exam 3 review i 1. parkinson’s disease; dopamine biosynthesis, cofactors 2. biochemistry of...
TRANSCRIPT
Exam 3 Review I
1. Parkinson’s disease; dopamine biosynthesis, cofactors2. Biochemistry of Epilepsy; neurotransmitters3. Type 1 Diabetes; hypothesis4. PKU; Phe->Tyr5. Pernicious Anemia; B12
Connections between low norepinephrine levels and dopamine levels
1. Dopamine is a precursor to both Catecholamines, Norepinephrine and Epinephrine.
2. Dopamine + Dopamine Beta Hydroxylase & Vitamin C -> Norepinephrine
3. Norepinephrine + Phenylethanolamine N-Methyltransferase & S-Adenosyl Methionine with Cortisol -> Epinephrine
DBH
PNMT
Vit. C
Dopamine
Norepinephrine
Cortisol SAMe
Epinephrine
Dopamine-Motor Control
-Lack of Dopamine => Loss of motor activity
Norepinephrine/Epinephrine-Excitatory Neurotransmitters / Hormones
-Increase heart rate-Increase fight or flight response-Increase awareness and alertness
Connections between low norepinephrine levels and dopamine levels
Why do we care about low levels of norepinephrine?
Formation of Serotonin
• Synthesis from Tryptophan Central Nervous System
– Regulation of mood, appetite, sleep, and muscle contraction
– Modulation used in antidepressants
Themedicalbiochemistrypage.org
Formation of GABA
• Synthesis from Glutamine• Central Nervous System
– Inhibitory Neurotransmitter– Cause Hyperpolarization
Themedicalbiochemistrypage.org
Population Affected
• Type I Diabetes is most prevalent in Finland, Sardinia, Scandinavia, and Scotland
• Extremely uncommon in Asian countries3
• White Americans are 1.5 times more likely to have diabetes than black or Hispanic Americans
• Males are at greater risk in regions of high incidence8
• Increased incidence in winter monthsLack of vitamin D is a potential environmental trigger3
Risk increases as you move away from the equator
Hypothesis
• Type 1 Diabetes is an autoimmune disease: 1) A T1D susceptible gene is present2) A mutated MHC protein is produced 3) An environmental trigger causes the MHC to function improperly4) An autoimmune response destroys the beta cells of the pancreas5) Insulin is no longer produced
Phenylalanine
• Essential Amino Acids
cannot be derived from anabolic processes in the body and must be
consumed in the diet: F, L, I, V, M, T, W
Wikipedia.com
Phenylalanine-Biochemistry
Cofactor (BH4) aided catalysis
Essential amino acid Phe is converted to Tyr with the cofactor BH4, O2, and PAH
Biocyc.org
PAH
PKU-Impact and distribution
Unequal geographical distribution
Incidence of PKU is caucasians is 1 in 10,000 to 15,000
Williams et al 2008 Adapted from Scriver and Kaufman 2001
Region / Country Incidence of PKUAsian Populations China 1 : 17,000Japan 1 : 125,000European PopulationsTurkey 1 : 2,600Yemenite Jews (in Israel) 1 : 5,300Scotland 1 : 5,300Czechoslovakia 1 : 7,000Hungary 1 : 11,000Denmark 1 : 12,000France 1 : 13,500Norway 1 : 14,500United Kingdom 1 : 14,300Italy 1 : 17,000Canada 1 : 22,000Finland 1 : 200,000Arabic Populations Up to 1 : 6,000Oceania Australia 1: 10,000
Our 2 Biological Molecules
• Vitamin B12(Cobalamin)
• Intrinsic Factor
http://www.chem.uky.edu/research/daunert/Daunert%20Research%20Group%20Website/Binding%20Proteins.htm
http://www.google.com/imgres?imgurl=http://www.pnas.org/content/104/44/17311/F2.large.jpg&imgrefurl=http://www.pnas.org/content/104/44/17311/F2.expansion.html
Vitamin B12 Continued…
– Vitamin B12 is a cofactor for:
• Isomerases• Methyltransferases• Dehalogenases
– Takes part in DNA synthesis, methylation and neuron function
Sources: Voet