BCHM Diseases/Drugs

• -prion infections agent
• -scrapie (sheep.cow), madcow, kuru
• -known as "spingiform encephalopathies"
• -normally prions exist in brain with alpha helices and no beta sheets, but presence of beta sheets cause the disease

• adds an additional splicing site --> frame shift mutation
• reduces synthesis of beta-hemoglobic chain and results in anemia

• mild form
• causes decreased synthesis of type I collagen
• prone to fractures, blue sclera, & hearing loss
• blue sclera- results from extremely thin collagen in eye so you can see membrane beneath

• severe form
• no synthesis of Type I collagen whatsoever
• glycine replaced by bulky side chain and prevents collagen triple helix from forming
• lots of bone fracture compared to type I

• defect in fibrillin1 which changes the mechanical properties of ECM
• excessive Growth Factor B, which is normally regulated by fibrillin

caused by low levels of LDOPA

• Vitamin C (abscorbic acid) deficiency
• cause: hydroxylation of proline.lysine prevented so interchain H-bonding is reduced
• symptoms: subcutaneous extravascation due to capillary fragility

• mutation it Type V Collagen
• hyperextensive joints
• stretchy skin

• Upper respiratory tract infection
• dangerous rxn: EF2 + ADP-ribose (added by diptheria) ---> transloaction
• protein synthesis is inhibited
• mebranous pharyngitis (pseudo-membrane)
• treatment: nicotinomide

• prevents mRNA splicing b/c antibodies itnerfere with U1 component of splicesome
• rash,fever,arthritis,fatique, kidney problems
• lU₁pus

• irreversible inhbitor
• (nerve gas)
• binds to OH group of serine
• nonspecific

• acyl transferase inhibited from converting lysosomal CardioLipin to regular CL so lysosomal CL builds up causing cardiohypertrophy
• *note- CL also known as diphosphatidylglycerol

• caused by sphignomyelin accucmulation in lysosomes due to defective sphignomyelinase
• lipid lysosomal disease , so cant break down fats/cholesterol

• thick mucus buildup in respiratory tract and pancreatic duct
• due to absense of Cl- secretions due to ABC transporter issue and cystic fibrosis transmembrane conductase regulator (CFTR)
• affects digestion of proteins and lipids in SI (but carbs are fine)
• mucus dries up and blocks ducts/airways
• high NaCl levels found in sweat
• treated with short-medium chain FA diet and excess protein

Cystic Fibrosis, Zellweger Syndrom, Tangier Disease, Adrenoleukodsytrophy, Sisterolemia (failure to pump plant sterol back into lumen)

Due to release of cAMP and Ca2+ which activates PK-A and releases water (diarrhea)

Mutation in 12s rRNA Streptomycin and gentamysinbinds to 12s rRNANo translation of ATPsynthase

• "Lactic Leucy"
• Mutation in tRNA leucine
• 5-15 yo age onse tStroke
• Lactic acid - vomiting,tiredness, muscle weakness

• "Lys(ine)e those red fibers"
• Mutation in tRNA for lysine(encoded by mt
• )Late childhood -->adulthood
• Myoclonus- uncontrollablemuscle jerking
• Seizures, lactic acidosis,dementia, cardiac problems
• Ragged red fibers = clumbs of enlarged mito

• Mutation in complex I
• Optical nerve damage - lossof bilateral vision
• passed onto all offspring

• reoxidizes reduced disulfide bonds making pyruvate and lactate so stable that they begin to build up --> acidosis and decrease in E
• acts on enzymes containing lipoic acid (ex: PDH, glyceraldehyde 3 phosphate dehydrogenase)
• treatment: 2,3 mercappropanol (competes with lipoic acid)

• Deficiency in thiamine (Vitamin B12) results in PDH complex E1 not being able to decarboxylate pyruvate because the TPP is missing
• Severe forms: Beri Beri and Wernicke Korsakoff Syndrome

• Type of Thiamine Deficiency
• Asia- eating polished rise with the husk removed (source of thiamine)
• Wet & dry forms depending on presence of edema
• neuromuscular cardiovascular disorders, delirium, memory loss, muscle weakning, increased venous return, peripheral vasodilation, opthalomogplegia
• death by high output cardiac failure

• Thiamine Deficiency
• common in chronic alcoholics and malnutrition

Weirnike's enscephalopathy (acute) - delerium, mental ataxia, opthalmoplegia

Korsakoff psychosis (chronic)- anterograde amnesia, distinct pattern of brain damage, IRREVERSIBLE!!

