M1 Biochem Semester 2 Exam 1

Front 1

What are the basic roles of platelets in blood clotting?

Back 1

Platelets release granules and alter their surface properties. They expose phosphatidylserine on their plasma membrane to assemble the clotting cascade. Platelets aggregate, attach, and spread. They secrete ADP, thromboxane A2, and VWF. Fibrinogen bridges platelets.

Front 2

High yield: How does aspirin act as an anticoagulant?

Back 2

They attack cyclooxygenase which is required for thromboxane synthesis.

Front 3

High yield: What is VWF and in very general terms, what is its function in platelet biology?

Back 3

VMF is a linking protein forms monomers that connect platelets and collagen. Helps with aggregation and formation of multimers.

Front 4

High yield: What does a deficiency in VWF lead to?

Back 4

defective platelet adhesion.
bleeding diathesis
mucosal bleeding

Front 5

High yield:What causes the first step in blood clotting?

What is tissue factor? What is its role in clotting?

Back 5

tissue factor being exposed to plasma

triggers blood clotting when exposed to plasma

Front 6

High yield: What type of enzyme are most blood clotting factors?

Back 6

two-subunit protease with a protein cofactor and serine protease

Front 7

High yield: What is the last protease in the clotting cascade? What does it do?

Back 7

thrombin

Thrombin
converts fibrinogen into fibrin, which spontaneously
polymerizes, or gels. Thrombin is also a potent platelet
activator.

Front 8

High yield: How do coumarin drugs (warfarin) function as anticoagulants?

Back 8

antagonize vitasmin K and depresses dependent carboxylation of clotting factors.

Front 9

High yield: What happens to fibrinogen when the fibrinopeptides are removed? What factor helps make it stronger? what factor helps mediate this process?

Back 9

crosslinks into a clot

Covalent cross-linking by factor XIIIa
stabilizes the fibrin clot.

thrombin

Front 10

In general, how does heparin act as an anticoagulant?

Back 10

accelerating inactivation of Xa
helps with antithrombin

Front 11

High yield: Why is tPA given to patients who present with a myocardial infarction? Can it be given the day after an
MI?
What are side effects?

Back 11

Promote conversion of plasminogen to plasmin which digests fibrin.

No, tissue is dead.

Spontaneous bleeding

Front 12

Which test is used to detect deficiencies in prothrombin, fibrinogen, and factors V, VII and X? Which tests in HK, PK, prothrombin, fibrinogen, factors V, VII, IX, X, and XII?

Back 12

PT and aPTT

Front 13

What triggers trypsinogen to become trypsin and start the cascade of reactions that cleave other zymogens? Where does this happen?

Back 13

enteropeptidase
pancreas

Front 14

What is cystinuria?

Back 14

Inability to absorb cystine in proximal tubule leads to cystine stones in urinary tract

Front 15

What are the 2 methods of removing nitrogen from amino acids?

Back 15

transamination, oxidative deamination

Front 16

What happens during transamination?
What is an example of the enzyme that does this? What is the coenzyme?

Back 16

amino acid + alpha-ketoglutarate --> alpha-ketoacid and glutamate
amino group from the amino acid to the alpha-ketoglutaarate

Aspartate transaminase

B6 or pyridoxyl phosphate

Front 17

What happens in oxidative deamination?

Back 17

Ala + alpha-ketoglutarate --> pyruvate + glutamate
(transfer of amine from amino acid to alpha-ketoglutarate)

glutamate + OAA --> alpha-ketoglutararte + asparate
(opposite)

ATP and GTP
are allosteric inhibitors of glutamate dehydrogenase. ADP and GDP are activators of
the enzyme.

Front 18

How do most muscles transfer ammonia to the liver?
How do muscles?

Back 18

ammonia + glutamate = glutamine (safe for transport)
Liver has glutaminase

Muscle make alanine from pyruvate and glutamate

Front 19

What are the 2 important steps of the urea cycle? Where do they occur?

Back 19

First step occurs in the mitochondria where ammonia and carbon dioxide, both
waste products, are combined using 2 ATPs into carbamoyl phosphate by carbamoyl
phosphate synthetase I in mitochondria. NH3 provides the 1st N.

Arginine is then cleaved to make urea, almost exclusively in the liver

Produced in the liver, excreted in the kidney

Front 20

how do you regulate the urea cycle?

Back 20

NH4 + CO2 --> Carbamoyl phosphate
enzyme: carbamoyl phosphate synthetase I


N-acetylglutamate (NAG) as obligatory allosteric activator of
carbamoyl phosphate synthetase I, in mitochondria. Synthesis of NAG promoted by
glucagon and unaffected by insulin. Also enhanced by arginine, from digestion of
protein-rich meal.

Front 21

What are sources of ammonia?

What are the sources for nitrogen in urea?

Back 21

amino acids, glutamine, bacteria action (urease), amines, purines and pyrimidines

ammonia and aspartate

Front 22

What is the most common transport of ammonia?

How about in muscles, blood, and CNS

muscle only

Back 22

urea

glutamate

alanine

Front 23

What are the symptoms of hyperammonia?

Back 23

a. tremors, slurring of speech, blurring of vision
b. acquired. Cirrhosis from alcoholism, hepatitis, or biliary obstruction may
cause collateral circulation around liver so portal vein shunted into general
circulation, without liver detoxification.
c. Hereditary. Defective enzyme in urea cycle. Within first week of birth.
Mental retardation

Front 24

Why is ammonia toxic?

Back 24

more glutamate is made, depriving the body of the alphaketoglutarates for TCA and brain fuel

ammonia inhibits glutaminase and glutamate is a neurotransmitter

Front 25

How do you treat hyperammonia?

Back 25

limit dietary protein
phenylbutyrate (combines with glutamine to form a substance that comes out in urine)
arginine (activator of urea cycle)

Front 26

What are the sources for the two nitrogens in urea? Where does urea cycle occur?

Back 26

ammonia and aspartate

Front 27

What are the two steps for the removal of amino group from an amino acid? What are the enzymes
mediating these processes? What is the diagnostic value of plasma aminotransferases (AST and ALT)?
How is the activity of glutamate dehydrogenase regulated?

Back 27

1. Transamination: the funneling of amino groups to α-ketoglutarate to make
glutamate. Take an amino acid and a keto acid and exchanges the amino group
Aspartate transaminase is an example of the enzyme that does this. It uses vitamin
B6 or pyridoxyl phosphate as coenzyme.
2. Oxidatively deaminate glutamate to make ammonia. Convert oxaloacetate to
aspartate. The process is mediated by Glutamate dehydrogenase. It regenerates the
α-ketoglutarate but produces ammonia, which enters the urea cycle. ATP and GTP
are allosteric inhibitors of glutamate dehydrogenase. ADP and GDP are activators of
the enzyme.
3. The presence of elevated plasma levels of amintransferases indicates damage to cells
rich in these enzymes since they are intracellular enzymes (ALT and AST).

Front 28

Know the difference between glucogenic and ketogenic amino acids and the difference between essential
and nonessential amino acids.

Back 28

Amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle are
termed glucogenic or glycogenic. Amino acids whose catabolism yields either acetoacetate or one f its
precursor, (acetyl CoA or acetoacetyl CoA) are termed ketogenic. Leucine and lysine are exclusively ketogenic.

Nonessential amino acids can be synthesized in sufficient amounts from the intermediates of
metabolism or, as in the case of cysteine and tyrosine, from essential amino acids.
Essential amino acids cannot be synthesized in sufficient amounts by the body and therefore must be
obtained from the diet in order for normal protein synthesis to occur.

Front 29

Catabolism of carbon skeletons of amino acids.

Back 29

1. Amino acids that form oxaloacetate:
Asparagine: hydrolyzed by asparaginase, liberating ammonia and aspartate. Asparaginase
can be used to treated acute lymphoblastic leukemia (ALL) patients
2. Amino acids that form α-ketoglutarate:
a) Glutamine b) Proline c) Arginine d) histidine: intermediate N-forminminoglutamate (FIGlu)
can be used to detect the deficiency of folic acid
3. Amino acids that form pyruvate:
a) Alanine b) Serine c) Glycine d) Cystine e) Threonine
4. Amino acids that form fumarate:
Phenylalanine and tyrosine: Phenylalanine is hydroxylated by phenylalanine
hydroxylase to form tyrosine. Tyrosine then form fumarate and acetoacetate. PKU
5. Amino acids that form succinyl CoA: Valine, Isoleucine, Threonine and Methinoine:
Methionine is converted to S-adenosylmethionone (SAM), which is the major methyl-group
donor in one-carbone metabolism. SAM is hydrolyzed to homocysteine and adenosine.
Homocysteine has two fates:
a) Resynthesis of methionine: Homocysteine accepts a methyl group from N5-methyl-
THF to form methionine. This reaction requires the coenzyme methylcobalamin (from
vitamine B12).
Notes for chapter 20: Amino acid degradation and synthesis
2
b) Synthesis of cysteine: homocysteine combines with serine to form cystathionine,
which is hydrolyzed to α-ketobutyrate and cysteine. A reaction requires the coenzyme
B6 (pyridoxine).
6. Catabolism of the branched-chain amino acids: Leucine, Valine and Isoleucine. Three similar
steps: transamination, oxidative decarboxylation and dehydrogenation. Decarboxylation is
mediated by branched-chain α-keto acid dehydrogenase. Deficiency of this enzyme results in
maple syrup urine disease.

Front 30

Why can asparinase be used to treat leukemic patients? Why can the FIGlu excretion test be used to
diagonize folic acid deficiency.

Back 30

asparaginase hydrolyzes asparagine, liberating ammonia and aspartate. Asparagine is essential for leukemic dividing cells.

Patients deficient in folic acid excrete FIGlu in urine, especially after histidine. Normally, with folic acid, FlGlu becomes glutamate

Front 31

What are the two reactions using the B12 derivatives as coenzymes?

Back 31

Resynthesis of methionine from homocysteine as described above. Using B12
derivative. Another reaction using vitamin B12: some amino acids, like Val and Ile and
Met, give rise to proprionyl CoA. This is carboxylated, using biotin, and then
rearranged, using B12 derivative, to give succinyl CoA

Resynthesis of methionine: Homocysteine accepts a methyl group from N5-methyl-
THF to form methionine. This reaction requires the coenzyme methylcobalamin (from
vitamine B12).

Front 32

Catabolism of methionine: degradation and resynthesis of methionine.

Back 32

Methionine is converted to S-adenosylmethionone (SAM), which is the major methyl-group
donor in one-carbone metabolism. SAM is hydrolyzed to homocysteine and adenosine.
Homocysteine has two fates:

Front 33

What are the two fates of
homocysteine?

Back 33

a) Resynthesis of methionine: Homocysteine accepts a methyl group from N5-methyl-
THF to form methionine. This reaction requires the coenzyme methylcobalamin (from
vitamine B12).

b) Synthesis of cysteine --> succinyl CoA: homocysteine combines with serine to form cystathionine,
which is hydrolyzed to α-ketobutyrate and cysteine. A reaction requires the coenzyme
B6 (pyridoxine). Then it becomes succinyl CoA. This requires B12

Front 34

Homocystinuria is due to the deficiency of which enzyme.

Back 34

cystathionine B-synthase

Front 35

What are the corresponding keto acids for the formation of alanine, aspartate and glutamate?

Back 35

pyruvate
oxaloacetate
alpha-ketoglutarate

Front 36

What is the cause for Maple syrup disease?

