Biochemistry 7

Front 1

Fabry disease

Back 1

Cause: alpha-galactosidase A deficiency -> accumulation of ceramide trihexoside.

Inh: X-linked recessive

Symp: peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease.

Front 2

Gaucher disease

Back 2

Most common sphingolipidosis. AR.

Cause: Glucocerebrosidase (beta-glucosidase) deficiency -> accumulation of glucocerebroside.

Symp: Hepatosplenomegaly, pancytopenia,
aseptic necrosis of femur, bone crises, Gaucher cells A (lipid laden macrophages resembling
crumpled tissue paper).

Treat: recombinant glucocerebrosidase.

Front 3

Niemann-Pick disease

Back 3

Cause: sphingomyelinase deficiency -> accumulation of sphingomyelin. AR.

Symp: Progressive neurodegeneration, hepatosplenomegaly, “cherry-red” spot on macula, foam cells (lipid laden macrophages)

Front 4

Tay-Sachs

Back 4

Cause: Hexominidase A deficiency -> G2 ganglioside accumulation. AR.

Symp: progressive neurodegeneration, developmental delay, lysosomes with onion skin, cherry red spot on macula, no hepatosplenomegaly

Front 5

Krabbe disease

Back 5

Cause: Galactocerebrosidase deficiency -> galactocerebroside accumulation. AR.

Symp: Peripheral neuropathy, developmental
delay, optic atrophy, globoid cells

Front 6

Metachromatic leukodystrophy

Back 6

Cause: Arylsulfatase A deficiency -> cerebroside sulfate accumulation. AR.

Symp: Central and peripheral demyelination
with ataxia, dementia

Front 7

Hurler syndrome

Back 7

Cause: alpha-L-iduronidase deficiency -> heparan sulfate, dermatan sulfate accumulation. AR.

Symp: gargoylism, developmental delay, corneal clouding, airway obstruction, hepatosplenomegaly

Front 8

Hunter syndrome

Back 8

Cause: Iduronate sulfatase deficiency -> heparan sulfate, dermatan sulfate accumulation. XR.

Symp: mild Hurler+aggressive behavior, no corneal clouding

Front 9

What shingolipidoses are more common among Ashkenazi jews?

Back 9

Tay-Sachs, Niemann-Pick, some forms of Gaucher disease.

Front 10

What is lipoprotein lipase and where it can be found?

Back 10

Enzyme that degrades TG circulating in chylomicrons and VLDLs. Found on vascular endothelial surface

Front 11

Draw circulation pathways of dietary fat and cholesterol

Back 11

Front 12

What does hormone-sensitive lipase do?

Back 12

Degrades TG stored in adipocytes

Front 13

What is LCAT?

Back 13

Lecithin-cholesterol acyltransferase. It catalyzes esterification of 2/3 of plasma cholesterol

Front 14

Statins mechanism of action

Back 14

Competitively and reversibly inhibit HMG-CoA reductase

Front 15

What is CETP?

Back 15

Cholesterol ester transfer protein, mediates transfer of cholesterol esters to other lipoprotein particles.

Front 16

Regulation of HMG-CoA reductase

Back 16

Insulin (+)

Front 17

Where does energy (ATP) come from after a meal?

Back 17

Glycolysis and aerobic respiration

Front 18

What hormone is active after a meal and what processes does it contribute to?

Back 18

Insulin. Stimulates storage of lipids, glycogen, proteins.

Front 19

Where does energy come from between meals (fasting state)?

Back 19

Glycogenolysis (major); hepatic gluconeogenesis, release of FFA from adipose tissue (minor).

Front 20

What hormones are active in a fasting state and what processes do they contribute to?

Back 20

Glucagon and epinephrine stimulate use of fuel reserves.

Front 21

How blood glucose level is maintained in 1-3 days of starvation?

Back 21

Hepatic glycogenolysis; adipose release of FFA; liver and muscle start to use FFA to save glucose; hepatic gluconeogenesis from peripheral alanine and lactate, from adipose tissue glycerol and propionyl-CoA.

