Minerals

Minerals:

Fe²⁺

Hemoglobin → O2 Transport

Supports electron transport chain → Complex III/IV

When decreased = Possible mental retardation in children

Ca²⁺

Necessary for muscle contraction

o       All muscles need INTRACELLULAR Ca²⁺

o       Cardiac & Smooth Muscle need EXTRACELLULAR Ca²⁺

Needed for atrial contraction

IP3/DAG Second messenger system

Mg²⁺

Co-factor for ALL KINASES and PTH

Cu²⁺

Need for the hydroxylation of lysine

Deficiency

o       Minkys kinky hair

Orange hair

Feels like copper wiring

Excess = Wilsons Disease = hepatolenticular degeneration

o       Lenticular → Basal ganglia

o      

Trace Elements: Chromium - neede in Insulin action Selenium - necessary for heart Manganese - xanthine oxidase

Hepato → liver

o       Keisher-fleisher rings in iris

o       Ceruloplasmin deficiency

Zn

Hair, taste buds, dysgusia, sperm

Biochemistry:

CONCEPT:

Low Energy State= the default illness state affecting all organ systems.

• Organs:
• CNS mental retardation
• Muscle weakness
• CV Heart Failure
• Cilia Respiratory infection, shortness of breath
• GI diarrhea initially due to malabsorption, then followed by constipation due to lack of motility
• Hair falls out
• Cuticles brittle
• Skin dry
• Vascular endothelium breaks down
• Bone marrow:
• RBC anemia
• WBC agranulocytosis
• Platelet bleeding disorder
• Renal Proximal convoluted tubules
• Reproductive low sperm count
• Bladder slows down → hemorrhagic cystitis
• Endometrium no menstruation
• Germ cells CA
• Signs and Symptoms:
• Most Common Symptom = weakness and SOB
• Most Common Sign = Tachypnea and Dyspnea
• Most Common infection = UTI and respiratory infections
• Most Common cause of death = Heart Failure

Proteins:

Body is made up of mostly proteins.

o       Recall that enzymes are proteins

But body likes to hang on to FAT (9 Kcal/1g)

SUGARS and AMINO ACIDS (4 kcal/ 1g)

Structure of Amino Acids: Exception: Proline:

NH₃ COOH NH₂ COOH

Amino Acid Imino

Imino group creates kinks and bends Found in: hair, muscle, skin, collagen, cartilage,

R

(determines structure of AA)

Every acid group starts without a charge. Ex:  As an amino acid group dissociates it becomes less soluble and more bioavailable.

Buffers:

Proteins are the most important intracellular buffers

Bicarbonate is the most important extracellular buffer

Dissociation= loss of H+

Soluble = has charge and will attract H₂O → Can not cross Blood Brain Barrier

Bioavailable = neutral, can cross a fat soluble membrane.

o       When talking about Bioavailability think about Volume of distribution or t

Example:

NH₃⁺ → NH₂ = ↓ Solubility (by losing a charge); ↑ Bioavailability (by making it neutral)

COOH → COO^- = ↑ Solubility (by adding charge); ↓ Bioavailability (b/c no longer neutral)

pKa:

1 2 3 4 5 6 7 8 9 10 11 14

Titration Curve:

Histadine has pK = 6.7 which is closest to pH of 7.4 it is the best buffer in humans.

	* Liver handles fat-soluble content

Dissociation relationship:

pH = pK + 2 99% dissociated =99% soluble 1% bioavailable

pH = pK + 1 90% dissociated =90%soluble 10% bioavailable

pH = pK 50% dissociated Best Buffer

pH = pK - 1 10% dissociated =10% soluble 90% bioavailable

pH = pK - 2 1% dissociated =1% soluble 99% bioavailable

In order to absorb molecules they need to remain neutral = bioavailable. Follow these rules to keep molecules neutral.

To absorb more acid need to place in a stronger acid

o       Acid + Strong Acid = Behaves as a BASE

To absorb more base place in a stronger base

o       Base + Strong Base = Behaves as a ACID

Understand that the body makes 20x more HCO₃^- than acid

o       Because we ingest primarily acidic substances

Example:

1. Crossing the Blood Brain Barrier need to remain neutral.
2. If ingest acid need to keep it charged so it will not be absorbed give base (NaHCO₃)
1. Recall Activated Charcoal in the ER
3. If ingest base keep charged by giving acid (coke, juice) will absorb less base.
4. Patient taking Aspirin and eating acidic food can cause increased dissociation of ASA and then ASA poisoning.

Common Acids: ASA, Myoglobin (d/t crush injury), phenobarbiltal. Common Bases: Amphetamines

Common pHs:

Stomach pH = 1-2

Duodenum pH = 3-5

Early Jejunum pH = 5-7

Late Jejunum pH = 7-9

Ileum pH > 9

Example: ASA has pK = 4.3 (like other NSAIDs), therefore it would be absorbed best in stomach pH of 1-2, when 1% will be dissociated and 99% will be bioavailable for absorption.

Key Concept: Acid + Base will decrease absorption.

Example: When muscle breaks down releasing myoglobin, give bicarbonate to prevent secretion and further loss of myoglobin.

pI = pk1 + pK2 2

Isoelectric Point:

pI = Zwiterion = NO NET charge.