Back 36

Branched-chain-ketoacid dehydrogenase deficiency. Branched
chain amino acids and ketoacids accumulate in plasma and urine. Neurological problems.
Mortality high.

Front 37

In addition to the deficiency of phenylalanine hydroxylase, what else can cause PKU? Why?

Back 37

1. Causes: Usually due to deficiency of Phe hydroxylase but can also be due to deficiency in
BH2 synthetase or BH2 reductase.

Front 38

Which reactions require the BH4 as a coenzyme? What is the source of BH2?

Back 38

Biosynthetic reaction involving amino acids and tetrahydrobiopterin (BH4)
a) Tyrosine synthesis
b) Catecholamine synthesis
c) Serotonin synthesis

Front 39

How to treat PKU?

Back 39

Clinical treatment different since neurological effects of last two not helped by
restricting phenylalanine in diet. Give BH4 or 3,4-dihydroxyPhe and 5-hydroxyTrp.
Treatment: judiciously limit Phe but not too much since essential. Give Tyr in diet.

Front 40

What is the rate-controlling step in heme synthesis?

Back 40

glycine and succinyl CoA --> ALA by ALA synthase. ALA
synthase is inhibited by hemin, which results from oxidation of Fe2+ to Fe3+ in heme, caused
by too much porphyrin synthesis without enough globin to put it into.

Front 41

How is the activity of ALA synthase regulated?

Back 41

Synthesis begun by reaction of glycine and succinyl CoA catalyzed by ALA synthase. ALA
synthase is inhibited by hemin, which results from oxidation of Fe2+ to Fe3+ in heme, caused
by too much porphyrin synthesis without enough globin to put it into.

Front 42

What are the targets of lead?

Back 42

Ferrochelatase, inserts Fe2+. Ferrochelatase and ALA dehydrase are lead sensitive so that
coproporphyrin III and ALA accumulate in the urine.

Heavy metal ions inhibit ALA dehydratase. The reaction is the condensation of 2 ALA --> porphobilinogen.

Front 43

What causes phorphyria? How to treat it?

Back 43

a. defects in heme synthesis, usually congenital. Usually accumulate porphyrins
or porphyrin precursors.
b. If tetrapyrrole intermediates accumulate, often photosensitivity probably due to
porphyrin-mediated formation of superoxide radicals from oxygen. Damage
membranes and release enzymes from lysosomes. Get increase in ALA
synthetase activity since heme deficient so more intermediates (prior to block)
c. Therapy: intravenous injection of hemin, avoidance of sunlight and ingestion
of antioxidants like β-carotene
d. Porphyria cutanea tarda: The most common porphyria with a deficiency in
uroporphyrinogen decarboxyase

Front 44

What is the major source of heme proteins?

Back 44

Senescent red blood cells

Front 45

What is the end product of heme degradation? How is it
excreted from the body?

Back 45

urobilinogen turns into stercoblin (stool pigment) and urobilin (urine pigment).

Front 46

What is jaundice? What might cause jaundice?

Back 46

1. Yellow color of skin, nail beds and whites of eyes
2. Hemolytic: due to massive hemolysis so get unconjugated bilirubin in blood
3. Obstructive: Due to the obstruction of bile duct: hepatic tumor or bile stone
4. Hepatocellular: damage to liver cells: cirrhosis or hepatitis

Front 47

What are the precursors of catecholamines? How are they degraded?

Back 47

tyrosine and dopa
MAO and COMT

Front 48

What are the sources for creatine, histamine and serotonin?

