Biochemistry Flashcards
(26 cards)
HMP SHUNT AND GLUTATHIONE- rbc
RBC need energy from glycolysis and NADPH to prevent oxidative damage
- 1 NADPH is generated from oxidative portion of HMP shunt where g-6-p is converted to 6 phosphogluconolactone/pgl. Hydrolysis of this molecule to ribulose 5 phosphate via 6pgl dehydrogenase makes another NADPH
- Hydrogen peroxide is formed from partial oxygen destrogen and glutathione perioxidase is needed to convert that to water
Where the HMP shunt/NADPH comes in
NADPH+H helps regenerate reduced glutathione (made by glutathione reductase) which is needed for glutathione peroxidase to convert hydrogen peroxide to water.
Fatty acid oxidation
Fatty acid in cytoplasm to acylcoA using acyl coA synthase. Cat1 and carnithine covert acyl coA to acyl Carnithine which crosses the inner mitochondrial membrane and catII converts back to Carnithine and acyl coA. Deficient in Carnithine leads to weakness post exercise, increased muscle triglyceride, low ketone and low myoglobin
Next, first step in beta oxidation
acyl coA needs fadh2 and acyl coA dehydrogenase …series of subsequent steps to acetyl coA which can enter TCA, or if this is overwhelmed, is converted to ketones. Deficiency here leads to low ketones and low glucose.
TATA and CAAT boxes
TATA is 25bp above coding site and CAAT is 60 to 80. It is to one of these that RNA polymerase attaches. In eukaryotes, other factors needed to aid RNA polymerase II recognition of the box
Collagen Synthesis
- Procollagen is exocytosed by fibroblasts or SMC
- It becomes insoluble Tropocollagen when it its terminal regions are exocytosed
- it is tropocollagen that aggregates ton form collagen fibrils (Lysyl oxidase converts NH2 terminus of lysine residues to aldehyde in collagen fibers to strengthen collagen fibers)
Before this:- prolyl 4hydroxylase hydroxylates prolione on procollagen chain which forms the stable triple helix
Water soluble vitamins
-Vitamin B deficiency
All the b’s and C’s. The B’s do not include 4, 8 (10,11)
-dermatitis, glossitis and diarrhea
Names of the B’s
-important note
1 Thiamine (TPP) 2 Riboflavin (FAD, FMN) 3 Niacin (NAD+) 5 pantothenic acid or coA 6 Pyridoxine (PLP) 7 Biotin 9 Folate 12 Cobalamin They all wash out except for 7 and 9 which are stored in the liver!
fat soluble vits
- Name them, important note?
- What organ is responsible for absorbing them
- What causes their deficiency
A,D,E,K
- need terminal ileum and pancreas
- toxicity is more common as they fat accumulate
- sprue, malabsorption (steartorrhea),cystic fibrosis, mineral oil intake
22q11 deletion
- Syndromes
- Mnemonic
CATCH 22 (Cleft, Abnormal face, Thymic aplasia and T cell deficiency, Cardiac defect and Hypocalcemia secondary to Parathyroid aplasia)
-Velocardiofacial:- Cardiac, Cleft, Facial
-DiGeorge:- Cardiac, Thymus hypoplasia, Parathyroid
The 3rd and 4th branchial pouches dont form
In this syndrome, people are overly friendly with strangers, faces look like elves, some intellectual disability but welldeveloped verbal skills
- What endocrine abnormality seen
- Other structural abnormalities here?
Williams Disease
- Hypercalcemia due to vitamin D increased sensitivity
- Cardiovascular issues
Robertsonian seen where
-Describe it
Seen in Downs and Pataus
-basically 13.14.15,21 and 22 which have short p near centromere (acrocentric), translocates and short arms are lost!
If balanced, OK
If unbalanced problem!
Mnemonic for autosomal trisomies
Drinking age:- Downs 21
Election age:- Edwards 18
Puberty age:- Patau 13
Downs Syndrome- features and consequences
common genetic defects
-flat face
-intellectual disability (#1 genetic cause)
-single palmar crease
-space between toe 1 and 2
-epicanthal folds
-brushfield spot (white grey on periphery of iris, aggregates of connective tissue)
-duodenal atresia
-Hirschsprung
-ASD (ostium primum type)
Consequence
-ALL and AML
-Alzheimers (>35yr)
-4% Robertsonian
-1% mosaicism (not associated with mum, mitotic error)
-95% meiotic non disjunction
-Usually due to >45 year old mother
Quad screen?
