Biochem Challenging Topics - Exam 1

Non-polar AA

glycine, valine, leucine, isoleucine, phenlyalanine, proline, tryptophan, methionine, alanine

Uncharged polar AA

Serine, Threonine, Tyrosine, Asparagine, Glutamine, Cysteine

Acidic AA

Glutamate, Aspartate

Basic AA

Histidine, Lysine, Arginine

Michaelis Menten Equation

Vo=Vmax [S] / Km + [S]

Lineweaver-Burke Plot X-axis

-1/Km

Lineweaver Burke Plot Y-intercept

1/Vmax

Lineweaver-Burke Plot slope

Km/Vmax

BMP

Cl, K+, Ca2+, Na2+, Creatinine, Glucose, BUN, CO2

CMP

BMP + ALT, AST, ALK/ALP, Bilirubin, Protein, Albumin

Renal Profile

BUN, Creatinine, BUN:Creatinine, Uric Acid

Liver Profile

ALT, ASL, ALK/ALP, GGT, 5’NT, Albumin, Bilirubin, LDH

Muscle Profile

AST, LDH, CK

Cardiac Damage LDH Isoenzyme

LDH-1>LDH-2

Liver damage LDH isoenzyme

LDH-5>LDH-4

AMI CK Isoenzyme

CK-MB

Longest lasting AMI Marker

LDH-1 (and TnT)

Shortest Lasting AMI marker

myoglobin

Quickest AMI marker

Myoglobin

Slowest AMI Marker

LDH-1

Porphyria Cutanea Tarda Enzyme Deficiency

uropophyrinogen decarboxylase deficient

Porphyria Cutanea Tarda Symptoms & Onset

40-50 y/o onset d/t gradual accumulation, photosensitivity. Treated with hemin and 10% glucose injections

Acute Hepatic Porphyria Enzyme Deficiency

various enzymes

Acute Hepatic Porphyria Symptoms & Onset

onset by alcohol or drugs, varies based on what enzyme is deficient.

Erythropoietic Porphyria Enzyme Deficiency

Ferrochelatase

Erythropoietic Porphyria Symptoms & Onset

appears in childhood, photosensitivity. treated with avoidance and beta-carotene.

Causes of pre-hepatic jaundice

Sickle cell, pyruvate kinase or G6PD deficiencies

Hepatocellular Jaundice Causes

Hepatitis, liver disease

Gilbert’s Disease

minor decrease in bilirubin glucuronyltransferase (UGT1A1), unconjugated hyperbilirubinemia
Induced with stress/exercise

Crigler-Najjer I and II

severe mutation causing loss of function to bilirubin glucuronyltransferase (UGT1A1), unconjugated hyperbilirubinemia
Early onset and severe presentation
Presents as kernicterus

Kernicterus

unconjugated bilirubin exceeds albumin capacity, diffuse into basal ganglia

Dubin Johnson Syndrome

MRP2/ABCC2 transport deficiency, conjugated hyperbilirubinemia
Impaired secretion of bile into bile canaliculi & intestine"
benign condition

Rotor Syndrome

OATP1B1/OATP1B3 transport deficiency, conjugated hyperbilirubinemia
Impaired reuptake of conjugated bilirubin into hepatocytes

Prehepatic Jaundice diagnostic profile

increased LDH
increased T-BIL and I-BIL
normal LFTs

Hepatocellular Jaundice Diagnostic Profile

Increased LDH
Increased T-BIL, I-BIL, and D-BIL
Increased AST & ALT (more than ALK and GGT)

Alcohol Abuse as LFT

AST:ALT ratio >2:1

Post Hepatic Jaundice Diagnostic Profile

Increased T-BIL and D-BIL
Increased GGT and ALK
Increased 5’-NT if tested

Isolated GGT

alcohol induced biliary tree damage

Viral damage as LFT

AST & ALT > 1000

Henderson Hasselbalch Equation

pH=pKa + log [A-]/[HA]

Ka equation

=[H+][A-] / [HA]

Incompatible pH for life

<6.8 or >7.8

pKa of Bicarbonate buffer system

6.1, weakly basic to buffer addition of acids produced by metabolism

Respiratory Acidosis

low pH, pCO2 levels high
caused by hypoventilating, not breathing out enough CO2

Respiratory Alkalosis

hig pH, pCO2 levels low
caused by hyperventilation, breathing out too much CO2

Kussmaul Breathing

deep labored, hyperventilation to increase pH. In response to DKA

AA residue that binds directly to Heme

Histidine, proximal F8

AA residue that stabilizes O2

Histidine, distal E7

Negative Heterotopic Effectors for Hb

2,3-BPG, CO2, H+

Negative Heterotopic Effector Impacts on Dissociation Curve

shifts right, stabilizes T-state, decreases affinity for O2, P50 increases

Bohr Effect

Increased CO2 decreased pH, deoxyHb releases O2 to bind H+ preferentially

2,3- BPG impact on Hb

increased 2,3-BPG stabilizes T-state. Release O2 into tissues
decreased 2,3-BPG stabilizes R-state. Holds onto O2 tightly

CO impact on Hb

increased CO binds to one site and favors R form of Hb. Prevents O2 from being released into tissues, left-shift

HbF and 2,3-BPG

lower affinity for 2,3-BPG than HbA1
will bind O2 with higher affinity than HbA1 does

Rule of 3s

RBC x3 = HGB

HGB x3 = HCT

MCV Formula

HCT/RBC x 100

MCH Formula

HGB/RBC x 100

MCHC Formula

HGB/HCT x 100

Anisocytosis

size variation

Poikilocytosis

shape variation

Kidney Damage CBC Profile

normocytic, normochromic

Hb Gower 1

Hb in embryonic yolk sac

Hemoglobin C Disease

Glu6Lys, mild chronic hemolytic anemia. no specific therapy

Hemoglobin SC Disease

Compound heterozygotes of both mutations. Total Hb levels higher than HbS alone

Hemoglobin D disease

Glu121Gln, clinically significant if paired with HbS or beta-thalassemia

β-thalassemia Minor

β-thalassemia trait
one mutation of HBB gene
Adequate Hb A1 levels

β-thalassemia Major

AKA Cooley or Mediterranean anemia
two HBB mutations
impacts infants within first few months of birth
increased HbA2 levels
Skeletal changes
Life-long transfusions with concerns of iron overload

β-thalassemia Intermedia

two mutations HBB (beta+)
intermediate level of symptoms

Hb H Disease

3 defective alpha alleles, β4 tetramers. Hb H precipitates in Heinz bodies

Hemoglobin Bart Disease

4 defective alpha alleles, γ4 tetramers. Failure to make HbF resulting in fetal death

Methemoglobenemia

Fe3+ incorporated into Hb → Hb M made.
Deficiency of NADH-cytochrome b5 reductase
Chocolate cyanosis
Treated with methylene blue