Biochem

Question 1

4 day old, abnormal movements, tonic posturing (intermittent), increased mmuscle tone, poor feeding, vomiting, irritability. Diapers smell like caramelizing sugar.
Diagnosis?
supplementation?

Answer 1

Maple syrup urine disease

high dose thiamine

Question 2

an autosomal recessive disorder characterized by defective breakdown of branched-chain amino acids (leucine, isoleucine, and valine) degradation of these amino acids make them alpha ketoacids which are then metabolized by branched chain alpha ketoacid dehydrogenase complex (BCKDC)

mutations in BCKDC result in accumulation of branched- chain amino acids in serum and peripheral tisses causinf neurotoxicity and causing the sweet odor in urine

Answer 2

Maple syrup urine disease

Question 3

branched chain alpha ketoacid dehydrogenase requires 5 cofactors what are they?

Answer 3

thiamine, lipoate, coenzyme A, FAN, NAD

Tender Loving Care For Nancy

Question 4

most disorders of the urea cycle require _______ as an essential amino acid

Answer 4

arginine

helps produce downstream water soluble intermediates that lead to nitrogen disposal and decreased plasma ammonia levels

Question 5

Cobalamine (B12) deficiencies lead to

Answer 5

megaloblastic anemia, neurologic changes including peripheral neuropathy and elevated plasma levels of homocysteine (a prothrombic substance)

Question 6

tetrahydrobiopterin deficiency results in _____

Answer 6

phenylketonuria

Question 7

________disease (glucose-6-phosphatase deficiency) typically have hepatomegaly, hypoglycemia, seizures, and/or lactic acidosis

Answer 7

von gierke disease

Question 8

______ disease (lysosomal α-1,4-glucosidase deficiency) classically causes cardiomegaly and severe hypotonia.

Answer 8

pompe disease

Question 9

_____ disease (globotriaosylceramide accumulation) causes angiokeratomas, peripheral neuropathy, and glomerulopathy that typically present in adulthood.

Answer 9

fabry disease

Question 10

______disease (galactocerebroside accumulation) causes progressive neurodegeneration. However, patients with this disease also have peripheral neuropathy and optic atrophy.

Answer 10

krabbe disease

Question 11

______ disease is an autosomal recessive disorder caused by β-hexosaminidase A deficiency, which results in GM2 ganglioside accumulation. Key clinical features include progressive neurodegeneration and a cherry-red macular spot. In contrast to patients with ______ disease, those with this disease have no hepatosplenomegaly.

Answer 11

tay- sachs

niemman pick

Question 12

Hepatomegaly occurs in several lysosomal storage diseases. In ________ disease, an accumulation of sphingomyelin also causes progressive neurodegeneration and cherry-red macular spots. In _______ and ___syndromes, accumulation of heparan and dermatan sulfate results in developmental delay, skeletal abnormalities, and cardiac disease.

Answer 12

Neimann-Pick

hunter and hurler

Question 13

α-galactosidase A (used for breakdown of Gb3) deficiency causes accumulation of the sphingolipid globotriaosylceramide. The earliest manifestations of _______ are neuropathic pain and angiokeratomas. Glomerular (eg, proteinuria, renal failure), cardiac (eg, left ventricular hypertrophy), and cerebrovascular (eg, transient ischemic attack, stroke) complications develop in adulthood.

progressive skin rash/
intermittent burning sensation in his palms and soles that is exacerbated by stress and fatigue/
burning sensation is particularly severe after exercise, during which the patient notes that he sweats minimally. Skin examination shows clusters of non-blanching, red papules in the gluteal, inguinal, and umbilical areas

Answer 13

Fabry disease

X-linked recessive

Question 14

Cystinuria is due to impaired transport of renal cystine (a homodimer of cysteine), which leads to cystine renal stone formation. Clinical manifestations typically include

Answer 14

flank pain, hematuria, and possible stone passage in children or adolescents.

Question 15

_________ results from an inability to convert phenylalanine to tyrosine by the phenylalanine hydroxylase system, making ______ an essential amino acid in these patients. Classic clinical features of untreated PKU include intellectual disability, seizures, light pigmentation, and a “musty” odor.

the excess phenylalanine inhibits tyrosinase, which normally results in the downstream production of melanin. The lack of melanin causes the fair complexion seen in this patient.

Answer 15

phenylketonuria

tyrosine

Question 16

_______ use by the body is maximal in states of accelerated carbohydrate metabolism because thiamine acts as a cofactor for the enzymes transketolase (pentose phosphate pathway), α-ketoglutarate dehydrogenase (TCA cycle), and pyruvate dehydrogenase (forms acetyl-CoA).

Answer 16

​​​​​​​thiamine

Question 17

is a fat-soluble vitamin that functions as a scavenger of free radicals (antioxidant). Deficiency of vitamin E is rare but can result in neurologic dysfunction (ataxia, hyporeflexia, loss of sensation) as well as hemolytic anemia.

Answer 17

tocopherol (vit E)

Question 18

The co enzymes ____ and ____ form the prosthetic groups of several enzymes important in electron transport; both are synthesized from riboflavin (vitamin B2). Clinical features of deficiency include sore throat, stomatitis, glossitis, normocytic anemia, and seborrheic dermatitis.

Answer 18

The coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)

Question 19

________ acts as a coenzyme in the decarboxylation and transamination of amino acids, including the metabolism of tryptophan to niacin. Deficiency of pyridoxine leads to anemia, peripheral neuropathy, and dermatitis.

Answer 19

Pyridoxine (vit B6)

Question 20

is a water-soluble vitamin required for hydroxylation of proline and lysine residues during collagen synthesis. Deficiency results in

Answer 20

Ascorbate (vit C)

scurvy, a disease characterized by bone pain, easy bruising, and poor wound healing.

Question 21

______ is an essential amino acid and a precursor for niacin, serotonin, and melatonin.

Answer 21

tryptophan

Question 22

is caused by impaired transport an autosomal recessive metabolic disorder, causing mutationss affecting the neutral amino acid trasporterin the small intestine (loose stools)and proximal tubule of the kidney (resulting in impoared transport of neutral amino acids mainly tryptophan). Symptoms include pellagra-like skin eruptions (pruritic skin rash in sun exposed areas) and cerebellar ataxia (gait instability), which occur as a result of ______deficiency. The diagnosis can be confirmed through detection of excessive amounts of neutral amino acids in the urine.

Answer 22

Hartnup disease

niacin

Nuetral AA
(alanine, serine, threonine, valine, leucine, isoleucine, phenylalanine, tyrosine, and tryptophan)

A high-protein diet along with daily niacin or nicotinamide supplementation generally results in significant symptom improvement.

Question 23

______ required for the synthesis of catecholamines is obtained from either dietary intake or by conversion of phenylalanine by phenylalanine hydroxylase in the liver.

deficiency of _____ hydroxylase impairs catcholamine synthesis and causes ______ and _____

Answer 23

tyrosine

infantile parkinsonism and progressive encephalopathy.

Question 24

Catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) are responsible for

Answer 24

the inactiavtion of catecholamines

COMT converts epinephrine to metanephrine and norepinephrine to normetanephrine; MAO converts metanephrine and normetanephrine to vanillylmandelic acid.

Question 25

The 3 main circulating catecholamines are dopamine, norepinephrine, and epinephrine. Norepinephrine and dopamine are produced in the______
epinephrine is produced in the _____

Answer 25

central and peripheral nerbous system

adrenal medulla`

Question 26

Cortisol increases the conversion of norepinephrine to epinephrine in the adrenal medulla by increasing the expression of

Answer 26

phenylethanolamine-N-methyltransferase.

Question 27

_______ are heterotrimeric glycoproteins that bind to type IV collagen underlying epithelial cells. They contribute to the organization and function of the basal lamina (basement membrane).

Answer 27

laminins

Question 28

________ are composed of glycosaminoglycans (GAGs), which provide compressibility to tissues. Patients with deficiencies in lysosomal enzymes cannot break down GAGs, resulting in mucopolysaccharidoses (eg, _____ syndrome, _____ syndrome) characterized by soft tissue and skeletal disease.

Answer 28

proteoglycans

Hurler syndrome, hunter syndrome

Question 29

________ is a major component of the microfibrils that form a sheath around elastin. Microfibrils are abundantly present in blood vessels and in the suspensory ligaments of the lens.

Defects in this component cause classical autosomal dominant ______

Answer 29

Fibrillin-1

Marfan syndrome

Question 30

is another major component of the soft tissue’s extracellular matrix, including synovial fluid and skin. Exogenous injection can be used to restore viscoelasticity to the synovial fluid in osteoarthritis; soft-tissue fillers can also be used in patients concerned about age-related volume loss (eg, nasolabial folds).

Answer 30

Hyaluronic acid

Question 31

______, a fibrous protein in the connective tissue, is named for the elastic properties it imparts to skin, blood vessels, and lung alveoli. _____ fibers can be stretched to several times their original length but will recoil when the stretching forces are withdrawn.

Answer 31

Elastin

Elastin is synthesized from the polypeptide precursor tropoelastin.

Question 32

Collagen types I, II, III, and V provide tensile strength in

Answer 32

skin, bones, cartilage, tendons, and blood vessels.

Question 33

_______is a major component of connective tissue and consists of 3 polypeptide α chains held together by hydrogen bonds to form a ropelike triple helix structure (________). Lysyl oxidase then forms covalent bonds between individual ________ molecules, generating mature _______fibers.

Answer 33

collagen
tropocollagen
tropocollagen
collagen

Collagen types I, II, III, and V provide tensile strength in skin, bones, cartilage, tendons, and blood vessels.

Question 34

is a heritable connective tissue disease associated with abnormal collagen formation. EDS usually manifests clinically as overflexible (hypermobile) joints, overelastic (hyperelastic) skin, and fragile tissue susceptible to bruising, wounding, and hemarthrosis.

