Flashcards in Biochem Deck (104):
Glycogen storage diseases
(Very Poor Carbohydrate Metabolism)
Von Gierke (type I)
Pompe (type II)
Cori disease (type III)
McArdle disease (type V)
What is it? Other findings?
Severe fasting hypoglycemia
Increased glycogen in liver
Von Gierke Disease
(Increased blood lactate, increased TGs, increased uric acid, hepatomegaly, enlarged kidneys)
Glucose 6 Phosphatase is deficient
Von Gierke Disease
(can't make glucose 6 phosphate into glucose)
Treatment of Von Gierke Disease
Glucose 6 Phosphatase deficiency treated with frequent oral glucose/cornstarch and avoidance of fructose and galactose
Deficiency of Pompe disease
Lysosomal a-1,4-glucosidase (acid maltase) (degrades glyocogen in lysosomes)
Cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, diaphragm weakness
What is the inheritance of glycogen storage diseases (Very Poor Carbohydrate Metabolism)?
Milder form of Von Gierke disease with normal blood lactate levels
Cori disease (debranching enzyme a-1-6-glucosidase)
Increased glycogen in muscle but it cannot break down
Findings in McArdle disease
Painful muscle cramps, myoglobinuria (red urine) with strenuous exercise and arrhythmia from electrolyte abnormalities
Enzyme deficiency in McArdle disease
Skeletal muscle glycogen phosphorylase (myophosphorylase) (liberates glucose 1 phosphate residues)
Other findings of Cori cycle
Hypoglycemia, hyperTG, ketoacidosis, hepatomegaly, ACCUMULATION of SHORT DEXTRIN like structures in cytosol of hepatocytes, no fatty infiltration of liver
NORMAL kidneys, lactate and uric acid
Accumulation of short dextrin like structures in cytosol of hepatocytes
Which body tissues are deficient in sorbitol dehydrogenase?
Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease, corneal opacities, pain, HTN
Fabry disease (lysosomal storage disease)
X linked Recessive
Deficiency in Fabry disease
Alpha-galactosidase A is deficient
Ceramide trihexoside accumulates
Most common lysosomal storage disorder
Gaucher disease (glucocerebrosidase; B-glucosidase deficiency)
Lipid laden macrophages resembling crumpled tissue paper
Gaucher cells seen in Gaucher disease (lysosomal storage disorder)
Lysosomal storage disorder with severe bone pain
Gaucher disease - aseptic necrosis of femur, bone crises, osteoporosis
X linked recessive lysosomal storage disorder
Fabry disease - alpha galactosidase A deficiency
Progressive neurodegeneration, HEPATOSPLENOMEGALY, foam cells, CHERRY RED spot on macula
Foam cells are lipid laden macrophages
Niemann Pick Disease
Progressive neurodegeneration, developmental delay, CHERRY RED spot on macula, lysosomes with ONION skin, NO hepatosplenomegaly
Tay Sachs disease (deficiency in hexosaminidase A)
What accumulates in Tay Sachs?
Sphingolipidoses with optic atrophy
Krabbe disease (Galactocerebrosidase deficiency)
Metachromatic leukodystrophy deficiency
CENTRAL and peripheral demyelination with ataxia, dementia
Metachromatic leukodystrophy (arylsulfatase A deficiency)
Developmental delay, gargoylism, airway obstruction, corneal clouding (vision loss), hepatosplenomegaly
Hurler syndrome - alpha-L-iduronidase deficiency
Mild Hurler + aggressive behavior; NO corneal clouding
Hunter syndrome (iduronate sulfatase deficiency)
Inheritance of Hurler and Hunter syndrome
Hurler - Autosomal recessive
Hunter - X linked recessive
How do you differentiate between Cori disease and Von Gierke disease?
