Clinical Biochemistry Flashcards
(44 cards)
Lead Poisoning
Typically children who ingest paint, adults (factory worker, bullets)
Decreased heme synthesis and increased RBC protoporyphryin
Affected Enzyme: Ferrochelatase and ALA dehydratase
Accumulated Substrate: Protoporphyrin, D-ALA in blood
Symptoms: microcytic (sideroblastic) anemia, GI (colicky abdominal pain, lead lines on gums/metaphyses) and Kidney disease
Adults: headache, memory loss, demylination (wrist/foot drops)
Children: mental deterioration
Increase in pyridoxal phosphate during poisoning
Labs: basophilic stippling (inhibition of rRNA degradation)
increased iron, normal/decreased TIBC, increased ferritin
Treatment: dimercaprol and EDTA
Succimer for children
Acute intermittent porphyria
AD
Affected enzyme: porphobilogen deaminase (uroporphobionogen III synthase)
Accumulated substrate: Porphobilogen, D-ALA
(coporphobilinogen in urine)
Symptoms: painful abdomen, port wine colored urine (darkens on exposure to light), polyneuropathy, psychological disturbances (anxiety)
Precipitated by drugs that induce CYP450 (phenytoin, griseofulvin, phenoarbital)-due to CYP450 needing heme, increase in ALA synthase cannot be matched by deficient enzyme), alcohol and starvation
Treatment: glucose, heme which inhibit ALA synthase
Porphyria cutanea tarda
Most common
Affected enzyme: Uroporphyrinogen decarboxylase
Accumulated substrate: Uroporphyrin (tea color urine)
Symptoms: blistering when exposed to sun exposure (due to porphyrin mediated superoxide free radical formation)
Edema, pruiritis, pain and erythema
Pyruvate carboxylase
Irreversible enzyme of gluconeogenesis
Pyruvate to oxaloacetate
Happens in mitochondria
Requires biotin, ATP, activated by acetyl CoA
Phosphoenolpyruvate
Irreversible enzyme of gluconeogenesis
In cytosol
Oxaloacetate to phospenopyruvate
Requires GTP
Fructose 1,6 bisphosphatase
Irrevesrible enzyme of gluconeogenesis
In cytosol
Fructose 1,6 BP to fructose 6-P
Glucose 6 phosphatase
Irreversible enzyme of gluconeogenesis
Happens in ER
Glucose 6-P to glucose
Isocitrate dehydrogenase
Irreversible part of TCA
Isocitrate to a keto glutarate
Produces NADH and CO2
Inhibited by ATP and NADh
Activated by ADP
a ketocgulatarate
Irreversible part of TCA
Produces NADH and CO2
Inhibited by Succinyl CoA, NADH and ATP
Succinyl CoA to Succinate
Produces GTP and CoA in TCA
Succinate to Fumarate
Produces FADH2
Malate to NADH
Pruduces NADH
TCA yields
3 NADH 1 FADH2 2CO2 1 GTP per acetyl CoA Add up to 10 ATP per acetyl CoA x2 for glucose
Glucokinase/hexokinase
Uses ATP
Glucose to glucose 6 phosphate
Hexokinase Inhibited by glucose 6 P
Glucokinase inhibited by fructose 6P (liver and B cells)
Both inhibited by ATP, Citrate
Accelerated by AMP and Fructsoe 2,6 BP
ATP producing steps of glycolysis
1,3 Bisphosphgylcerate to 3 Phosphoglycerate using phosphoglycerate kinase
Phosphoenolpyrugate to pyruvate using pyruvate kinase
Inhibited byt ATP, alanine, cAMP
Activated by fructose 1,6 bisphosphate
Fructose 2, 6 bisphosphate and fasting/fed state
Fasting state: increaesd glucagon, increased cAMP Increased PKA Increased FBPase-2 increasing fructoese 6 phosphate leading to glucogneeogenesis
Fed state: increased insulin, decreased cAMP, decreased PKA, decrease FBPase 2, increased PFK leading into more glycolysis
Pyruvate dehydrogenase activation
increased NAD/NADH ration
increased ADP
Increased Ca2+
Happens in the mitochondria
Fatty acid oxidation
Acetyl CoA production
TCA cycle
Oxidative phosphorylation
Happens in Cytoplasm
Glycolysis Fatty acid synthesis HMP shunt Protein synthesis (RER) Steroid synthesis (SER) Cholesterol synthesis
Kwashiorkor
Protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty change due to decreased apolipoprotein synthesis), anemia
Small child with swollen belly
Marasmus
Total calorie malnutrition resulting in tissue and muscle wasting , loss of subcutaneous fat, and variable edema
Robertsonian Translocation
Nonreciprocal chromosomal translocation that involves chromsomes 13, 14, 14, 21 and 22
Long arms of acrocentric (centromeres near the ends) fuse at the centromere and the 2 short arms are lost
Balanced translocations normally do not cause any abnormal phenotype
Unbalanced causes miscarriage, stillbirth, and chromosomal imbalance
Williams Syndrome
Congenital microdeletion of long arm of chromosome 7 (deleted region includes elastin gene)
Findings: elfin facies, intellectual disability, hypercalcemia well developed verbal skills, extreme friendliness, cardiovascular problems
22q11 deletion syndromes
Variable presentation
Cleft palate,, abnromal facies, thymic aplasia (T Cell deficiency), cardiac defects, hypocalcemia,
Aberrant development of 3rd and 4th brachial pouches