Hemoglobin → O2 Transport
Supports electron transport chain → Complex III/IV
When decreased = Possible mental retardation in children
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
Co-factor for ALL KINASES and PTH
Need for the hydroxylation of lysine
o Minky’s kinky hair
Feels like copper wiring
Excess = Wilson’s Disease = hepatolenticular degeneration
o Lenticular → Basal ganglia
Elements: Chromium - neede
in Insulin action Selenium -
necessary for heart Manganese -
Chromium - neede in Insulin action
Selenium - necessary for heart
Manganese - xanthine oxidase
o Keisher-fleisher rings in iris
o Ceruloplasmin deficiency
Hair, taste buds, dysgusia, sperm
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,
Imino group creates kinks and bends
Found in: hair, muscle, skin, collagen, cartilage,
(determines structure of AA)
(determines structure of AA)
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 ½
NH3+ → NH2 = ↓ Solubility (by losing a charge); ↑ Bioavailability (by making it neutral)
COOH → COO- = ↑ Solubility (by adding charge); ↓ Bioavailability (b/c no longer neutral)
1 2 3 4 5 6 7 8 9 10 11 14
Histadine has pK = 6.7 which is closest to pH of 7.4 it is the best buffer in humans.
* Liver handles fat-soluble
* Liver handles fat-soluble content
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
Acids: ASA, Myoglobin (d/t crush
injury), phenobarbiltal. Common Bases:
Common Acids: ASA, Myoglobin (d/t crush injury), phenobarbiltal.
Common Bases: Amphetamines
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
pI = pk1 + pK2
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.
Cathode – is where cations GO
Anode – is where anions GO
Acidic Groups = Asp, Glu
Basic Groups = Arg,
Sulfur = Cys, Met
O-Bonds = Ser, Thr, Trp
N-Bonds = Asp, Gln
Branched aa = Leu, Ile, Val
Bulky (aromatic) =Phe, Thr, Trp
(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 is a suppressor causing:
Bradycardia, Lethargy, Constipation, Impotence
Essential Amino Acids:
Body will break down protein to look for essential amino acids if not provided by the diet.
PVT TIM HALL
Always guess Autosomal recessive.
Always guess Autosomal recessive.
Childhood screening: PKU, galactosemia, hypothyroidism, congenital adrenal
PKU, galactosemia, hypothyroidism, congenital adrenal hypoplasia, biotindase.
Dopamine, Epinephrine and Norepinephrine mental retardation
Melanin for pigment pale, blond, blue eyes
Build up of phenylacetate + phenylpyruvate = musty odor
Screened in childhood GUTHIRE testing.
L R R N—C—N—C R Transfiguration
All Bonds are planar = flat
R groups face away from each other
2 a-helix vs. b- pleated sheet
Humans have L-amino
will attack the D-amino acids Adipose layers have the least
amount of blood supply
will take longer to heal.
Humans have L-amino acids à 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:
Covalent bonds begin to form.
Allosterism (one site will affect another site)
Vm [S] Allosterism
exhibit 1st order kinetics Chemo drugs exhibit 0 order
kinetics Same amount of drug
metabolized over time regardless of concentration T
Meds: usually exhibit 1st order kinetics
Chemo drugs exhibit 0 order kinetics
Same amount of drug metabolized over time regardless of concentration T more toxic
o Glutamine glutamate
o Aspargine aspartate
o Smallest will move the farthest
o Then separate by charge.
o Proline will stain yellow
o All others will stain purple.
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
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
ALL CUT TO THE RIGHT
Carboxy peptidase - cuts to the LEFT of any amino acid on carboxy terminal
o Always the slowest
o Competitive vs. Non-Competitive.
Competitive looks like substrate fights for active site
Vmax = Vmax
Non-competitive competing for regulatory site.
o No D in Km or affinity
· Competitive vs. Non Competitive inhibitors:
Microcytic Hypochromic anemia:
Macrophages that eat iron:
o Parasitic infection
o Impaired iron absorption
o Liver disease (live stores Fe)
Enzyme deficiencies causing inability to break up heme → Degradation problem
Symptoms: Red urine indicating hemolytic anemia.
