Biochem Flashcards
Vitamin A is also called
retinol
Vitamin A deficiency
Night blindness (nyctalopia); dry, scaly skin (xerosis cutis); corneal degeneration (keratomalacia); Bitot spots on conjunctiva; immunosuppression
Vitamin B1 is also called
thiamine
Vitamin B1 deficiency
Impaired glucose breakdown
Wernicke-Korsakoff syndrome, beriberi
Vitamin B1 function
Cofactor for dehydrogenase enzyme reactions
Think ATP: α-ketoglutarate dehydrogenase, Transketolase, and Pyruvate dehydrogenase
Wernicke-Korsakoff syndrome
Vit B1 deficiency
Confusion, ophthalmoplegia, ataxia (classic triad) + confabulation, personality change, memory loss (permanent). Damage to medial dorsal nucleus of thalamus, mammillary bodies
Dry beriberi
polyneuritis, symmetrical muscle wasting
Wet beriberi
high-output cardiac failure (dilated cardiomyopathy), edema.
Vitamin B2 is also called
riboflavin
B2 function
Component of avins FAD and FMN, used as cofactors in redox reactions
(FAD and FMN are derived from riboFlavin)
B2 deficiency
Cheilosis (in ammation of lips, scaling and ssures at the corners of the mouth), Corneal vascularization
Vitamin B3 is also called
niacin
B3 function
Constituent of NAD+, NADP+ (dehydrogenase enzymes) Derived from tryptophan. Synthesis requires vitamins B2 and B6
B3 deficiency
Pellagra: 3 D’s
Diarrhea
Dementia (also hallucinations)
Dermatitis (C3/C4 dermatome circumferential “broad collar” rash [Casal necklace], hyperpigmentation of sun- exposed limbs)
Hartnup disease
AR; Defciency of neutral amino acid (eg, tryptophan) transporters in proximal renal tubular cells and enterocytes
Decreased tryptophan for B3: pellagra-like
Treat w/ high protein diet and nicotinic acid
Vitamin B5 is also called
pantothenic acid
Vitamin B5 function
Essential component of coenzyme A (CoA, a cofactor for acyl transfers) and fatty acid synthase
Vitamin B5 deficiency
Dermatitis, enteritis, alopecia, adrenal insufficiency
Vitamin B6 is also called
pyridoxine
Vitamin B6 function
Converted to pyridoxal phosphate (PLP):
cofactor in transamination (eg, ALT and AST), decarboxylation reactions, glycogen phosphorylase
Synthesis of cystathionine, heme, niacin, histamine, and NTs: serotonin, epic, NE, dopamine, and GABA
Vitamin B6 deficiency
Convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemias due to impaired hemoglobin synthesis and iron excess
Vitamin B7 is also called
biotin
Vitamin B7 function
Cofactor for carboxylation enzymes
Vitamin B7 deficiency
Relatively rare. Dermatitis, alopecia, enteritis. Caused by antibiotic use or excessive ingestion of raw egg whites
Vitamin B9 is also called
folate
Vitamin C deficiency
Scurvy—swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, “corkscrew” hair.
Weakened immune response.
Vitamin E deficiency
Hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demyelination
Result of DNA methylation, histone methylation and acetylation
DNA methylation: silences DNA (mute)
Histone methylation: mute
Histone acetylation: active
Leflunomide
inhibits dihydroorotate dehydrogenase (disrupts pyrimidine synthesis)
Adenosine deaminase deficiency
↑ dATP: toxic to lymphocytes
Seen in AR SCID
DNA polymerase III
Prokaryotes
5 to 3 synthesis with 3 to 5 exonuclease activity
DNA polymerase I
Excises RNA primer with 5′ to 3′ exonuclease.
Gene regulators located close, far or in an intron from the gene
Enhancers and silencers
α-amanitin
Found in mushrooms: inhibits RNA polymerase II
Severe hepatotoxicity
Actinomycin D
Inhibits RNA polymerase in both prokaryotes and eukaryotes.
