphyrin ring
Symptoms include photosensitivity, neurosensitivity, and a range of psychiatric conditions
Porphyrin deficiency
Heme synthesis initiates in a reaction that condenses Succinyl-CoA to
Glycine
Synthesis of heme begins in the mitochondria, continues in the cytosol, and is completed in the
Mitochondria
Phenylalanine –> Tyrosine is mediated by
-requires tetrahydrobiopterin as a cofactor
Phenylalanine hydroxylase
Tetrahydrobiopterin is restored by
Dihydropteridine reductase
Tyrosine –> DOPA is mediated by
-requires tetrahydrobiopterin as a cofactor
Tyrosine hydroxylase
DOPA –> Dopamine is simply a
-Requires B6
Decarboxylation of DOPA
The primary excitatory signal in the brain
Glutamate
A precursor for the synthesis of Glutathione, which is composed of a tripeptide (glutamate + cysteine + glycine), with a reactive sulfhydral group
Glutamate
A major antioxidant that is important for protecting RBC’s from oxidative damage
Glutathione
The RBC has a strongly oxidative environment and proteins that are damaged can precipitate into aggregates called
Heinz Bodies
Also plays an important role as a co-factor in the formation of accurate protein disulfide bonds
Glutathione
Uses NADPH to reduce and restore the levels of reduced glutathione
Glutathione Peroxidase
This enzyme is unusual in that it contains a modified amino acid, selenium, in its active site (selenocystine)
Glutathioneperoxidase
In erythrocytes the pentose-phosphate cycle keeps gluathione proxidase active by maintaining adequate supply of
NADPH
Also required for the movement of amino acids across membranes (termed the y-glutamyl cycle)
Glutathione
The recovery of amino acids by renal epithelial cells requires the
y-Glutamyl cycle
Movement of the amino acid results in the breakdown of glutathione into its amino acid constitutents (glutamate; cysteine; glycine), and therefore glutathione needs to be resynthesized in a mechanism that requires
ATP
The levels of glutathione are altered following prolonged oxidative stress and in
Diabetes
A storage form of high energy phosphate in tissues with high ATP requirements (muscle; brain)
Creatine
Creatine is synthesized from
Arginine and glycine
Creatine is synthesized from arginine and glycine and receives a methyl group from
SAM
Are highly cationic and can bind DNA. They are thought to mediate DNA specific reactions
Polyamines
Key messenger molecule (a reactive free radical), whose level is often altered in disease
NO
Synthesized from arginine in a reaction requiring NADPH and O2
NO
NO is generated by immune cells to induce macrophage-specific killing. NO also activates
Guanylate cyclase
Required in multiple reactions involving neurotransmitter synthesis
Tetrahydropterin
Recall that in PKU phenylalanine is not efficiently converted to tyrosine. This reaction requires the enzyme phenylalanine hydroxylase, and the co-factor
Tetrahydropterin
A product of this reaction is the synthesis of dihydrobiopterin, which must be converted back to tetrahydrobiopterin in a step that requires
GTP
This reaction is catalyzed by
-Requires NADH
Dihydropterin reductase
A progressive neurodegenerative disease with no cure. It results from the loss of dopamine producing cells (primarily the substantia nigra), which results in movement disorders, tremor and rigidity
Parkinson’s Disease
The disruption in dopamine synthesis is accompanied by deficiency in production of other
Catecholamines
The nigrostriatal pathway (extending from the substantia nigra to the striatum) produces about 75% of the brain’s
Dopamine
In PD as much as 80% of the dopamine producing cells degenerate before we see
Symptoms
What do we use to treat Parkinson’s?
L-DOPA
Its efficacy diminishes over time
L-DOPA
In the substantia nigra DOPA is converted to
Dopamine
Norepinephrine and epinephrine are broken down by the enzymes
Catecholamine O-methyltransferase (COMT) and by monoamine oxidase (MAO)
Can provide a way to increase the levels of these neurotransmitters for the treatment of clinical depression
COMT and MAO inhibitors
Lack of tyrosine reduces levels of
Catecholamne neurotransmitters
The high level of phenylalanine is converted to phenylacetate which combines with glutamine in the liver in
PKU
The resulting phenylacetylglutamine is directly excreted in the urine, and provides a method to eliminate two
Two nitrogens
Results from a deficiency in the conversion of tyrosine to melanin
Albinism