Treatment- thiamine injections before chronic phase

• Defect of PDH E1 complex
• inability to convert pyruvate to acetyl coA
• X linked dominant
• increased levels of pyruvate, lactate, alanine, alphaketo glutarate
• causes congenital lactic acidosis
• treatment: low carb diet

• name: Von Gierke's Disease
• enzyme defect: G6Pase

• affects intestinal mucosa, liver, kidneys
• most common type
• cannot dephosphorylate
• hypoglycemia, hepatomegaly, lactic acidemia, hyperlipidemia

treatment: avoid fasting, eat uncooked corn starch, nasogastric tube

type 1b- defect in G6P transporter

• name: Pompe's Disease
• defect: lysosomal alpha 1-4
• muscle glucogenoses
• generalized- affects heart, liver, and muscles
• glycogen buildup in lysosomes
• affects brain and spinal cord
• 3 types: infantile, juvinille, adult
• *severe

• name: Cori's Disease
• defect: amylo 1-4 glucosidase debranching enzyme
• mild
• glycogen molecules have short outter branches so unable to metabolize beyond branch points

• name: Ander's Disease
• defect: glycogen branching enzyme
• *severe and fatal
• long chains are insoluble
• liver cirrhosis
• autoimmune attack on tissues
• very rare
• requires liver transplant

• name: McArdle
• defect: muscle phosphorylase
• muscle glycogenosis
• cramping upon exercise
• CKMM levels rise because of muscle proteolysis
• myoglobinuria (red urine)
• treatment- high protein diet w creatine

• name: Her's Disease
• defect: liver phosphorylase
• hypoglycemia and hepatomegaly

• name: Tarui's Disease
• defect: PFK-1 enzyme
• muscle weakness
• hemolysis due to low PFK activity in RBCs

• defect: glycogen synthase
• no glycogen is produced
• fluctuates b.w hyper and hypoglycemia

inhibits aldolase B; normal rxn : F1P --> [ald B] --> DHAP + glyceraldehdye

• -causes low ATP, which stimulates AMP which activates AMP deaminase to produce NH3 + IMP
• this reaction releases Pi to help produce energy, but does more harm than good becausethe NH3 forms uric acid leading to hyperurecemia

• fructosuria
• 1st seen when weaning baby
• fructosuria
• hypoglycemia
• lactic acidosis
• jaundice
• hepatosplenomegaly

• aka Essential Fructosemia
• normal reaction: Fructose -->[FK] ---> F1P
• inhibits FK
• not serious

G6P --> [G6PD] --> glucose6phospholactone

-deficiecny in G6PD halts this rxn so there is no release of NADH

decreased NADPH leads to a decreased reduced glutothione pool so increase in oxidative stress from ROS

400 types of mutations of this gene, most commin in places where there is malaria

• I- most severe- chronic hemolytic anemia
• II- severe- bouts of acute hemolytic anemia
• III- moderate - neonatal jaundice
• IV- no symptons- majority of anemias

• due to a defective beta subunit of the NADPH oxidase complex so it cant produce superoxides or fight infection
• causes recurrent life threatening bacterial and fungal infections
• granulomas often found in skin, GI tract and UT
• granuloma- collection of macrophages

• caused by lack of protein in the diet, and therefore lack of albumin
• albumin is (-) and attracts Na+ drawing H20 into capillaries but w/o it, the stomachswells

presence of stones within the lumen of the gallbladder (mostly composed of cholesterol) due to high cholesterol, or low bile salt levels

excessive lipid in feces (gray discoloration)

• Primary Lactose Intolerance: due to low expression of beta-galactosidase (lactase)
• Secondary Lactose Intolerance: due to severe intestinal injury or loss of absorptive villi cells that secrete lactase [celiac disease, diarrhea, gastroenteritis ]
• Congenital Lactose Deficiency (alactasia): severe, rare

• individuals with high levels of uric acid in blood
• purines --> uric acid --> urinated
• if not urinated, forms sodium urate crystals in tissues and then inflames