Antibodies to spliceosomal snRNPs
aka anti-Smith
SLE
Anti-U1 RNP antibodies
Associated with mixed connective tissue disease
Site of synthesis of secretory (exported) proteins
RER
Site of steroid synthesis and detoxification of drugs and poisons
SER
Site of synthesis of cytosolic and organellar proteins
Free ribosome
I-cell disease pathology
Lysosomal storage disorder; defect in N-acetylglucosaminyl-1-phosphotransferase
Golgi doesnt phosphorylate mannose-6-p residues; proteins sent to EC instead of lysosome
I-cell disease presentation
Coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes
COPI and COPII
I: retrograde and cis-golgi to ER
II: anterograde
(II steps forward, I step back)
Zellweger syndrome
Peroxisome disease
hypotonia, seizures, hepatomegaly, early death
Refsum disease
Peroxisome disease
Scaly skin, ataxia, cataracts/night blindness, shortening of 4th toe, epiphyseal dysplasia
Type I collagen
bONE, skin, tendon, dentin, cornea
Type II collagen
Cartilage
Type III collagen
Reticulin
Type IV collagen
Basement membrane, basal lamina, lens
Osteogenesis imperfecta type I defect
↓ production of type I collagen
Alport syndrome defect
Defective type IV collagen
Defect in scurvy
hydroxylation of specific proline and lysine residues to make collagen
Defect in Ehlers-Danlos
cleavage of disulfide-rich terminal regions of procollagen to insoluble tropocollagen
Genes in osteogenesis imperfecta; most common type
COL1A1 and COL1A2
AR with decreased amounts of normal type I
Presentation of osteogenesis imperfecta
Fractures, blue sclera, dental changes, hearing loss
Genes of classic ED
mutation in type V collagen (COL5A1, COL5A2)
Presentation of ED
hyperextensible skin, tendency to bleed (easy bruising), and hypermobile joints
Menkes disease inheritance and cause
XL-R
Impaired copper absorption and transport d/t defective Menkes protein (ATP7A): ↓ activity of lysyl oxidase
Menkes presentation
Brittle, “kinky” hair, growth retardation, and hypotonia
Marfan syndrome genetics and cause
AD; FBN1 gene mutation on chromosome 15 → defective fibrillin (glycoprotein that forms a sheath around elastin)
Marfan presentation
Tall with long extremities;
Pectus carinatum;
Hypermobile joints;
Long, tapering fingers and toes (arachnodactyly);
Cystic medial necrosis of aorta; aortic incompetence and dissecting aortic aneurysms;
Floppy mitral valve
Subluxation of lenses; upward and temporally
McCune-Albright syndrome
Mutation of G-protein signaling
Unilateral café-au-lait spots with ragged edges, polyostotic brous dysplasia, and at least one endocrinopathy
Survivable only if mosaicism is present
Locus heterogeneity
Mutations at different loci can produce a similar phenotype
Allelic heterogeneity
Different mutations in the same locus produce the same phenotype
Heteroplasmy
Normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease
Genetics of CF
AR; CFTR gene on chromosome 7
Deletion of Phe508
Newborn screen for CF
↑ immunoreactive trypsinogen
Complications of CF
Pulmonary infections, pancreatic insufficiency, fat malabsorption, biliary cirrhosis, liver dz, nasal polyps, clubbing of nails
Meconium ileus in newborns
Infertiblity in men (no vas deferens)
ECF changes in CF
Analagous to a loop diuretic
Loss of Na/H20 and renal K/H wasting
Duchenne muscular dystrophy
XL d/t frameshift
Weakness begins in pelvic girdle muscles and progresses superiorly.