When you have more than two groups:

o       like groups will have isoelectric point that will balance out opposite like group isoelectric point.

Gel Electrophoresis

Cathode is where cations GO

Anode is where anions GO

Amino Acids:

Groups

Acidic Groups = Asp, Glu

Basic Groups = Arg, Lys

Sulfur = Cys, Met

O-Bonds = Ser, Thr, Trp

N-Bonds = Asp, Gln

Branched aa = Leu, Ile, Val

Bulky (aromatic) =Phe, Thr, Trp

Small =Gly

Kinky =Pro

Ketogenic = Lys, Leu

(made and broken down to acetyl Co-A)

Glucogenic + Ketogenic = Phe, Iso, Thr, Trp

Glucogenic = All the rest.

GABA is a suppressor causing: Bradycardia, Lethargy, Constipation, Impotence

GABA concept:

Essential Amino Acids:

Body will break down protein to look for essential amino acids if not provided by the diet.

PVT TIM HALL

Phenylalanine

Valine

Tryptophan

Threonine

Isoleucine

Methionine

Histidine

Arginine

Leucine

Always guess Autosomal recessive.

Lysine

Childhood screening: PKU, galactosemia, hypothyroidism, congenital adrenal hypoplasia, biotindase.

Disorders:

• PKU:
• Phenylalanine hydroxylase is deficient
• It is needed to make tyrosine
• Therefore Tyrosine becomes an essential amino acid.
• Signs and Symptoms:
• Tyrosine is used to make:

Dopamine, Epinephrine and Norepinephrine mental retardation

• PKU cont.

Melanin for pigment pale, blond, blue eyes

Build up of phenylacetate + phenylpyruvate = musty odor

Screened in childhood GUTHIRE testing.

• Maple Syrup Urine Disease:
• Deficiency in branched amino acids → Leu, Iso, Valine
• Defective transport of branched amino acids in kidney collecting ducts will cause amino acids to leak out.

• Cystinuria: Autosomal Dominant
• Cystathione synthase enzyme is missing.
• 4 Amino Acids show up in Urine
• Cysteine
• Ornithine
• Lysine
• Arginine
• Develop Cysteine stones that have a crystal/envelope shape.

Protein Structure:

L R R NCNC R Transfiguration

1 AA sequence including the peptide bonds:

All Bonds are planar = flat

Restricted mobility

R groups face away from each other

2 a-helix vs. b- pleated sheet

Proline

			Humans have L-amino acids will attack the D-amino acids Adipose layers have the least amount of blood supply will take longer to heal.

GI, vessels, hair flat bones, skin

3 3D- determined by:

Hydrophobic

Hydrophilic interactions.

Covalent bonds begin to form.

Ex. Hemoglobin

4 2 proteins interact with enzymes

Cooperativity

Allosterism (one site will affect another site)

HEMOGLOBIN

	Vm
					[S]
				Allosterism

• The most effective way to monitor drug intake → PEAK & TROUGH Measurements
• Peak → taken 4 hours after dose → If Peak is ↑↑ = the dosage is too high
• Trough → taken 1 hour after dose → If Trough is ↑↑ = Give the drug less often

	Meds: usually exhibit 1st order kinetics As [drug], degradation T less toxic Chemo drugs exhibit 0 order kinetics Same amount of drug metabolized over time regardless of concentration T more toxic

Acid Hydrolysis:

• Dip protein in acid acid denatured protein.

o       Glutamine glutamate

o       Aspargine aspartate

Gel Electrophoresis:

• Separated protein based on size

o       Smallest will move the farthest

o       Then separate by charge.

Ninhydrin Reaction:

• Separate out proline

o       Proline will stain yellow

o       All others will stain purple.

Edmunds Degradation

• Degradation that needs Propylisothiocyanate (PITC)

o       Will react with one amino acid at a time

o       From the L amino terminal

o       Used in spectrophotometry

o       Good for only 100 amino acids.accuracy

Restriction Peptidase:

Amino Acids Sequencing

_ _ _ _ _

(lys, ala)  (ser, met, phe)

You need to know which was amino acid was sequenced first!!!

If you cut with trypsin, where does it cut?

Trypsin cuts to the RIGHT of of lys and arginine!!!

_ lys/___ = Therefore, in a question, find the answer that already contains lys in the second position

KNOW WHERE THE ENZYME CUTS

Restriction Peptidases:

ALL CUT TO THE RIGHT

• Trypsin I - cuts arginine or lysine ( basic groups)
• Elastase - gly, ala, ser
• CNBr - met
• Amino peptidase - repeatedly cleaves N-terminal from glycopeptides
• Chymyotrypsin - phe, thr, trp
• Mercaptoethanol - dissolves disulfide bonds

EXCEPTION:

Carboxy peptidase - cuts to the LEFT of any amino acid on carboxy terminal

Allosterism

• Rate limiting Enzyme

o       Always the slowest

Inhibition:

o       Competitive vs. Non-Competitive.

Competitive looks like substrate fights for active site

V_max = V_max

Non-competitive competing for regulatory site.

o       No D in K_m or affinity

o       V_max

Competitive vs. Non Competitive inhibitors: