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What is the structure of chromatin? Heterochromatin? Euchromatin?

Beads on a string. Histone octamer=2 x (H2A, H2B, H3, H4). DNA string. H1 bound to nucleosome (histone) and DNA.

HC=Highly condensed. Inactive

Euchromatin=active, truly transcribed.


What is the purpose of DNA methylation? At CpG islands? Histone methylation? Acetylation?

DNA methylation helps it be recognized by mismatch repair enyzmes

At CpG islands=mute

Histone methyl=mute



Which nucleotides are purines? How are purines made? What substances are required?

PURe As Gold (adenosine, glycine)

Ribose 5-P is turned into PRPP by PRPP synthetase.
A base is then added to form IMP.
IMP can be converted to AMP or GMP.


Which NTs are pyrimidines? Structure? How are they made? Requirements?

CUT the PY=cytosine, uracil, thymidine

Pie is sweet-requires carbamoyl phosphate and aspartate.

A pie is a circle-only one ring

Glutamine and CO2 are converted to carbamoyl phosphate by CPS-II.
Aspartate is added to make orotic acid.
PRPP is added to orotic acid to form UMP.
UMP is converted to UDP
UDP can be converted to CTP.
UDP can also be converted to dUDP by ribonucleotide reductase
dUDP is converted to dUMP which is converted to dTMP by thymidylate synthase which requires THF.
DHF is converted to THF by DHFR.


Describe the purine salvage pathway.

AMP is converted to adenine by APRT.
It can also be converted to adenosine.
Adenosine is converted to Inosine by ADA.
Inosine is conv. to hypoxanthine.
Hypoxanthine can be converted to IMP by HGPRT
It can also be converted to xanthine by XO
GMP is converted to guanosine then guanine.
Guanine can be converted to GMP by HGPRT
It can also be converted to xanthine.
Xanthine is converted to uric acid by xanthine oxidase
Uric acid is excreted in the urine.


What is adenosine deaminase deficiency? Pathophys? Consequences?

Excess ATP leasd to NT imbalances, descrease lymphocyte count. Major cause of SCID.


Symptoms of Lesch-Nyhan? Pathophys?

Absent HGPRT

Hyperuricemia, gout, pissed off (aggression/self-mutilation), retardation, dystonia)


What are the differences between DNAP III and DNAP I. Direction of DNA, RNA, and protein synth? mRNA read?

III has 5' to 3' synth and 3' to 5' exonuclease (proofreading)

I has 5' to 3' exonuclease for RNA primer.

5' to 3' and N to C


Describe the lac operon and how and when it leads to lactose metabolism

Low glucose leads to adenylyl cyclase leads to cAMP leads to CAP which leads to transcription of lactose metabolism proteins.

High lactose leads to an unbinding of a repressor protein from the operator site which leads to increase transcription.


In what phase does NT excision repair occur? What does a defect lead to? Same questions for mismatch repair? What does a defect of nonhomologous end joining lead to?

NT excision=G1=xeroderma pigmentosum


non homologous=ataxia telangiectasia, fanconi anemia, BRCA?


What does M6P signal? Where does it occur? Where does n-linked oligosaccharide addition occur? What does COP I do? COPII? Clathrin?

Trafficking to lysosome. Golgi

oligosaccharide addition-RER

COPI-Retrograde along golgi, golgi to ER
COPII-ER to golgi
Clathrin-trans golgi to lysosomes or plasma membrane, PM to endosomes


What is the role of the peroxisome?

catabolism of VLCFA, branched chain FAs, and AAs.


What are the function of microfilaments? What is an example? Same questions for intermediate filaments (examples)? Same questions for microtubules. What immunohistochemical stain is used for the various intermediate filaments/tissue location?

Micro-muscle contr., cytokinesis=actin

intermediate-maintain cell structure=vimentin (CT), Desmin (muscle), cytokeratin (epithelial), GFAP (neuroglial), neurofilaments (Neurons)

microtubules-movement, cell division=cilia, flagella, mitotic spindle, axonal trafficking, centrioles


What is the structure of cilia? What is kartagener syndrome? Another name? symptoms?

9+2 arrangement of microtubule doublets

Primary ciliary dyskinesia. No axonemal dynein which links doublets.

Male and female infertility (sperm and fallopian tube), increased risk of ectopic, bronchiectasis, recurrent sinusitis, and situs inversus.


Which types of collagen make up the different tissues?

Be (So Totally) Cool, Read Books

type I=bone, Skin, tendon
III=reticulin (blood vessels)
IV=basement membrane


Describe the various steps of collagen synth, where they occur, and what can go wrong with each step.

synth (RER)=Translation of alpha chains, usually gly, pro, lys

Hydroxylation of pro/lys=Vit. c needed (scurvy).

Glycosylation=allows the formation of the triple helix of 3 alpha chains (OI)

Exocytosis from RER and cell into EC space

Proteolytic processing=cleavage of disulfide bonds forming tropocollagen

Cross-linking=covalent lysine-hydroxylysine crosslinkage by copper containing lysyl oxidase to make collagen fibrils. (Ehlers-Danlos and Menkes)


What is the genetics of OI? Pathophys? Symptoms?


Decreased production of normal type I collagen (can't form triple helix)

multiple fractures, blue sclerae, hearing loss, dental imperfections.


symptoms of ehlers-danlos? Types/collagen involved? pathophys?

hyperextensible skin, tnedency to bleed, hypermobile joints.

Berry and aortic aneurysms, organ rupture

hypermobility type (most common)

Classical type=both skin and joint (type V collagen)

VAscular type (vascular and organ rupture)=type III collagen


What are the genetics of Menkes disease? Pathophys? Symptoms?

X linked

Impaired copper absorption and transport due to defective menkes protein (ATP7A)--->less lysyl oxidase.

Brittle kinky hair, growth retardation, and hypotonia


What do southern/northern/western/southwestern blot quantify?


Southwestern=DNA-binding proteins


What is the difference between a direct ELISA and an indirect ELISA?

Direct ELISA-test antibody connected to a color generating enzyme to see if a specific antigen is present

Indirect ELISA-test antigen or antibody used to see if a specific antibody or antigen is present. Another antibody coupled to a color generating enzyme then checks to see if the test antigen or antibody bound.


What can karyotyping be performed on? How does FISH work?

Bone marrow, amniotic fluid, placental tissue

flourescent DNA/RNA probe binds to a gene site on a chromosome. Localization of genes/anomalies.


What is codominance?* Variable expressivity? Incomplete penetrance? Pleiotropy? Anticipation?* Loss of heterozygosity?* Dominant negative mutuation? Linkage disequilibrium? Mosaicism?* Locus heterogeneity?* Allelic heterogeneity?* Heteroplasmy? Uniparental disomy?* Imprinting?* Examples of each?*

codominance? both allelles contribute to phenotype=ABO, alpha 1 antitrypsin

Variable expressivity? phenotype varies with same genotype

Incomplete penetrance? Not all individuals with genotype show phenotype

Pleiotropy? One gene leads to multiple phenotypic effects.

Anticipation? Increased severity over generations; trinucleotide repeats

Loss of heterozygosity? patient develops a mutaiton in a tumor suppressor gene, the complementary allele must be deleted before cancer develops. Not true of oncogenes.

Dominant negative mutuation? Exerts a dominant effect. A heterozygote produces a non-functional altered protein that also prevents normal protein from functioning.

Linkage disequilibrium? Certain alleles at 2 linked loci to occur together more or less often than expected by chance. Measured in populations, not families.

Mosaicism? Genetically distinct cell lines in same individual. Somatic=after fertilization, propagates through multiple tissues. Gonadal=only in egg or sperm cells (future generations)=McCune Albright

Locus heterogeneity? Similar phenotype due to mutations at different loci. Albinism.

Allelic heterogeneity? Different mutations in the same locus produce the same phenotype. Beta thalassemia

Heteroplasmy? Normal and mutated mtDNA, resulting in variable expression in mitochondrially inherited disease.

Uniparental disomy? Offspring received 2 copies of a chromosome from one parent and no copies from the other

Imprinting? At some loci, only one allele is active. The other is inactive. With one allele inactivated, if the active allele is deleted--->disease. Prader Willi and Angelman=chromosome 15.


What is hardy weinberg genetics? When do they apply? How are they adapted in x-linked recessive diseases?

p^2 + 2pq + q^2=1 and p+q=1.

2pq = heterozygosity

p^2 and q^2 =homozygous

The frequency of x-linked recessive disease in males is q and in females is q^2.

No mutations occurring, no net migration, completely random mating.


What is the pathophys of prader-willi? Symptoms? Same questions for angelman?

Prader-Willi=Paternal gene deleted, hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia.

AngelMan Syndrome=Maternal gene deleted. Happy puppet=inappropriate laughter, seizures, ataxia, and severe intellectual disability.


What are mitochondrial myopathies like? Cause?

Heteroplasmy. Rare. Myopathy, lactic acidosis, and CNS disease. Secondary to failure in oxidative phosphorylation. Muscle biopsy shows ragged red fibers.


What are some x linked recessive disorders?

Be Wise, Fool's GOLD Heeds Silly HOpe

Bruton's agammaglobulinemia, Wiskotts aldrich, fabry disease, G6PD, ocular albinism, lesch-nyhan, duchenne and becker muscular dystrophy, hunter syndrome, Hemophilia A and B, and Ornithine transcarbamylase deficiency


What are the genetics of duchenne muscular dystrophy? pathophys? Symptoms? Age? complications? Diagnosis? How does becker differ from Duchenne?

X linked-frameshift

Truncated dystrophin, loss of anchoring-->myonecrosis

Weakness beginning in pelvic girdle muscles, progresses up. Pseudohypertrophy of claves (fibrofatty replacement),

Gower maneuver, waddling gait.

Onset before age 5

Dilated cardiomyopathy

Increased CPK and aldolase; Western blot and muscle biopsy


X-linked-non frameshift insertions into dystrophin gene.

Less severe, onset in adolescence


Genetics of myotonic type I muscular dystrophy? Pathophys? Symptoms?

AD. CTG trinucleotide repeat expansion in the DMPK gene--->abnormal expression of myotonin protein kinase--->My Tonia, My Testicles (atrophy), My Toupee (frontal balding), and My Ticker (arrhythmia) , cataracts.


What is the inheritance of fragile x? Which gene is involved? What is the mutation like? What are the findings?

Extra large testes, jaw (with long face), ears

Autism, Mitral valve prolapse


X linked-CGG repeat-FMR1 gene.


What are 4 trinucleotide repeat expansion diseases? What patterns of NTs are in each? What are the genetics like?

Try Hunting for my fried eggs (Trinucleotide: Huntingtons, myotonic type musc dyst, friedrichs ataxia, fragile X)

Fragile X, Huntingtons, and myotonic dystrophy are each C-blank-G

Friedrichs is GAA.

X-Girlfriends First Aid Helped Ace My Test (Fragile X=CGG, Friedrich=GAA, Huntingtons=CAG, Myotonic=CTG

May show anticipation


What are some symptoms/associations of down syndrome? Chromosome involved? Same questions for Edwards? Same questions for Patau? How are the 3 differentiated during pregnancy screening?

DS=chromosome 21 (Drinking age starts with D)

intellectual disability, gap b/w first 2 toes, duodenal atresia, hirschsprungs, ASD, Brushfield spots, alzheimers, ALL and AML.

First tri U/S=incr. nuchal translucency, hypoplastic nasal bone, decr. serum PAPP-A, free beta hCG is incr.
2nd tri quad screen=decr. alpha fetoprotein, incr. beta hcg, decr. estriol, and incr. inhibin A

Edwards=chromsome 18 (election age starts with E)

Intell. disabil., rocker bottom feet, small jaw, low set ears, clenched hands with overlapping fingers, prominent occiput, congenital heart disease, death within a year

1st tri=PAPP=A and beta hcg are decreased
Quad=decr. alpha fetoprotein, decr beta hcg, decr. estriol and decr. or normal inhibin

Patau=chromosome 13 (puberty starts with P)

intell. disabil, rock bottom feet, micropthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease, cutis aplasia. Death in first year

1st tri=decr. free beta hcg, decr PAPP-A, and incr. nuchal translucency.


What are the findings of Cri-Du-Chat? What part of the genetic code is involved?

Congenital microdeletion of short arm of chromosome 5.

Microcephaly, moderate to severe intellectual disability, high pitched mewing/crying, epicanthal folds, cardiac abnormal (VSD)


What are the findings in Williams Syndrome? What part of the genetic code is involved? Which gene is affected?

Congenital microdeletion of long arm of chrom. 7 (part of elastin gene)

Elfin facies, intellectual disabil, hypercalcemia (incr.sens. to vit. D), well developed verbal skills, extreme friendliness with strangers, and CV problems.


What are the symptoms of 22q11 deletion syndromes both individually and collectively? What part of the body is involved?

CATCH 22=cleft palate, abnormal facies, thymic aplasia, cardiac defects, and hypocalcemia secondary to parathyroid aplasia

3rd and 4th pharyngeal pouches

DiGeorge=hypocalcemia, thymic aplasia, and cardiac defects

Velocardiofacial syndrome=palate, facies, and cardio


What is the function of Vit. A? Another name? What occurs in defiency? What is it used to treat? What is the main worry with excess?


Part of visual pigments
Differentiation of epithelial cells into specialized tissue (prevents squamous metaplasia)

Used to treat measles, AML subtype M3, wrinkles, and acne

Nightblindness (nyctalopia)
dry, scaly skin (xerotis cutis)
corneal degeneration (keratomalacia)
Bitot spots on conjuctiva

In excess--->teratogenic (cleft palate, cardiac)
Before isotretinoin is prescribed for severe acne, a pregnancy test is given.


What is another name for Vit. B1? What does it help form in the body? What is the function of this substance? Describe the symptoms of wernicke-korsakoff syndrome, dry beriberi, and wet beriberi. How is the diagnosis made?

Thiamine-->TPP, a cofactor for dehydrogenase enzyme RXNs

ATP=alpha ketoglutarate dehydrogenase (TCA cycle), transketolase (HMP shunt), and pyruvate dehydrogenase (glycolysis to TCA cycle).

WK=confusion, opthalmoplegia, ataxia. Also, confab, personality change, memory loss. Damage to medial dorsal nucleus of thalamus and mammilary bodies

Dry Beriberi=polyneuritis, symmetrical muscle wasting

Wet Beriberi=high output cardiac failure (dilated cardiomyopathy), edema


What is another name for Vit. B2? What is it a component of? Function? Deficiency symptoms?

Riboflavin=FAD and FMN

cofactors in redox RXNS (succinate dehydrogenase)

2C's of B2=Cheilosis (inflamm. of lips, scaling and fissures at corners of mouth), corneal vascularization


What is another name for Vit. B3? What does it help form in the body? What is it derived from? What does its synth require? What is it used to treat? Symptoms of deficiency? What can cause deficiency?

Niacin=NAD, NADP

From tryptophan, requires B2 and B6

Used to treat dyslipidemia-lowers VLDL and raises HDL

Hartnup-decr. tryptophan absorption, malignant carcinoid syndrome (incr. tryptophan metab), and isoniazid (decr. B6).

Diarrhea, dementia, and dermatitis (broad collar)


What is another name for Vit. B6? What does it become in body? Function? What does deficiency lead to?

Pyridoxine-converted to PLP, a cofactor used in transamination (ALT and AST), decarboxylation RXNs, glycogen phosphorylase.

Synthesis of cystathionine, heme, niacin, histamine, and NTs such as serotonin, epinephrine, NE, DA, and GABA

Deficiency=convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemias.


What is another name for B7? Function?

Pyruvate carboxylase, acetyl coa carboxylase, propionyl coa carboxylase


What is another name for B9? What is it converted to? Function? What does defiency lead to? Lab findings? Waht can cause defiency?

Folate-->THF, a coenzyme for 1 carbon transfer RXNs
Synth of nitrogenous bases

macrocytic, megaloblastic anemia
hypersegmented PMNs
no neuro symptoms

Neural tube defects in preg.

Incr. homocysteine, normal methylmalonic acid levels

Phenytoin, sulfonamides, and methotrexate


What is another name for B12? Function? What causes deficiency? What does defic. lead to? Lab findings?

Cobalamin=homocystein methyltransferase and mehtylmalonyl CoA mutase

Insufficient intake (after a long while)
Lack of IF
lack of terminal ileum

Macrocytic megaloblastic anemia
Hypersegmented PMNs, paresthesias and subacute combined degeneration (dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin. Prolonged deficiency can lead to perm. nerve damage

Incr. homocystein and methylmalonic acid


What is another name for Vit. C? Functions? Used to treat? Describe scurvy. Other result of defic? Excess?

Ascorbic acid=Hydroxylation of proline and lysine in collagen synth. Necessary for DA Beta hydroxylase which converts DA to NE

Treatment for Methemoglobinemia by reducing Fe3+ to Fe2+

Scurvy=swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, corkscrew hair

excess=calcium oxalate nephrolithiasis.
Incr. risk of iron toxicity in predisposed individuals


What is the storage for of Vit. D? Active form? What is the function? Defic? Excess? When is excess seen?

25-OH D3=storage
1,25-OH2 D3=calcitriol=active

incr. intestinal absorption of calcium and phosphate.
Incr. bone mineralization

Rickets in children (bone pain and deformity)
osteomalacia in adults (bone pain and muscle weakness)

Excess=hypercalcemia, hypercalciuria, loss of appetite, stupor.
Seen in granulomatous disease.


What is another name for Vit. E? Function? Deficiency?


Antioxidant (protects RBCs and membranes from free radical damage)
Can enhance anticoag effects of warfarin

Hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract degen.


What is the function of vit. K? How is it synth? What does defic. lead to?

Cofactor for the gamma carboxylation of glutamic acid residues on various clotting factors (II, VII, IX, X, and proteins C and S). Warfarin is anti-vit. K

Synth by intestinal flora

Neonatal hemorrhage with incr. PT and aPTT but normal bleeding time.


What is the funciotn of zinc? Defic?

Essential for activity of 100+ enzymes.
Zinc Fingers

Delayed wound healing, hypogonadism, decr. adult hair, dysgeusia, anosmia, acrodermatitis enteropathica. May predispose to alcoholic cirrhosis


What are the symptoms/pathophys of kwashiorkor? Of marasmus?

Kwash=protein malnutrition resulting in skin lesions, edema, fatty liver-->dysfunction, anemia.

Small child with swollen abdomen

Marasmus=total calorie malnutrtion and muscle wasting, losss of subQ fat, and variable edema


Describe the 3 pathways to convert ethanol to acetate? What do fomepizole and disulfiram do? How are they used? Describe the effect that ethanol metabolism has on metabolism and the clinical results.

ethanol to acetaldehyde (alcohol dehydrogenase, catalase, and CYP2E1) to acetate (acetaldehyde dehydrogenase)

alcohol dehydrog uses NAD
catalase uses H2O2
Acetaldehyde dehydrog. uses NAD

Fomepizole inhibits alc. dehyd. used for methanol or ethylene glycol poison.
Disulfiram inhibits acet. dehyd. results in hangover symptoms

Increased NADH results in pyruvate to lactate (lactic acidosis, oxaloacetate to malate (prevents gluconeogenesis=fasting hypoglycemia), DHAP to G3P (G3P cobines with fatty acids to make TGs resulting in hepatosteatosis)


What metabolic steps take place in the mitochondria? In the cytoplasm? Both?

Mitochondria=beta oxidation, acetyl coa production, TCA cycle, oxidative phosph, ketogenesis

cytoplasm=gllycolysis, FA synth, HMP shunt, protein synth, steroid synth, and cholesterol synth

Both=heme synth, urea cycle, gluconeogenesis


What is NADPH a product of? What is it used in?

HMP Shunt

Anabolic processes (steroid and FA synth)
Respiratory burst
cytochrome P-450 system
Glutathione Reductase


What is Hexokinase found? Glucokinase? How do they differ?

Hexokinase=most tissues, active at low glucose-->tissue utilization

Glucokinase=liver, beta cells of pancreas, glucose is only stored in liver at high glucose (active at high glucose)


What is the pathophys of pyruvate dehydrogenase complex deficiency? genetics? Findings? Treatment?

Build up of pyruvate leading to lactate and alanine.


Neuro defects, lactic acidosis, incr. serum alanine starting in infancy

Increase intake of ketogenic nutrients (high fat or lysine/leucine


Describe the metabolism of pyruvate (various pathways) including cofactors involved.

Pyruvate to alanine by alanine aminotransferase (ALT) (B6)

Pyruvate to oxaloacetate by pyruvate decarboxylase (B7)

Pyruvate to acetyl coa by Pyruvate dehydrogenase (B1-5, lipoic acid)

Lactic acid dehydrogenase (B3): end of anaerobic glycolysis


What are the symptoms of G6PD? What can cause outbreaks? Inheritance? What lab findings are there?

No NADPH means RBCs can't detoxify free radicals leading to hemolytic anemia upon exposure to oxidizing agents

Fava beans, sulfonamides, primaquine, antituberculosis drugs, infection

X linked recessive

Heinz bondies (denatured Hb)
Bite cells (phagocytic removal of heinz bodies)


What is the pathophys of essential fructosuria? Symptoms?

Fructokinase (fructose to fructose 1 phosphate)

fructose in blood and urine, benign


What is the pathophys of fructose intolerance? Symptoms? Lab Findings? treatment?

No Aldolase B (fructose 1-P to DHAP and Glyceraldehyde) results in increased F1P leading to decreased phosphate leading to decreased glycogenolysis and gluconeogenesis.

Urine dipstick tests negative for glucose but a reducing sugar is found.

Hypoglycemia, jaundice, cirrhosis, vomiting

Decr. intake of fructose and sucrose


What is the pathophys of galactokinase deficiency? Symptoms?

No galactokinase--->galactitol

Galactose in blood and urine
Infantile cataracts
failure to track objects or develop a social smile


What is the pathophys of classic galactosemia? Symptoms? Lab Findings? treatment?

galactosee 1 phosphate uridyltransferase. Damage caused by accumulation of toxic substances (galactitol=lens of eye)

failure to thrive, jaundice, hepatomegaly, infantile cataracts, intell. disability, e. coli sepsis

exclude galactose and lactose

Fructose-Aldolase B


What does sorbitol dehydrogenase do? What cells don't have it and only have aldose reductase? What does aldose reductase do? What is the result in these cells?

Glucose to sorbitol (aldose reductase) to fructose (sorbitol dehydrog)

Schwann cells, retina, lens, and kidneys don't have sorb. dehydr. which leads to build up of sorbitol (diabetic complications in these organs)


What is the pathophys of lactase defic. both primary and secondary disease? Lab findings? Treatment?

lack of lactase enzyme leads to dietary lactose intolerance.

Primary: age dependent

Secondary: loss of brush border due to gastroenteritis, etc.

Bloating, cramps, flatulence, diarrhea

Stool demonstrates decrease pH and breath shows incr. hydrogen content with lactose tolerance test. Normal intestinal mucosa

Avoid diary products or add lactase pills.


What is the purpose of the the urea cycle. Describe its basic steps. Structure of urea.

To get rid of excess NH3.

CO2 and NH3 are converted to carb. phosphate by CPSI using Nag.

Ornithine is combined with carb. phosph. by ornithine transcarbamylase to citrulline.

A cycle ensues and when ornithine is reformed, urea is released and sent to the kidney.

aldehyde bound to two NH2 groups


Describe the cori cycle and the cahill cycle.


In muscle, amino acids (NH3) are converted to alpha ketoacids while alpha ketoglutarate is converted to glutamate (NH3)

Then pyruvate is converted to alanine (NH3) while glutamate (NH3) is conv. to alpha keto.

Alanine is transferred in the blood to the liver, where it is converted back into pyruvate (using) alpha keto. and glut.

Pyruvate is conv. to glucose then transferred in the blood back to muscle, where it is conv. to pyruvate.

In the liver, glut undergoes the urea cycle to form urea with the NH3


Similar to cahill, but pyruvate is conv. to lactate in muscle

Lactate is then transferred to the liver, where it is conv. to pyruvate then glucose, which is transferred back to muscle.


What are the symptoms of ammonia intoxification? What is the pathophys? What is the treatment?

Tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, and blurring of vision

Acquired or hereditary. Excess NH4 depletes alpha ketoglutarate leading to inhibition of TCA

Limit protein in diet. Lactulose to acidfy the GI tract and trap NH4 for excretion. Rifaximin to decr. colonic ammoniagenic bacteria. Benzoate or phenylbutyrate (bind amino acid leading to excretion)


What is the pathophys of n-acetylglutamate synthase deficiency? How does it present? What else presents this way?

NAG is a required cofactor for CPSI. If the synthase isn't present it leads to hyperammonemia

It presents in neonates as poorly regulated resp. and body temp, poor feeding, devel. delay, intell. disab.

Identical to CPS-I deficiency


What is the inher. of ornithine transcarbamylase deficiency? Of the other urea cycle enzyme defic? When does it present? What is the pathophys? What are the findings?

X-linked recess (others autos. recessive)

First few days of life, maybe later

No urea cycle-can't eliminate NH3, build up of CP which is converted to orotic acid

Incr. orotic acid in blood and urine, decr. BUN, symptoms of hyperammonemia, No megaloblastic anemia (vs. orotic aciduria)


What are the steps in catecholamine synth/tyrosine catab? Which enzymes are involved? Which illnesses can occur at the different steps? What cofactors are necessary?

Phenylalanine to tyrosine (phenyl hydroxylase) (BH4) (PKU)

Tyrosine to Homogentisic acid to maleylacetoacetic acid (homogentisate oxidase) (alkaptonuria) to fumarate to TCA cycle

Tyrosine to DOPA (tyrosine hydroxylase) (BH4)

DOPA to melanin (Tyrosinase (albinism))

DOPA to Dopamine (DOPA decarboxylase) (B6)

Dopamine to NE (vitamin C)

NE to Epi (PNMT) (SAM)


What is the pathophys of phenylketonuria? What are the findings? Treatment? What is the pathophys of maternal PKU? Findings?

Decr. phenylalanine hydroxylase or decr. BH4 makes tyrosine essential and leads to a build up of phenyalanine (phenylketones in urine)

Intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor

Decr. Phenyl. and incr. tyrosine in diet, BH4 supplementation (avoid aspartame)

Maternal PKU-lack of control during pregnancy: Microcephaly, intell. disability, growth retard, and cong. heart defects


What is the pathophys of maple syrup urine disease? Findings? Treatment? Inheritance

I Love Vermont maple syrup from maple trees (with branches)

blocked degradation of branched amino acids (Isoleucine, leucine, and valine) due to decr. alpha ketoacid dehydrogenase (B1).

Severe CNS defects, intellectual disability, and death
Maple syrup urine
Incr. alpha ketoacids in blood

Restriction of ILV + thiamine supplementation

Auto Recess.


What is the pathophys of alkaptonuria? Symptoms?

Deficiency of Homogentisate oxidase in the degradative pathway of tyrosine to fumarate leads to pigment forming homogentisic acid in tissue.

Usually benign
dark CT, brown sclerae, urine turns black on prolonged exposure to air. May have debilitating arthralgias


What are the steps (enzymes) in the conv. of methionine to cysteine? What are the pathophys of the different types of homocystinuria? Findings?

Methionine to homocysteine (Homocysteine methyltransferase (B12)) to cystathionine (cystathionine synthase (B6)) to cysteine

They basically are deficiencies of the different enzymes involved in this process
They all result in excess homocysteine

Incr. homocysteine in urine, intell. disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation, thrombosis, and atherosclerosis


What is the pathophys of cystinuria? Symptoms? Treatment? Diagnosis?

Defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of COLA (cysteine, ornithine, lysine, and arginine)

Hexagonal cystine (2 cysteines with disulfide bond) kidney stones

Urinary alkalinazation and chelation agents,
Good hydration (incr. solubility of stones)

Urinary cyanide Nitroprusside test


Describe glycogen regulation y insulin and glucagon/epi.

Epinephrine at beta receptor (liver and muscle) and glucagon at glucagon receptor activate adenylate cyclase which increases cAMP which increases protein kinase A.

Epinephrine at alpha receptor (liver) results in an increase in calcium from the SER which binds to calmodulin.

calcium-calmodulin, calcium, and protein kinase A all activate glycogen phosphorylase kinase which activates glycogen phosphorylase which converts glycogen to glucose

Protein kinase A inhibits glycogen synthase

Insulin receptor (liver and muscle) (tyrosin kinase) activates glycogen synthase and protein phosphatase

Protein phosphatase activates glycogen synthase and inhibits glycogen phosphorylase.


Describe the step (enzymes) involved in glycogenolysis and glycogen synth

Glucose 6P to glucose 1P to UDP glucose to glycogen (glycogen synthase). Branches added by branching enzyme.

Glucose residue removed by glycogen phosphorylase. At 4 residues to a branch, debranching enzyme takes of 3 and adds them to the non branched segment. Then another debranching enzyme takes of the final branched residue.


What are glycogen storage diseases? What are types I, II, III, and V?

Abnormal glycogen metabolism leading to an accumulation of glycogen within cells.

Very Poor Carb Metabolism

Von Gierkes


What is the deficient enzyme in Von Gierkes? The findings? Treatment? Enzyme deficient in pompe? findings? Enzyme deficient in cori? Findings? Enzyme deficient in mccardle? Findings? Treatment?