Pseudohypertrophy of calf muscles
Becker muscular dystrophy
XL d/t non-frameshift deletion
Myotonic type I muscular dystrophy
AD; CTG expansion in DMPK gene
- Abnormal expression of myotonin protein kinase
- Myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia
Fragile X
XL-D; CGG expansion in FMR (leads to hypermethylation)
-Post-pubertal macroorchidism, long face with large jaw, large everted ears, autism, MVP
Cri-du-chat syndrome
Congenital microdeletion of short arm of chromosome 5
-Microcephaly, moderate to severe intellectual disability, high-pitched crying/ meowing, epicanthal folds, cardiac abnormalities (VSD)
Williams syndrome
Congenital microdeletion of long arm of chromosome 7 (elastin gene)
“elfin” facies, intellectual disability, hypercalcemia, friendly, CV problems
DiGeorge syndrome
22q11 deletion
thymic, parathyroid, and cardiac defects
Velocardiofacial syndrome
22q11 deletion
palate, facial, and cardiac defects
Zinc deficiency
Delayed wound healing, hypogonadism, ↓ adult hair
Kwashiorkor
Protein malnutrition resulting in skin lesions, edema, liver malfunction, anemia
Marasmus
Malnutrition not causing edema
Deficient in calories
Fomepizole
inhibits alcohol dehydrogenase and is an antidote For Overdoses of Methanol or Ethylene glycol
Effects of EtOH metabolism
↑ NADH/NAD
Pyruvate → lactate (lactic acidosis)
Oxaloacetate → malate (prevents gluconeogenesis fasting hypoglycemia)
Dihydroxyacetone phosphate → glycerol- 3-phosphate (combines with fatty acids to
make triglycerides hepatosteatosis)
Essential fructosuria
AR; defect in fructokinase
Fructose appears in blood and urine; benign and asymptomatic
Fructose intolerance cause
AR; deficiency of aldolase B
Fructose-1-phosphate accumulates: decreased phosphate: inhibition of glycogenolysis and gluconeogenesis
Fructose intolerance presentation
Following consumption of fruit, juice, or honey
Hypoglycemia, jaundice, cirrhosis, vomiting
Galactokinase deficiency inheritance and presentation
AR; Galactitol accumulates if galactose is in diet
Mild: galactose in blood and urine; infantile cataracts
Failure to track objects or to develop a social smile
Classic galactosemia
AR; Absence of galactose-1-phosphate uridyltransferase
Failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability
Predisposition to E. coli
Exclude galactose and lactose from diet
Aldose reductase
Converts glucose to sorbitol
Can become trapped in cell if sorbitol dehydrogenase is deficient
Cataracts, retinopathy, and peripheral neuropathy in DM
Types of cells with only aldose reductase
Lens, Retina, Kidney and Schwann cells
Glucogenic amino acids
I met his valentine, she is so sweet
Methionine (Met), histidine (His), valine (Val)
Glucogenic/ketogenic amino acids
isoleucine (Ile), phenylalanine (Phe), threonine (Thr), tryptophan (Trp).
Ketogenic amino acids
leucine (Leu), lysine (Lys)
Hyperammonemia
Excess NH3 depletes α-ketoglutarate: inhibits TCA cycle
Limit protein
Ornithine transcarbamylase deficiency
XL-r urea cycle disorder
Excess carbamoyl phosphate is converted to orotic acid
Phenylketonuria cause and dz process
AR; ↓ phenylalanine hydroxylase or BH4 (cofactor)
Tyrosine becomes essential
↑ phenylalanine: excess phenyl ketones in urine
Phenylketonuria presentation
Aromatic aa: musty body oder
Intellectual disability, growth retardation, seizures, fair skin, eczema
Maternal PKU
microcephaly, intellectual disability, growth retardation, congenital heart defects
Maple syrup urine disease cause and dz process
AR; Blocked degradation of branched amino acids (L, I, V)
↓ branched-chain α-ketoacid dehydrogenase
Maple syrup urine disease presentation
Vomiting, poor feeding, urine
smells like maple syrup/burnt sugar
Severe CNS defects, intellectual disability, and death
Alkaptonuria
AR; Congenital deficiency of homogentisate oxidase in degradative pathway of tyrosine to fumarate; homogentisic acid forms pigment in tissues
- bluish-black connective tissue, ear cartilage, and sclerae
- urine turns black
- debilitating arthralgias
Homocystinuria
↑ Homocysteine in urine, Osteoporosis, Marfanoid habitus, Ocular changes (downward and inward lens subluxation), CV effects, kyphosis, intellectual disability
Cystinuria
AR; defect of renal PCT and intestinal aa transporter: prevents reabsorption of Cystine, Ornithine, Lysine, and Arginine (COLA)
Excess cystine in the urine can lead to recurrent precipitation of hexagonal cystine stone
Von Gierke disease (type I)
Glucose-6-phosphatase deficiency
Severe fasting hypoglycemia; ↑↑ glycogen in liver, ↑ blood lactate, triglycerides, uric acid
Hepatomegaly
Pompe disease (type II)
Lysosomal acid α-1,4- glucosidase with α-1,6- glucosidase deficiency
Cardiomegaly, hypertrophic cardiomyopathy, hypotonia, exercise intolerance: early death
Cori disease (type III)
Debranching enzyme (α-1,6 -glucosidase) deficiency Milder form of von Gierke: normal blood lactate Accumulation of limit dextrin–like structures in cytosol
McArdle disease (type V)
Skeletal muscle glycogen phosphorylase deficiency
↑ glycogen in muscle; cannot break it down: Muscle cramps, Myoglobinuria (red urine)
Tay-Sachs disease
AR; HeXosaminidase A deficiency: GM2 ganglioside buildup
Progressive neurodegeneration, developmental delay, “cherry-red” spot on macula, lysosomes with onion skin, NO hepatosplenomegaly
Fabry disease
XR; α-galactosidase A deficiency: ceramid trihexoside buildup
Early: Triad of episodic peripheral neuropathy, angiokeratomas
Late: progressive renal failure, cardiovascular disease
Metachromatic leukodystrophy
AR; Arylsulfatase A deficiency: Cerebroside sulfate build up
Central and peripheral demyelination with ataxia, dementia
Krabbe disease
AR; Galactocerebrosidase deficiency: Galactocerebroside, psychosine build up
Peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy, globoid cells
Gaucher disease
AR; Glucocerebrosidase deficiency
Hepatosplenomegaly, pancytopenia, osteoporosis, avascular necrosis of femur, bone crises, Gaucher cells
Niemann-Pick disease
AR; Sphingomyelinase deficiency
Progressive neurodegeneration, hepatosplenomegaly, foam cells, “cherry-red” spot on macula
Hurler syndrome
AR; α-l-iduronidase deficiency: Heparan sulfate and dermatan sulfate build up
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
Hunter syndrome
XR; Iduronate sulfatase, heparin and dermatan sulfate buildup
Mild Hurler + aggressive behavior, no corneal clouding
Alternative to Niacin in NAD synthesis?