Von Gierke - has enlarged kidneys, with increased lactate and uric acid
Cori disease - normal kidneys, lactate and uric acid
Both have hypoglycemia, increased TGs, hepatomegaly
No man picks his nose with his sphinger
Niemann-Pick - sphingomyelinase deficiency
Tay Sach deficiency
Hunter vs. Hurler
Hunter's see clearly (NO corneal clouding)
Hunter's is X linked recessive
When is non-homologous end joining mutated?
(Non-homologous end joining brings together 2 ends of DNA fragments to repair ds breaks)
Direction of DNA and RNA synthesis?
Direction of protein synthesis?
Both DNA and RNA are synthesized 5' to 3'; mRNA is read 5' to 3'
Protein synthesis is N terminus to C terminus
Drugs blocking DNA replication have modified what? Why?
Modified 3' OH preventing addition of the next nucleotide because the triphosphate bond is the target of the 3' hydroxyl attack - the 5' end of the incoming nucleotide bears the triphosphate (energy source for bond)
What is fMet? What does it stimulate?
fMet is N-formylmethioine; this is what AUG start codon codes for in prokaryotes
fMet stimulates neutrophil chemotaxis
Effects of alpha amanitin
Inhibits RNA polymerase II (responsible for making mRNA) and causes severe hepatotoxicity
(Found in death cap mushrooms)
Where does RNA processing occur?
hnRNA becomes mRNA via capping, polyadenylation and splicing in the NUCLEUS
mRNA quality control occurs at P-bodies in the CYTOPLASM (contains exonuclease, decapping enzymes, microRNAs; they can be stored here for future translation)
Anti-spliceosomal snRNPs (anti-Smith Antibodies)
Highly specific for SLE
Which amino acids are required during periods of growth?
Arginine and Histidine
Essential amino acids (PVT TIM HaLL)
Reduced renal tubular reabsorption of tryptophan
Hartnup disease --> causes pellagra symptoms (dermatitis, dementia, diarrhea)
Symptoms of Methemoglobinemia
headache, dizziness, nausea, shortness of breath, confusion, seizures, and coma
-Blood may have a characteristic muddy color secondary to the oxidization state of iron
Clinical hallmarks of NF 1
Cafe au lait spots
Lisch nodules (pigmented iris hamartomas)
Skeletal abnormalities are common - scoliosis or vertebral defects or long bone dysplasia
Which types of cells are most affected by chemotherapy?
Labile tissues that never got to G0 and divide rapidly with a short G1 phase --> bone marrow, gut epithelium, skin, hair follicles, germ cells
How does golgi apparatus modify asparagine, serine and threonine?
Modifies N-oligosaccharides on asparagine
Modifies O oligosaccharides on serine/threonine
What is I-cell disease?
Failure of Golgi to phosphorylate mannose residues (decreased mannose-6-phosphate) on glycoproteins so that proteins get secreted extracellularly instead of going to the lysosomes
Defect in N-acetylglucosaminyl-1-phsophotransferase
Coarse facial features, clouded corneas, restricted joint movement
Coarse facial features, clouded corneas, restricted joint movement
I-cell disease (fatal in childhood) - Golgi can't phosphorylate mannose residues on glycoproteins = defective trafficking to lysosomes
Function and examples of each:
b. Intermediate filaments
a. Muscle contraction, cytokinesis; actin
b. Maintain cell structure; vimentin, design, cytokeratin, lamina, GFAP, neurofilaments
c. Movement, cell division; cilia, flagella, mitotic spindle, axonal trafficking, centrioles
Which molecular motor proteins are responsible for which transport?
Dynein - retrograde to microtubule (+ --> - )
Kinesin - anterograde to microtubule ( - --> + )
Structure of cilia
9 + 2 arrangement of microtubule doublets
Coordinated contraction via gap junctions
Axonemal dynein - ATPase that links peripheral 9 doublets and causes bending of cilium by sliding of doublets
What is Menkes disease?
X linked recessive CT disease caused by impaired copper absorption and transport --> decreased activity of lysol oxidase (copper is necessary cofactor) --> brittle, kinky hair, growth retardation, hypotonia
What is responsible for cross linking step of collagen?