Answer 34

Ehlers-Danlos syndrome (EDS)

Question 35

A ________is an upstream promoter region associated with some genes in eukaryotic organisms.______ binding protein binds to this promoter during transcription, unwinding the DNA and initiating separation of the strands.

Answer 35

TATA box

TATA

Question 36

After transcription, eukaryotic pre-mRNA undergoes posttranscriptional modification, which includes the addition of a ______ at the 3’ end and ______ cap at the 5’ end, and the removal of introns.

Answer 36

poly-A tail

methylguanosine

Question 37

AUG and UAG are mRNA

Answer 37

start and stop codons that initiate and terminate translation, respectively.

Question 38

A researcher is studying the expression pattern of a particular gene. Messenger RNA is isolated from several tissues, subjected to electrophoresis, blotted, and probed with radiolabeled DNA containing sequences from exon 4 from that gene. An x-ray film is then placed over the blotting membrane, with the results of the autoradiogram shown below:

what explains the auoradiogram?
what is the name of this study?

Answer 38

Alternate RNA splicing
Northern Blot technique

Alternative splicing is a process where the exons of a gene are reconnected in multiple ways during post-transcriptional processing. This creates different mRNA sequences and subsequently, different protein isoforms. It is a normal phenomenon in eukaryotes that greatly increases the biodiversity of proteins encoded by the genome.

Question 39

is a group of rare hereditary disorders characterized by defective collagen synthesis. It can be caused by procollagen peptidase deficiency, which results in impaired cleavage of terminal propeptides in the extracellular space. Patients often have joint laxity, hyperextensible skin, and tissue fragility due to the formation of soluble collagen that does not properly crosslink.

Answer 39

Ehlers-Danlos syndrome

Question 40

A 2-year-old boy has easy bruising. he develops marked bruising and open wounds following minor trauma.
hyperextensible skin, multiple ecchymoses over the forearms and pretibial regions, and an umbilical hernia.
A skin biopsy is performed, and histochemical evaluation of the biopsy reveals a defect in extracellular processing of collagen.

Diagnosis?
what step of collagen synthesis is most likely impaired?

Answer 40

Ehlers Danlos syndrome

N-terminal propeptide removal

Question 41

Carnitine deficiency impairs fatty acid transport from the _______ into _______, preventing β-oxidation of fatty acids into _______. This leads to cardiac and skeletal myocyte injury (lack of ATP from citric acid cycle) and impaired ketone body production by the liver during fasting periods.

Answer 41

cytoplasm into mtochondria

acetyl CoA

Question 42

________ can be ingested or synthesized from phospholipids in the cell membrane. Its eicosanoid derivatives (eg, prostanoids, leukotrienes) are important modulators of inflammation. It is not affected by carnitine levels.

_________ is a tripeptide that can be synthesized from amino acids (glutamate, cysteine, and glycine). It is an important antioxidant and plays a role in DNA synthesis and repair.

__________ is an amino acid that is synthesized from methionine. Using vitamin cofactors, it can be converted to cysteine (pyridoxine) or recycled into methionine (cobalamin).

_______ is a fatty acid that can be ingested or synthesized from carbohydrates. Palmitate synthesis occurs in the cytosol and would not be affected by carnitine deficiency.

Answer 42

Arachidonic acid

gluthathione

homocysteine

palmitate

Question 43

myopathy (eg, elevated creatine kinase, weakness), cardiomyopathy (eg, S3 gallop), and hypoketotic hypoglycemia (eg, absence of ketones in the urine) in the setting of decreased muscle carnitine content is consistent with?

Answer 43

primary carnitine deficiency

The condition is caused by a defect in the protein responsible for carnitine transport across the mitochondrial membrane. Without sufficient carnitine, fatty acids cannot be transported from the cytoplasm into the mitochondria as acyl-carnitine (carnitine shuttle). The mitochondria therefore cannot β-oxidize the fatty acids into acetyl CoA, the carbon substrate for the citric acid cycle. As a result, cardiac and skeletal myocytes cannot generate ATP from fatty acids (leading to muscle weakness, cardiomyopathy) and the liver is unable to synthesize ketone bodies (manifests as hypoketotic hypoglycemia).

Carnitine deficiency impairs fatty acid transport from the cytoplasm into mitochondria, preventing β-oxidation of fatty acids into acetyl CoA. This leads to cardiac and skeletal myocyte injury (lack of ATP from citric acid cycle) and impaired ketone body production by the liver during fasting periods.

Question 44

A 5-year-old girlseveral months of fatigue and difficulty walking. She ambulates normally at first but rapidly becomes weak and tired. has mild motor delays. mild decreased power in all extremities.
cardiac auscultation shows systolic murmur and an S3 gallop
glucose 37
creatine kinase 304
muscle biopsy shows low carnitine content

diagnosis?
deficient synthesis in what?

Answer 44

acetoacetate

primary carnitate deficiency