Front 22

What TG components can contribute to gluconeogenesis?

Back 22

Odd chain fatty acids -> propionyl-CoA -> succinyl-CoA

Front 23

How fast glycogen reserves deplete?

Back 23

After day 1 of starvation

Front 24

What conditions can lead to overproduction of ketone bodies and why?

Back 24

In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis. In alcoholism, excess NADH shunts oxaloacetate to malate. Both processes cause a buildup of acetyl-CoA, which shunts glucose and FFA toward the production of ketone bodies.

Front 25

What is the source of energy for organism after day 3 of starvation?

Back 25

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.

Front 26

Carnitine deficiency

Back 26

Inability to transport LCFAs into the mitochondria, resulting in toxic accumulation. Causes weakness, hypotonia, and hypoketotic hypoglycemia.

Front 27

What fruity odor of breath indicates to?

Back 27

Fruity odor, or acetone odor, of the breath indicates to high level of ketone bodies.

Front 28

Draw FA synthesis pathway

Back 28

Front 29

Draw FA degradation pathway

Back 29

Front 30

FA oxidation regulation

Back 30

Rate-limiting enzyme is carnitine acyltransferase I, (-) by malonyl-CoA

Front 31

FA synthesis regulation

Back 31

Rate-limiting enzyme is acetyl-CoA carboxylase, (+) by insulin, citrate; (-) glucagon, palmitoyl-CoA.

Front 32

Cholesterol synthesis regulation

Back 32

Rate-limiting enzyme is HMG-CoA reductase, (+) insulin, thyroxine, (-) by cholesterol, glucagon.

Front 33

Von Gierke disease

Back 33

Glycogen storage disease type I. Glucose-6-phosphatase deficiency. AR. Symp: severe fasting hypoglycemia, ↑↑ glycogen in liver, ↑ blood lactate, hepatomegaly. Treatment: frequent oral glucose/cornstarch; avoidance of fructose and galactose.

Front 34

Pompe disease

Back 34

Glycogen storage disease type II. Lysosomal alpha-1,4-glucosidase (acid maltase) defificency. AR. Symp: Cardiomyopathy and systemic findings leading to early death.

Front 35

Cori disease

Back 35

Glycogen storage disease type III. Debranching enzyme alpha-1,6-glucosidase deficiency. AR. Milder form of type I with normal blood lactate levels. Gluconeogenesis is intact.

Front 36

McArdle disease

Back 36

Glycogen storage disease type V. Skeletal muscle glycogen phosphorylase (myophosphorylase) deficiency. AR. Symp: ↑ glycogen in muscle, but cannot break it down, leading to painful muscle cramps, myoglobinuria (red urine) with strenuous exercise, and arrhythmia from electrolyte abnormalities.

Front 37

Symptoms of ammonia intoxication

Back 37

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

Front 38

Causes of hyperammonemia

Back 38

Can be acquired (e.g., liver disease) or hereditary (e.g., urea cycle enzyme deficiencies).

Front 39

Treatment of hyperammonemia

Back 39

Limit protein in diet. Benzoate or phenylbutyrate (both of which bind amino acid and lead to excretion) may be given to ↓ ammonia levels. Lactulose to acidify the GI tract and trap NH4+ for excretion.

Front 40

How can excess amount of NH4+

Back 40

Excess NH4+ depletes alpha-KG, leading to inhibition of TCA cycle.

Front 41

N-acetylglutamate deficiency

Back 41

Required cofactor for carbamoyl phosphate synthetase I. Absence of N-acetylglutamate → hyperammonemia. Presentation is identical to carbamoyl phosphate synthetase I deficiency. However, ↑ ornithine with normal urea cycle enzymes suggests hereditary N-acetylglutamate deficiency.

Front 42

Draw urea cycle

Back 42

Front 43

Draw transport of ammonia by glutamate and alanine

Back 43

Front 44

What is the most common urea cycle disorder?