Tryptophan
What does the dermatitis of pellagra look like?
Rough, thick, scaly
Worse with sun exposure
Where is K excreted in the kidney?
collecting duct
Fungus that forms budding yeast with germ tubes
Candida
SE of theophylline OD
N/V, abd pain, diarrhea, cardiac arrhythmia, SZ
Glycogen in lysosomes in indicative of
Pompe disease (defect in alpha glucosidase aka acid maltase)
What molecule has the same precursor as beta endorphins?
ACTH
What does degradation of LCFAs require?
Carnitine-dependent transport into the mitochondrial matrix
What does fatty acid synthesis require?
Transport of citrate from mitochondria to cytosol
Systemic 1° carnitine deficiency
LCFAs cannot be transported into mitochondria: toxic accumulation
Weakness, hypotonia, and hypoketotic hypoglycemia
Medium-chain acyl-CoA dehydrogenase deficiency
↓ breakdown of FA into acetyl CoA; accumulation of FA carnitines in blood → hypoketotic hypoglycemia
Vomiting, lethargy, seizures, coma, liver dysfunction
What causes buildup of ketone bodies?
Fasting/DM: oxaloacetate is depleted for gluconeogenesis
EtOH: excess NADH shunts oxaloacetate to malate.
Both lead to build up of acetyl-CoA, which shunts glucose and FFA toward production of ketone bodies
Maintenance of blood glucose in 1-3 days of starvation
- Hepatic glycogenolysis
- Adipose release of FFA
- Muscle and liver shift to FFA
- Hepatic gluconeogenesis
Maintenance of blood glucose in >3days of starvation
Adipose stores: ketone primary energy source
Last: vital protein degradation
What degrades dietary triglycerides and where?
Pancreatic lipase
In the small intestine
What degrades TGs circulating in chylomicrons and VLDLs?
LPL
What degrades TGs remaining in IDL?
Hepatic TG lipase (HL)
What degrades TGs stored in adipocytes?
Hormone-sensitive lipase
Abetalipoproteinemia cause
AR; Chylomicrons, VLDL, LDL absent
Deficiency in ApoB48, ApoB100
Abetalipoproteinemia presentation
Infant: severe fat malabsorption, steatorrhea, failure to thrive
Adult: retinitis pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, progressive ataxia, acanthocytosis
Treatment for abetalipoproteinemia
Restriction of long-chain fatty acids, large doses of oral vitamin E
Hyperchylomicronemia (I)
AR; Lipoprotein lipase or apolipoprotein C-II
deficiency
↑ Chylomicrons, TG, cholesterol
Pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas, creamy supernatant
Familial hyper- cholesterolemia (II)
AD; Absent or defective LDL receptors
Accelerated atherosclerosis, tendon (Achilles) xanthomas, and corneal arcus
Dysbeta-lipoproteinemia (III)
AR; Defective ApoE
↑ Chylomicrons, VLDL
Premature atherosclerosis, tuberoeruptive xanthomas, xanthoma striatum palmare
Hyper-triglyceridemia (IV)
AD; Hepatic overproduction of VLDL
↑ VLDL, TG
Hypertriglyceridemia; acute pancreatitis
