Biochem Flashcards
Phosphofuctokinase-1
RL step in glycolysis
Upregulators: AMP, fructose-2,6-bisphosphae
Downregulators: ATP, citrate
Fructose-1,6-bisphosphatse
RL step in gluconeogenesis; occurs at same location as PFK-1 in glycolysis
Up: ATP, acetyl-CoA
Down: AMP, fructose-2,6-bisphosphatase
Glycolysis steps that produce ATP
Phosphoglycerate kinase
Pyruvate kinase
Up: Fructose-1,6-bisphosphate
Down: ATP, alanine
Phosphofructokinase-2
Forms fructose-2,6-bisphosphate from F6P
-This product upregulates glycolysis
Up: Phosphorylation (caused by glucagon =» increased cAMP =» increased PKA)
Ketogenic diet
Needed for babies/pts. w/ pyruvate dehydrogenase deficiency; pts. get a buildup of lactate and alanine
Clinical: Neurologic deficits, lactic acidosis, increased alanine
Tx: Increased leucine and lysine in diet (ketogenic AAs) or high fat diet
Interference w/ Complex IV of the ETC
CN-; CO
-Decreases proton gradient and blocks ATP synthesis
Brown fat
Produces thermogenin which is an ETC uncoupler (decreases proton gradient)
- Produces heat
- Dinitrophenol (used for weight loss) and aspirin (fever w/ OD) also produce this effect
Classic galactosemia
Galactose-1-phosphate uridyltransferase deficiency
Clinical: Failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
-Galactokinase deficiency presents as a milder version with only signs being reducing sugar in urine and faint cataracts
Aldose reductase
Converts glucose to sorbitol
Is a problem in cells with constitutive glucose uptake like retinal cells and the kidney
Carbamoyl phosphate synthetase I
Converts NH4+ to carbamoyl phosphate
-Reacts with Ornithine in the mitochondria to make citrulline
⭐️Enzyme requires n-acetylglutamate
Two options for Pyruvate under hypoxic conditions
Converted to lactate or alanine
Hyperammonemia Tx (3 things)
Rifaximin - decreases colonic ammoniagenic bacteria
Lactulose - traps NH4
Avoid protein in diet
Increased Orotic acid in urine BUT no Megaloblastic anemia
Ornithine Transcarbomylase deficiency; since Citrulline can’t be formed, carbamoyl phosphate is broken down to orotic acid
Presents in first few days of life as ammonia intoxication
️Enzyme deficiency in albinism
Tyrosinase
Musty body Oder
PKU; disorder of aromatic AA metabolism leading to toxic buildup, also possibly due to BH4 deficiency
Clinical: Intellectual disability
Growth retardation
Seizures
Eczema, fair skin
Tx: Avoid Phe in diet (artificial sweeteners), supplement tyrosine
(+) urinary cyanide-Nitroprusside test
Cystinuria
-Renal PCT inability to reabsorb cysteine, Ornithine, lysine, and arginine (COLA)
Tx: urinary alkalinization, Acetazolamide, hydration
Glucose-6-phosphatase deficiency
Von-Gierke’s Disease; pts. must avoid fructose and galactose
Clinical: Severe fasting hypoglycemia, increased glycogen, increased lactic acid, increased uric acid, increase triglycerides, hepatomegaly
Lysosomal a-1,4-glucosidase deficiency
“Acid maltase”
Pompe disease
Clinical: Cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance
*AT RISK FOR EARLY DEATH
a-1,6-glucosidase deficiency
Cori Disease; gluconeogenesis intact but pts. can’t debranch glycogen
Clinical: Mild hypoglycemia, mild hepatomegaly, mild uric acidemia, normal lactic acid
Glycogen phosphorylase deficiency
Mcardle’s Disease
Clinical: Exercise intolerance (muscle cramps), myoglobinuria, electrolyte abnormalities
Tx: Vit B6
a-galactosidase A deficiency
Fabry disease
Clinical: Peripheral neuropathy of hands and feet, angiokeratomas, CVD
- Increased ceramide trihexoside
- XLR inheritance***
