57 - Synthesis of Nitrogen compounds

Other N2 containing compounds

• Porphyrins (heme)

• Neurotransmitters

• Hormones

• Purines

• Pyrmidines

Sources of input for the AA pool

1. Dietary proteins (100g/day)

2. Degredation of BPdy proteins (400g/day)

3. Amino Acid Synthesis de novo (NEAA)

Fates of output from the AA pool

1. Synthesis of proteins

2. Catabolism into CO2 + H2O + NH3

3. Synthesis of other N2 containing compounds (30 - 40g/day)

Nitrogen Balance

balance of (N_in - N_out) in a 24 hour period

determined by : protein intake (g) /6.25-(UUN + 4g)

UUN = urinary loss

Positive N2 balance

When intake > excretion

Occurs during tissue growth (pregnancy, childhood, recovery from illness)

Negative N2 balance

When intake < excretion

Associated with inadequate dietary protein, lack of essential AAs or physiologic stress

Steps of chemical communication

1. Signal production and release

2. Signal Reception

3. Signal transmission and amplification

4. Response

Catecholamines

Dopamine, Epinephrine, Norepinephrine

Location of Dopamine production

Presynaptic Neurons

Location of Dopamine storage

Vesicles

Location of Epinephrine and Norepinephrine production

Adrenal medulla

Tyrosine

Precursor of Catecholamines

Tyrosine Hydroxylase

Rate-limiting step of Catecholamine synthesis

Tetrahydrobioprotein - BH4

• Coenzyme required for step 1 of Catecholamine synthesis, which makes L-DOPA

  • Synthesized from GTP

Pyridoxal Phosphate (PLP)

• Coenzyme required for step 2 of Catecholamine synthesis, which makes dopamine

  • decarboxylation rxn

Ascorbate (Vit C) and Copper

• Coenzymes required for step 3 of Catecholamine synthesis, which makes norepinephrine

Catecholamine Synthesis overview

L-Tyrosine → L-Dopa → Dopamine → Norepinephrine → Epinephrine

Parkinson Disease

• Neurodegenrative movement disorder due to insufficient dopamine production due to loss of dopamine producing cells in the brain

Levodopa (L-DOPA)

most common treatment for parkinsons

Carbidopa

Treatment for parkinsons

inhibits the enzyme converting L-DOPA to dopamine in the peripheral nervous system. It cannot cross the blood–brain barrier, and when used in tandem with L-DOPA, it allows more peripheral L-DOPA to cross the BBB in order to reach a more therapeutic range in the CNS

MAO

degrades neurotransmitters in their first reuptake into vesicles of the presynaptic neuron via oxidative deanimation

• degrades 50% of catecholamines

COMT

degrades neurotransmitters in their second reuptake into the effector cell

MAO inhibitors

used as antidepressants and treatment of some neurologic disorders: Result in increased levels of NTs in the
presynaptic neurons

Tryptophan

Precursor of Serotonin

PLP and BH4

coenzymes needed in Serotonin synthesis

Termination of Serotonin

• Re-uptake into the neuron by SERT

• MAO

Implications of serotonin

• regulation of sleep, cognitive function, and mood

• Activates reflexes in GI

• Precursor for melatonin

SSRIs

result in higher levels of serotonin in the synaptic
space.

“Designer drugs”

work through serotonin-containing neurons

Histidine

Precursor of Histamine

PLP

only coenzyme required for Histamine synthesis

Implications of Histidine

• regulation of food and water intake

• autonomics

• brain functions such as learning and memory

• allergic and inflammatory mediator

• does not cross the blood brain barrier

Arginine

Precursor of NO synthesis

Nitric Oxide Synthase (nNOS)

Enzyme of NO Synthesis in neurons (is Ca++ dependent)

iNOS

Enzyme of NO Synthesis in immune cells (is NOT Ca++ dependent, but IS inducible by cytokines)

eNOS

Enzyme of NO Synthesis in endothelial cells (is Ca++ dependent)

Phosphocreatinine

A high energy phosphate molecule that can reversibly transfer the
phospho group to ADP to produce ATP found in brain, skeletal, and muscle cells

Synthesis of creatine phosphate

• Begins in the kidney,

• then in liver

• Phosphorylation step - in the respective tissue (brain, heart, skeletal muscle) by Creatine (phospho) kinase (CPK or CK) (reversible step)

Degradation and excretion of Creatine Phosphate

• Spontaneous cyclization to creatinine

• Rapidly cleared from the blood and excreted in the urine via the kidney

increased blood creatinine levels

indicator of kidney dysfunction

increased levels of creatinine

used as diagnostic measure of muscle loss