Glucose 6 phosphatase

Severe fasting hypoglycemia
increased glycogen in liver
increased blood lactate
increased TGs
Incr. uric acid

Oral glucose/cornstarch; avoidance of fructose and galactose


Lysosomal alpha 1,4 glucosidase (acid maltase)

hypertrophic cardiomyopathy
exercise intolerance
systemic findings leading to early death


debranching enzyme

milder for of type 1 with normal blood lactate levels


skel. muscle glycogen phosphorylase

incr. glycogen in muscle that muscle can't break down leading to painful muscle cramps
myoglobinuria with strenuous exercise
arrhythmia from electrolyte abnormalities

Treat with vit. B6


List the substrates, products, and enzymes involved in sphingolipid metabolism as well as the LSDs involved in those steps. Findings in the diseases.

GM2 to GM3 (hexoaminidase A)=Tay Sachs=progressive neurodegeneration, devel. delay, cherry red macula, lysosomes with onion skin, no hepatosplenomegaly. Thai person with a red sac on his head (neuro) full of onions. The sac keeps dropping onions (degeneration) so they end up being delayed. They're holding a hexagonal shield with GM2 written on it to protect their gut (no HSM/hexoaminidase)

GM3 to glucocerebroside

Ceramide trihexoside to glucocerebroside(alpha galactosidase A)=Fabry=peripheral neuropathy of hands and feet, angiokeratomas, and CV/renal disease (Fab Bri=Brian travels the world following rivers (CV/Renal) and jumping from rock to rock (angiokeratomas) and reaching the end of the earth (peripheral neuro) until he leaves the earth (galactosidase A). If he ever gets tired he drinks from his ceramic flask (ceramide trihexoside)

Glucocerebroside to ceramide (glucocerebrosidase)=Gaucher=HSM, pancytopenia, osteoporosis, aseptic necrosis of the femur, bone crises, gaucher cells (lipid laden macrophages that look like crumpled tissue paper. Treatment is recombinant glucocerebrosidase. (Gaucho bull fighter with his crumpled tissue paper flag that doesn't work very well so he gets hit by the bull a lot. The bull gores him in the gut (HSM) then stomps on him breaking all his bones leaving him there bleeding (pancytopenia)). When the damage is done, the fans pour sugar onto his brain (glucocerebroside)

Sulfatides to Galactocerebroside (Arylsulfatase A)=Metachromatic leukodystrophy=central and peripheral demyelination with ataxia, dementia (You walk down a street with beautiful colored homes then eventually arrive to 3 houses that are still a mustard yellow (arylsulfatase/sulfatides)

Galactocerebroside to Ceramide (Galactocerbrosidase)=Krabbe=peripheral neuropathy, developmental delay, optic atrophy, and globoid cells. (A crab is running through endless tunnels to get to the end of the earth. However, since he can barely see the globe he's carrying due to the fact that his huge eyes aren't working, he is quite delayed.

Sphingomyelin to Ceramide (sphingomyelinase)=Niemann-Pick=progressive neurodegeneration, HSM, foam cells (lipid laden macrophages), cherry red spot. (No man picks his nose with his sphinger=a Ute at an Aggie's game is using a huge red foam finger to pick his nose. He goes to far and causes a red spot in his eye. He then continues and progressively damages his brain. The aggie's bull comes and gores him in the gut (HSM)


What are the two mucopolysaccharidoses? What enzyme is deficient? Accumulated substance? Findings?

Hurler Syndrome=alpha iduronidase=heparan sulfate and dermatan sulfate=developmental delay, gargoylism, airway obstruction, corneal clouding, and hepatosplenomegaly. (A huge Idol (iduronidase) comes alive and is walking (-ase not -ate, it is active). However, gargoyles start to climb on it and slow it down (delay). They are hitting its eyes, jumping into its mouth, and a horned bull gargoyle gores it in the gut (HSM).)

Hunter syndrome=Iduronate sulfatase=heperan sulfate and dermatan sulfate=mild hurler plus aggressive behavior, no corneal clouding. (The same idol gets really mad and aggressive (behavior) with these gargoyles and swipes them off his eyes entirely (no corneal clouding) and starts to swipe them off the rest of his body. Because of his aggression, a hunter shows up and starts shooting the X (xlinked) on his chest, essentially stopping him in his tracks (-ate not -ase).


What are the two shuttles involved in FA metabolism? What are the basic steps in each?

Citrate shuttle moves citrate from the mitochondrial matrix into the cell cytoplasm at which point it can be converted to acetyl CoA then to malonyl coa then to fatty acids.

In the cytoplasm, fatty acid is combined with CoA then shuttled into the mitochondrial matrix using the carnitine shuttle then broken down into acyl coa (Beta hydroxylation) which can be used in the TCA cycle or to make ketone bodies.



What is the pathophys of systemic primary carnitine deficiency? The findings?

No transport of LCFAs into mitoch leading to toxic accumulation.

Weakness, hypotonia, hypoketotic hypoglycemia


What is the pathogenesis of MCAD deficiency? Presentation/findings?

Inability to break down FAs into acetyl coa leading to accumulation of 8-10 carbon fatty acyl carnitines in the blood.