Acute Intermittent Porphyria (most common)
Recurrent acute abdominal pain and neuropathy (remember this can be anything..headaches, ↑ ICP, etc…)
MCC = STRESS
o Can be set off by menses
MC Drugs that can cause this
o Anti – Malarial
o Hematin stop Daminolevulinic acid synthase decrease further production of porphyrin.
o Fluids to flush it out
o Sugar helps draw the excess porphyrins out
Porphyria Cutanea Tarda
-Sun blisters skin
-Starts in late childhood > 5 years old
-Early childhood < 1 years old
-Blister in the su
Myoglobin vs. Hemoglobin
Highest pO2 in umbilical vein coming from placenta (coming from mom)
o pO2 = 80
After liver pO2 to 60%
After brain pO2 to 50%
In extremities pO2 to 40%
Through Foramen Ovale and Left side pO2 = 90%
SaO2 = 90% pO2 = 60
Normal values: Hg=15, Hct=45
1g of Hg has 4 Heme sites.
Athletes pO2 between 40
→ 60 = Hypoxic period Begin anaerobic →
↑ lactic acidosis The 2nd Wind Theory An athlete must out last
this hypoxic period so that Myoglobin can begin to drop oxygen
pO2 between 40 → 60 = Hypoxic period
Begin anaerobic → ↑ lactic acidosis
The 2nd Wind Theory
An athlete must out last this hypoxic period so that Myoglobin can begin to drop oxygen
If pO2< 60, free Hg to de saturate and curve shift to Right
Hg lets go of O2 and shift to Left Hg holding on to O2
o begins in the Yolk Sac at months gestation.
o 6 months liver, spleen and flat bones → close at 1 year
o 8 months long bones
o After 1 year of age long bones are in charge of erythropoesis.
If long bones are damaged, in bone marrow > 1 year spleen will take over again = splenomegaly
Inhibitors to Hb:
Competitive inhibitor of O2
o Treatment = O2
o Non-competitive inhibitor of O2
o Km doesn’t change
o Vmax will decrease
o Treatment with O2 will not make saturation go up
Sickle Cell Disease:
Autosomal recessive, HbS
Protect Against Malaria
Amino Acid substitution: Val Glu @ position 6 of b chain
o Valine = Neutral → goes inside
o Glutamic acid = Negative (charged) → goes outside
o THIS PROVIDES THE MECHANISM FOR SICKLING
When O2 decreases, the Val on opposite sides (positions 1 and 6) attract each other and change shape
SICKLE CELL = VASOOCLUSION
o Begin to feel cold, lightheaded, and experience syncope
o Dactylitis – painful and swollen fingers and toes in new born
o Present at 4-6 months of age when Hg F switches to Hg S
o At 6 years → SPLENECTOMY
Sickle Cell Trait (SA)
Asymptomatic, but barred from extreme hypoxic situations or jobs
o Fireman, pilot, diver
Amino Acid substitution:
o Glutamic acid – (-) = outside
o BOTH STAY ON THE SURFACE = no sickling
Fe3+ can’t pick up O2 = Ferric (oxidized)
o methemaglobanemia- inborn
o MCC = 2 methemaglobanemia- drug induced (sulfa) can oxidize Fe2+/Infections d/t free radicals
o Low O2 saturation BUT pO2 will be normal
o Methylene Blue – “Give them something blue to turn them pink”
Anyl Nitrite- will convert Hg to Fe3+ not allowing CN to act.
Sodium Thiosulfate will bind CN and recant thiocyanate
Hg made up of:
o a subunit - 4 genes
o b subunit – 2 genes
# of Genes missing
% Hb Left
α – minor
(+) symptoms, basophilic stippling
α – major
β – minor
Always have ↑ HbA2 and HbF
+/- symptoms based on lifestyle
β – Major
No HbA, asymptomatic until 6 mos. b/c time when HbF → HbA; All erythropoietic organs reopen
Cooley’s Anemia (Type of β Thalassemia)
Ineffective erythropoiesis → making useless RBC
Baby making blood from everywhere:
o Frontal Bossing
o Large sternum/ clavicles
o Long tender extremities
o HCT ↑↑↑, but Hb ↓↓↓
o Total body transfusion every 60-90 days → TRANSFUSION DEPENDENT
o Recall that a RBC only lives 120 days
o 1 unit of PRBC =
Hg by 1-2g
Fe by 3-4g
Will die within I 10 years of transfusion related infections
Can die d/t Iron overload = Hemochromatosis
o Bone marrow overwhelmed with Fe due to frequent transfusions.
Infections Hep B Hep C HIV CMV EBV Hep D Malaria Bacteria Babesosis Syphuliis
Hemochromatosis: Deposit Fe into organs.
o Congenital – rare autosomal recessive, HLA3 + Chr 6
o Duodenum absorbing too much Fe leading to:
o Due to transfusions:
Bronzing accumulates in skin
o Will die of:
1st decade of life transfusion related infections
2nd decade of life HF
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