Downs, Edwards, patau 1
=1st trimester
=2nd trimester quad
- free HcG
- a-fetoprotein
- estriol
- inhibin A
- 2nd trimester
D:- afp and estriol down, hcg and inhibin A up
(first trimester shows decreased PAPP, INCREASED HcG, nuchal translucency and hypoplastic nasal bone)
E:-all are down, inhibinA can be normal
(1st trimester shows decreased PAPP and hcG)
P:- no quad, but first trimester can show decreased PAPP-A and hcG with increased nuchal translucency
Edward features
ROCKER BOTTOM FEET Small jaw (micrognathia) low set Ears clenched hands Severe intellectual disability Congenital heart disease Prominent occiput DEATH WITHIN 1 YEAR
Patau features
cleft LIP/PALATE/ holoProsencephaly/ Polydactyly
- congential heart disease
- rocker bottom feet
- microcephaly+micropthalmia
- severe intellectual disability
- death within 1 year
Tri nucleotide expansion disease mnemonic
- name them
- trinucleotides (mnemonic)
-Try hunting for my fried eggs
-All EXCEPT Friedreich start with C and end with G
Huntington (CAG), MyoTonic dystrophy (CTG), Friedreichs (GAA), FraGile X (CGG)
-Or X Girlfried
-First Aid
-Helped Ace
-My Test
Fragile X -inheritance pattern -gene affected -features Myotonic type 1 dystrophy traits -inheritance pattern -gene affected -features
Fragile X:-
- X linked
- methylation and expresson of FMR1 gene
- 2nd leading genetic cause of severe intellectual disability with MVP, xtra large face, jaw, testes and ears. Autism
Muscular dystrophy
- X linked
- Expansion of DMPK gene
- Myotonin protein kinase overexpressed
- Myotonia, muscle wastes, frontal balding, cataracts, atrophied testicle, arrhythmia
Most common cause of death in muscular dystrophies
- which one is worse
- inheritence pattern
- role of deletions
- main features
Dilated cardiomyopathy!!!
- Duchenne worse than Becker
- Becker onset in adolescence or adults. Duchenne <5 y onset
- X link FRAMESHIFT mutation that affects dystrophin DMD (longest codiing region ) gene
- DELETIONS CAN CAUSE BOTH
- pseudohytrophied (fibrofat replacement) calf muscle
- Weakness in pelvic girdle first (Gower maneuver)
Role of DMD gene
-diagnosis of dystrophy
- Anchors muscle fibers (cardiac and skeletal mostly)
- Connects actin to transmembrane a and b dystroglycan that are connected to ECM
- Loss leads to myonecrosis
Diagnosis
Increased CPK and aldolase
Confirm with Western Blot and Muscle biopsy
Mnemonic for X linked Recessive Disorders
Word to women
Be Wise Fools GOLD Heeds Silly HOpe Brutons Wiskott-Aldrich Fabry G6PD Ocula-albinism Lesch-Nyhan Duchenne (becker too( Hunter Syndrome Hemophilia A/B Ornithine transcarbamylase deficiency -male always affected -females affected depending on percentage X inactivation of the chromosome with mutant/normal gene
four NOs of Hardy Weinberg
NO
- migration
- mutation at locus
- no assigned mating (RANDOM)
- natural selection
CFTR gene chromosome
- most common cause
- pathophysiology
- treatment
Chromosome SEVEN
- deletion Phe508
- ATP Cl channel (secretes in lung and GI, absorb in sweat). Misfolded protein, retained in RER
Cystic Fibrosis Diagnosis, Complications, Treatment
->60meq/L salt in sweat
Contraction alkalosis with hypokalemia (similar to loop diuretic use)
-Malabsorption, Steatorrhea, ADEK insuffiency, infertile males (no vas deferens/sperm), pancreatic insufficiency, Pseudomonas (reticunodular CXR), chronic bronchitis/bronchiectasis, nasal polyps and meconium ileus infants
-Treat with Nacetylcysteine (loosen disulfide bond in mucus glycoprotein), dornase alfa (DNase) to clear leukocyte debris
Autosomal recessives
- Albinism and ARPKD
- CF
- Glycogen storage
- Hemochromatosis
- Kartagener
- Mucopolysaccharidoses (X HUNTERS)
- PKU
- Sickle Cell, -Sphingolipidoses except Fabrys
- Thalessemias
- Wilsons