Tropocollagen molecules are cross linked by copper containing lysyl oxidase
Characteristics of osteogenesis imperfecta
Blue sclera - from translucency of CT over choroidal veins
Dental imperfections due to lack of dentin
Types of Ehlers-Danlos and collagen type they affect
Classical type (joint and skin) --> mutation in type V collagen
Vascular type (vascular, organ rupture) --> deficient type III collagen
Where is elastin located?
Skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava
Difference between glycine, proline and lysine residues in Collagen and Elastin
Collagen - hydroxylated
Elastin - NONhydroxylated
What gives elastin it's elastic properties?
Cross linking between 4 different lysine residues
Quad screen in Down syndrome
Decreased alpha fetoprotein
Increased inhibin A
Quad screen in Edwards (trisomy 18)
Decreased alpha fetoprotein
DECREASED or normal inhibin A
Quad screen in Patau syndrome (13)
Quad screen not helpful
Decreased free bhCG
Increased nuchal translucency
Chromosome 15 disorders
Prader willi, Angelman
Chromsome 13 disorders
Patau syndrome, Wilson disease
Chromosome 11 disorders
Chromosome 9 disorders
Chromosome 7 disorders
Williams syndrome, CF
Chromosome 5 disorders
Cri-du-chat syndrome, Familial adenomatous polyposis
Chromosome 4 disorders
ADPKD with PKD2 defect,t Huntingtons
Chromosome 3 disorders
Von Hippel Lindau disease, Renal cell carcinoma
Chromosome 16 disorders
ADPKD with PKD1 defect
What is Cri du chat syndrome?
Congenital micro deletion of short arm of chromosome 5
Microcephaly, moderate to severe ID, high pitched mewing, epitcanthal folds, cardiac abnormalities
What is Williams syndrome?
Congenital micro deletion of short arm of chromosome 7; distinctive elfin facies, ID, hypercalcemia (from increased sensitivity to vitamin D), well developed verbal skills, extreme friendliness with strangers, cardiovascular problems
Which metabolic pathways occur in BOTH cytoplasm and mitochondria? (HUGs take 2)
Where do these pathways take place?
a. Fatty acid oxidation
c. Fatty acid synthesis
d. Acetyl coA production
e. HMP shunt
f. Protein synthesis
g. TCA cycle
h. Oxidative phosphorylation
j. Steroid synthesis
k. Cholesterol synthesis
a. fatty acid oxidation - mitochondria
b. glycolysis - cytoplasm
c. fatty acid synthesis - cytoplasm
d. acetyl coA production - mitochondria
e. HMP shunt - cytoplasm
f. protein synthesis - cytoplasm (RER)
g. TCA cycle - mitochondria
h. oxidative phosphorylation - mitochondria
i. ketogenesis - mitochondria
j. steroid synthesis - cytoplasm (SER)
k. cholesterol synthesis - cytoplasm
a. Rate determining enzyme of Glycolysis
a. Phosphofructokinase 1 (PFK1)
b. Stimulated by AMP, fructose 2,6 bisphosphate; inhibited by ATP, citrate
a. Rate determining enzyme of Gluconeogenesis
a. Fructose 1,6 bisphosphatase
b. Stimulated by ATP, acetyl coA; inhibited by AMP, fructose 2,6 bisphosphate
a. Rate determining enzyme of TCA cycle
a. Isocitrate dehydrogenase
b. Stimulated by ADP, inhibited by ADP, NADH
a. Rate determining enzyme of Glycogenesis
a. Glycogen synthase
b. Stimulated by glucose-6-phosphate, insulin and cortisol; inhibited by epinephrine, glucagon
a. Rate determining enzyme of Glycogenolysis
a. Glycogen phosphorylase
b. Stimulated by glucagon, epinephrine, AMP; inhibited by insulin, glucose-6-phosphate, ATP
a. Rate determining enzyme of HMP shunt
a. Glucose 6 Phosphate Dehydrogenase
