COPI trafficking?

COPII trafficking?

COPI - retrograde (Golgi→ER)

COPII - anterograde (RER→cis-Golgi)

Intermediate Filaments and where they stain

(stains key for marking tumors):

• Vimentin - CT (sarcomas, some carcinomas)
• Desmin - muscle (rhabdomyosarcoma, leiomyosarcoma)
• Cytokeratin - epithelial cells (carcinomas mainly)
• GFAP - neuroglia (ex: astrocytoma, ependymoma)
  
• Neurofilament - neurons (adrenal neuroblastoma, PNETs)

deletion of normally active maternal allele (imprinting)

-on ch 15

Si/Sx: metnal retardation, siezures, ataxia, inappropriate laughter ("happy puppet")

Mitochondrial Inheritance

degeneration of retinal ganglion cells and axons → acute loss of central vision

Bruton's agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry's dz, G6PD def., Ocular Albinism, Lesch-Nyhan syndrome, Duchenne's muscular dystrophy, Hunter's syndrome, Hemophilia A & B

"Be Wise, Fool's GOLD Heeds Hope"

*assoc. Becker's muscular dystrophy w/ Duchenne's too

*Chronic Granulomatous dz is X-linked recessive in ~70% of cases

Edward's (trisomy 18)

vs.

Patau's (trisomy 13)

Both: severe mental retardation, rocker-bottom feet, ocngenital heart dz, death w/i 1 yr of birth

• Edwards: micrognathia, clenched hands, low-set ears, prominent occiput

• Patau's: cleft lip/palate, holoprosencephaly, polydactyly, microcephaly, microphthalmia

TPP is cofactor for what 4 enzymes?

(Thiamine/Vit B1 → TPP)

1. Pyruvate dehydrogenase (glycolysis)
2. α-ketoglutarate dehydrogenase (TCA cycle)
3. Transketolase (HMP shunt)
4. Branched-chain AA dehydrogenase

Carboxylation enzymes (addition of a 1-carbon group):

1. Pyruvate carboxylase (pyruvate → oxaloacetate)
2. Acetyl-CoA carboxylase (Acetyl-CoA → malonyl-CoA)
3. Propionyl-CoA carboxylase (propionyl-CoA → methylmalonyl-CoA)
   

• Fatty acid oxidation (β-oxidation)
• acetyl-CoA production
• TCA cycle
• oxidative phosphorylation
• ketone synthesis
• CPS I and ornithine transcarbamoylase (OTC) of urea cycle
  

• glycolysis
• fatty acid synthesis
• HMP shunt
• protein syn (RER)
• steroid syn (SER)

Lysine and Leucine

Used to Tx Pyruvate Dehydrogenase def. 

(diet of high fat content also used in Tx of PDH def.)

2,4-DNP

aspirin (fevers occur after aspirin OD)

thermogenin (aka UCP1, in brown fat)

ATPase inhibitor

Electron Transport Inhibitors

(by complex)

• I - amytal, rotenone, MPP
• III - antimycin A
• IV - H₂S, CO, CN^-, Azide (N₃^-) - "4 -ides for IV"
  

Si/Sx of Ammonia intox.

Tx of hyperammonemia

Si/Sx: tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Tx:

if due to liver dz = lactulose

if due to urea cycle enzyme deficiencies = benzoate or phenylbutyrate

phenylalanine→tyrosine→Dopa→Dopamine→NE→Epi

*tyrosine→thyroxine

*Dopa→melanin

tryptophan→ niacin (→NAD/NADP)

*requires B6

tryptophan → serotonin (→melatonin)

*requires BH4

histidine → histamine

*requires B6

glycine → porphyrin (→heme)

*requires B6

creatine

urea

nitric oxide (NO)

glutmate → GABA

*via glutamate decarboxylase - requires B6

glutamate → glutathione

*no B6 → no GABA → seizures/convulsion

Catecholamine Synthesis

(main 3 enzymes)

1. phenylalanine → tyrosine     (phenylalanine hydroxylase)
2. tyrosine → dopa     (tyrosine hydroxylase - rate limiting)
3. dopa → dopamine     (dopa decarboxylase - *requires B6; inhibited by carbidopa)

hypoketotic hypoglycemia, weakness, and hypotonia

-due to inability to transport LCFAs into mitochondria → toxic accumulation

*sidenote: Malonyl-CoA inhibits the carnitine shuttle

Fructose

*b/c can bypass rate limiting PFK-1

(via fructokinase to F-1-P and then via aldolase B to DHAP and G3P)

*glucose, mannose, and galactose all must all be metabolized by PFK-1