Back 44

Ornithine transcarbamylase deficiency

Front 45

What happens to excess carbamoyl phosphate in OTC deficiency?

Back 45

It is converted to orotic acid (part of pyrimidine synthesis pathway

Front 46

OTC deficiency, findings

Back 46

↑ orotic acid in blood and urine, ↓ BUN, symptoms of hyperammonemia. No megaloblastic anemia (vs. orotic aciduria). Often evident in the first few days of life, but may present with late onset. XR.

Front 47

Cause of cystinuria, mode of inheritance, epidemiology.

Back 47

Hereditary defect of renal PCT and intestinal amino acid for Cysteine, Ornithine, Lysine, and Arginine (COLA). Excess cystine in the urine can lead to precipitation of hexagonal cystine stones. AR. Common (1:7000).

Front 48

Cistinuria treatment

Back 48

Urinary alkalinization (e.g., potassium citrate, acetazolamide) and chelating agents ↑solubility of cystine stones; good hydration.

Front 49

How diagnosis of cistinuria is confirmed?

Back 49

Positive urinary cyanide-nitroprusside test (the addition of fresh sodium cyanide formed by sodium nitroprusside to a sample of urine gives rise to a stable red-purple color in the presence of cystine).

Front 50

Different types of homocystinuria and appropriate treatment

Back 50

(1) Cystathionine synthase deficiency (treatment: ↓ methionine, ↑ cysteine, ↑ B12 and folate in diet);

(2) ↓affinity of cystathionine synthase for pyridoxal phosphate (treatment: ↑↑ B6 and ↑ cysteine in diet);
(3) Homocysteine methyltransferase (methionine synthase) deficiency (treatment: ↑ methionine in diet).

Front 51

Homocystinuria findings

Back 51

↑↑ homocysteine in urine, intellectual disability, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), thrombosis, and atherosclerosis (stroke and MI)

Front 52

Draw homocysteine metabolism

Back 52

Front 53

What phenylketones do you know?

Back 53

Phenylacetate, phenyllactate, phenylpyruvate

Front 54

PKU symptoms

Back 54

Intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor. Tyrosine becomes essential. Excess phenylketones in urine. Screened for 2-3 days after birth (normal at birth because of maternal enzyme during fetal life)

Front 55

PKU treatment

Back 55

↓Phe, ↑Tyr in diet. Avoid the artificial sweetener aspartame, which contains Phe

Front 56

Maternal PKU

Back 56

Develops as a result of a lack of proper dietary therapy during pregnancy in women with PKU. Findings in infant: microcephaly, intellectual disability, growth retardation, congenital heart defects

Front 57

Causes of PKU

Back 57

(1) phenylalanine hydroxylase deficiency, (2) tetrahydrobiopterin deficiency (malignant PKU). AR. Incidence 1:10,000.

Front 58

Alkaptonuria cause

Back 58

Homogentisate oxidase deficiency. AR.

Front 59

Alkaptonuria findings

Back 59

Benign disease. Dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid is toxic to cartilage).

Front 60

What is the structure of cystine?

Back 60

It is made of two cysteines connected by a disulfide bond.

Front 61

Maple syrup urine disease, cause and symptoms

Back 61

Blocked degradation of branched aminoacids (Isoleucine, Leucine, Valine) due to ↓α-ketoacid dehydrogenase (B1). Causes ↑α-ketoacids in the blood, especially those of leucine. Causes severe CNS defects, intellectual disability, and death. AR. Urine smells like maple syrup/burnt sugar.

Front 62

Maple syrup urine disease treatment

Back 62

Restriction of leucine, isoleucine, and valine in diet, and thiamine supplementation.

Front 63

Phe derivates

Back 63

Front 64

Trp derivates

Back 64

Front 65

His derivates

Back 65

Front 66

Glutamate derivates

Back 66

Front 67

Glycine derivates

Back 67

Front 68

Arginine derivates

Back 68