b. Stimulated by NADP+; inhibited by NADPH-
a. Rate determining enzyme of De novo pyrimidine synthesis
a. Carbamoyl Phosphate Synthetase II
b. Stimulated by ATP, inhibited by UTP
a. Rate determining enzyme of de novo purine synthesis
a. Glutamine-Phosphoribosylpyrophosphate (PRPP) amidotransferase
b. Inhibited by AMP, IMP and GMP
a. Rate determining enzyme of urea cycle
a. Carbamoyl Phosphate Synthetase I
b. Stimulated by N-acetylglutamate
a. Rate determining enzyme of fatty acid synthesis
a. Acetyl coA carboxylase
b. Stimulated by insulin, citrate; inhibited by glucagon, palmitoyl coA
a. Rate determining enzyme of fatty acid oxidation
a. Carnitine acyltransferaes I
b. Inhibited by malonyl coA
a. Rate determining enzyme of Ketogenesis
HMG Co A synthase
a. Rate determining enzyme of Cholesterol synthesis
a. HMG Co A reductase
b. Stimulated by insulin, thyroxine; inhibited by glucagon, cholesterol
How many ATP are produced per glucose via:
a. Malate-aspartate shuttle
b. glycerol-3-phosphate shuttle
c. anaerobic glycolysis
d. glycolysis with arsenic
a. 32 ATP
b. 30 ATP
c. 2 ATP
d. 0 ATP
Universal electron acceptors:
a. What is NAD+ used for?
b. What is NADPH used for?
a. catabolic processes to carry reducing equivalents away as NADH
b. anabolic processes as supply of reducing equivalents
a. NAD+ is generally used in which processes?
b. NADPD is used in which processes?
c. What reactions is NADPH used in?
a. Catabolic - carries reducing equivalents away as NADH
b. Anabolic - steroid and fatty acid synthesis as a supply of reducing equivalents
c. Anabolic processes, Respiratory burst, Cytochrome P450 system, Glutathione reductase
What is carried on the following molecules?
b. NADH, NADPH, FADH2
c. CoA, lipoamide
a. Phosphoric groups
c. Acyl groups
e. 1 carbon units
f. CH3 groups
How does arsenic affect ATP production?
It causes glycolysis to produce zero net ATP
It inhibits lipoic acid which is a co-factor needed for pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase --> vomiting, rice water stools, garlic breath
Vomiting, rice water stools, garlic breath
Arsenic poisoning --> inhibits lipoic acid (needed for pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase)
Neurologic defects, Lactic acidosis, Increased serum alanine
Pyruvate dehydrogenase deficiency (can't make pyruvate into acetyl co-A --> gets shunted to lactate or alanine)
Treatment for pyruvate dehydrogenase deficiency
Increased intake of ketogenic nutrients (lysine and leucine)
Which co-factors are needed for the following enzymes?
a. Alanine aminotransferase (pyruvate --> alanine)
b. Pyruvate Carboxylase (pyruvate --> oxaloacetate)
c. Pyruvate dehydrogenase (pyruvate --> acetyl coA)
d. Lactate dehydrogenase (pyruvate --> lactate)
b. Biotin - B7
c. B1, B2, B3, B5, Lipoid acid
What does the TCA cycle produce?
that all = 10 ATP/acetyl coA
How can odd chain fatty acids produce glucose?
They yield propionyl coA during metabolism which can enter the TCA cycle as succinyl coA and undergo gluconeogenesis
(Even chain fatty acids can't do this because they only produce acetyl coA equivalents)
Where does HMP shunt take place and in which tissues?
In the cytosol - no ATP needed or produced
In the lactating mammary glands, liver, adrenal cortex, and RBCs - sites of fatty acid or steroid synthesis
Failure to track objects or develop social smile
Galactitol accumulates (galactose --> galactitol by aldose reductase)