Glucocerebrosidase deficiency
Gaucher’s Disease; causes accumulation of glucocerebroside
Clinical: Hepatosplenomegaly, pancytopenia, aseptic necrosis off fthe femur
*Chicken-scratch monos
Sphingomyelinase deficiency
Niemann-Pick Disease; accumulation of sphingomyelin
Clinical: Progressive neurodegeneration, HEPATOSPLENOMEGALY (as opposed to?), foam cells, cherry-red macula
Hexosaminidase A deficiency
Tay-Sach’s Disease; accumulation of GM2 ganglioside
Clinical: Progressive neurodegeneration, cherry-red macula, developmental delay
Galactocerebrocidase deficiency
Krabbe’s disease; accumulation of galactocerebroside
Clinical: Peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Arylsulfatase A deficiency
Metachromatic leukodystrophy; accumulation of cerebroside sulfate
Clinical: Ataxia, dementia (due to demyelination of CNS and PNS)
a-L-iduronidase deficiency
Hurler Syndrome; accumulation of heparan and dermatan sulfate (mucopolysaccharides)
Clinical: Developmental delay, gargoylism (coarse facial features), corneal clouding (as opposed to), hepatosplenomegaly
Iduronate sulfatase deficiency
Hunter Syndrome; accumulation of heparan and dermatan sulfate (mucopolysaccharides)
Clinical: Mild hurlers + AGGRESSIVENESS
*Hunters see clearly and angrily aim for the X”
XLR inheritance
Medium-chain acyl-CoA dehydrogenase deficiency
Inability to break down theses FAs; presents as hypoketotic hypoglycemia w/ seizures, coma
AVOID FASTING STATES
-Similar to carnitine deficiency BUT carnitine is LCFAs (why?)
Lipoprotein Lipase deficiency
Familial hyperchlomicronemia; increased serum chylomicrons, TG, and cholesterol
Clinical: Pancreatitis, hepatosplenomegaly, pruritic xanthomas
***Creamy layer in supernatant
Defective LDL receptors
Familial hypercholesterolemia; increased serum LDL and cholesterol
Clinical: Accelerated atherosclerosis (MI prior to 20 possible), tendonous xanthomas, corneal arcus (white ring on the periphery of the iris)***
Hepatic overproduction of VLDL
Hypertriglyceridemia; increased serum VLDL and TGLs
Clinical: Acute pancreatitis; serum TGL increase
AD inheritance*
Chlordiazepoxide
Benzodiazepine
Clomipramine
TCA that can successfully treat OCD in children and adults
TGF-B receptor
Receptor serine/threonine kinase
Long term dialysis complication
Amyloidosis consisting of B2-microglobulin
Increased Rhine hydroxyproline
Indicates increased bone resorption by osteoclasts
Bone repair
- Ruptured blood vessels form a hematoma bridging the fracture gap
- (1 week) Soft tissue callus anchors the fracture
- Osetoblasts deposit immature woven bone
- will see irregularly arranged collagen
- Hyaline cartilage forms at periphery and undergoes endochondral ossification
⭐️”bony callus” - Bony callus turns to mature lamellar bone
Areas with no BBB
Median eminence, area postrema, choroid plexus, pineal gland, neurohypophysis
Phase I Reactions
Include oxidation, desulfuration, epoxide formation, hydoxylation
Monoamine oxidase can locally hydrolyze some drugs as well
Chenocholic acid/ Cholic acid
First product formed in production of bile salts; these are increased alongside bile salts w/ increased prod.
Hepatic Stellate Cells
Found in the perisinusoidal space (space of Disse) and secrete type I collagen
***Very important in hepatic scarring and portal HTN
General concepts of hepatic zone necrosis
Zone 1 =» Few toxins, chronic hepatitis
Zone 2 =» Yellow fever
Zone 3 =» Ischemia, Right-sided HF, CCl4, amantin, copper, acetominophen (go to guess)
Microvesicular steatosis causes
Tetracycline, VA
