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

Production of Dopamine

Connections between low norepinephrine levels and dopamine levels

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?

Neurotransmitters in Epilepsy

• Serotonin

• Acetylcholine

• GABA

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

Results of Insulin Deficiency8

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

HC HC

HC

HCHC

HC B12

B12

B12

B12B12

B12

HC B12HC B12

HC B12

HC B12 HC B12

HC B12

HCIF B12

Stomach

Small Intestine