Hypoketotic hypoglycemia
In infancy or early childhood with vomiting, lethargy, seizures, coma, and liver dysfunction.
Minor illness can lead to sudden death.
No fasting.


What are the ketone bodies? Where and what from are they created? What are the steps in their creation? What causes them to be created?

Acetoacetate and beta hydroxybutyrate

In liver, FAs and AAs are metabolized to them.

Breath smells like acetone (only acetoacetate found in urine)

In starvation and DKA, oxaloacetate is depleted for gluconeogenesis so acetyl Coa can't enter TCA cycle.

In alcoholism, oxaloacetate is shunted to malate due to excess NADH so acetyl coa can't enter TCA cycle.

The acetyl coa can thus only be used for ketone bodies

Acetyl coa to acetoacetyl coa to HmG CoA to Acetoacetate to beta hydroxybutyrate.


How much time during exercise does it take for stored ATP, Creatine phosphate, anaerobic metabolism, and aerobic metabolism t be used up>

ATP=2 sec.
Creatinine=10 sec.
Anaerobic=1 min.
Aerobic=2 hours and onwards.


What are the priorities during fasting and starvation? How is energy produced during a fed state? Fasting (between meals)? 1-3 days? after 3 days? Hormones involved in each step?

Supply glucose to the brain and RBCs and preserve protein.

glycolysis and aerobic respiration
Insulin stimulates storage of lipids, proteins and glycogen

Hepatic glycogenolysis (major); hepatic gluconeogenesis, adipose release of FFA (minor)
Glucagon and epinephrine stimulate use of fuel reserves

1-3 DAYS
Blood glucose maintained by:
Hepatic glycogenolysis
adipose release of FFA
muscle and liver, which shift fuel use from glucose to FFA
Hepatic gluconeogenesis from peripheral lactate and alanine and from adipose tissue glycerol and propionyl coA
Glycogen reserves depleted after 1 day
RBCs lack mitochondria and therefore cannot use ketones

Adipose stores (ketone bodies become the main source of energy for the brain). After these are depleted, vital protein degradation accelerates leading to organ failure and death
Amount of excess stores determines survival time.


What is the function of cholesterol? What is the rate limiting step of cholesterol synth? How is that modulated? What does it do? What is LCAT and what does it do? How do statins work?

Maintain cell membrane integrity and synthesize bile acid, steroids, and vitamin D

Rate limiting step (HMG-CoA to mevalonate) is catalyzed byHMG-CoA reductase (induced by insulin)

LCAT (Lecithin cholesterol acyltransferase esterifies 2/3 of plasma cholesterol


Describe the process of lipid transport basically including the enzymes involved.

Fats are eaten.

pancreatic lipase degrades TG in small intestine. They enter into chylomicrons. Chylomicrons are released into circulation via lymph system.

Lipoprotein lipase degrades TGs circulating in chylomicrons and VLDLs. Found on vascular endothelial surface.

Chylomicron remnants bind to remnant receptors on the liver and deliver cholesterol to liver.

VLDL is released from the liver, LPL releases FFAs to peripheral tissues, which converts VLDL to IDL.

IDL binds to LDL receptors in the liver

Also, Hepatic TG lipase (in periphery) degrades the remaining TGs, thus converting IDL to LDL

LDL delivers hepatic cholesterol to peripheral tissues. It is taken up by LDL receptors in peripheral tissues and the liver via endocytosis.

HDL transports cholesterol from the periphery to the liver.

Hormone sensitive lipase degrades TGs stored in adipocytes releasing them into circulation.


What is the function of HDL? Where is it created? What enzymes are involved in its development?

HDL is produced in the liver and the intestine in its nascent form. LCAT catalyzes esterification of cholesterol in HDL. Then Cholesterol ester transfer protein (CETP) transfers to esters to other lipoproteins.


Where are the different apolipoproteins located and what are their functions?

E=mediates remnant uptake=found in all lipoproteins

A-I=activates LCAT=Found in chylomicrons and HDL

C-II=lipoprotein lipase cofactor=found in chylomicrons, VLDL, and HDL

B-48=mediates chylomicron secretion=found in chylomicrons and their remnants

B-100=binds LDL receptor. Found in VLDL, IDL, and LDL.


What is increased in the blood in type I, IIa, and IV familial dyslipidemias? What is a different name for each? What is the pathophys/genetics of each? Symptoms of each?


chylomicrons, TG, and cholesterol increased.

Autosomal recessive

LPL deficiency or altered C-II.

Pancreatitis, HSM, eruptive/pruritic xanthomas (no incr. risk of atherosclerosis). Creamy layer in supernatant.


LDL, cholesterol increased

Auto dominant

Absent or defective LDL receptors.

Heterozygotes have chol.=300 mg/dL.
Homozygotes have chol.=700+. Accelerated atherosclerosis (MI before 20), tendon (Achilles) xanthomas, corneal arcus


VLDL, TG incr.

auto dominant

Hepatic overproduction of VLDL

Hypertriglyceridemia (>1000 mg/dL) can cause acute pancreatitis.