Back 48

V. Creatine. See figure 21.19.
1. Regenerate ATP in muscle from creatine phosphate
2. Synthesis involves S-AdoMet
3. Spontaneously cyclizes into creatinine, an estimator of muscle mass and so of potential kidney
malfunction and paralysis or muscular dystrophy
VI. Histamine: powerful vasodilator, secreted due to allergic reactions or trauma. See figure 21.17.
1. Secreted by mast cells as a result of allergic reactions or trauma
2. It is formed by decarboxylation of histidine.
3. allergic and inflammatory reactions, gastric acids secretion and possible neurotransmission in
parts of the brain.
VII. Serotonin. See figure 21.18.
1. 5-hydroxytryptamine
2. Most found in cells of the intestinal mucosa.
3. synthesized from tryptopan
4. +pain perception, affective disorders and regulation of sleep, temperature, and blood pressure.

Front 49

What is the difference between nucleoside and nucleotide?

Back 49

2. Nucleoside: the addition of a pentose sugar (ribose or 2-deoxyribose) to a base produces a
nucleoside.
3. Nucleotide: monophosphate, diphosphate, or triphosphate esters of nucleoside

Front 50

What is the unique pyrimidine for DNA and RNA?

Back 50

Thymidine and uridine

Front 51

What are the different sources for the carbons and nitrogens in the purine ring?

Back 51

N: Glycine, Aspartame, Glutamine
C: N-10 formyl tetrahydrofolate, CO2

Front 52

What is the rate-limiting step in the purine synthesis? How is it regulated?

Back 52

Synthesis of 5’-phosphoribosylamine from PRPP and glutamine: committed step, inhibited
by AMP, GMP, IMP and activated by PRPP

Front 53

How do PABA analogs (sulfonamides) and folic acid analogs (methotrexate) inhibit the purine synthesis?

Back 53

Sulfonamides are structural analogs of PABA the competitively inhibit bacterial synthesis of folic acid. Becuase purine synthesis requires tetrahydrofolate as a coenzyme, the sulfa drugs slow down this pathway in bacteria. Humans do not synthesize folic acid.

Methotrexate and related compounds inhibit the reduction of dihydrofolate to tetrahydrofolate, catalyzed by dihydrofolate reductase. These drugs limit tetrahydrofolate, used in purine synthesis. This slows down DNA replication and is useful in treating cancer, but is toxic to all dividing cells.

Front 54

How does mycophenolic acid inhibit the proliferation of T and B cells?

Back 54

reversible, uncompetitor of IMP dehydrogenase. Deprives T and B cells of nucleic acids. Prevents skin graft rejection.

Front 55

What is the cause of LESCH-NYHAN syndrome? How is the activity of ribonucleotide reductase
regulated?

Back 55

Lesch-Nyhan syndrome Figure 22.10
a) Disorder in hypoxanthine-guanine phosphoribosyltransferase (HGPRTase deficiency)
b) Get excess uric acid
c) Get increased PRPP and less IMP and GMP so more de novo purine synthesis

Front 56

What is the end produce of purine degradation? What causes gout? How to treat it?

Back 56

uric acid.
Overproduction or underexcretion of uric acid. This leads to deposition of monosodium urate crystals in joints and inflammation.
1) Mutation in the PRPP synthetase gene (Enzyme resistance to feedback, high
Vmax, low Km for PRPP synthetase)- Higher PRPP levels --> synthesis of
purine nucleotides--> high levels of uric acid

Treatment: prevention of deposition of urate crystals
colchicine (decreased granulocytes, neutrophil effect only)
allopurinol (inhibits xanthine oxidase and uric acid production)
probenecid and sulfinpyrazone (increased uric acid excretion)

Front 57

Why does the deficiency of adenosine deaminase cause severe combined immunodeficiency disease?

Back 57

Accumulation of adenosine --> dATP levels up --> inhibit ribonucleotide reductase (
Fig. 22.12) --> DNA synthesis inhibited
c) Affects T cells and B cells --> immunodeficiency: the impairment of DNA repair due to
the imbalanced levels of dNTPs leads to an accumulation of DNA breaks in the cell
genome, which eventually triggers apoptosis of T and B cells
d) dATP also inhibits the activity of S-adenosylhomocysteine hydrolase, leading to the
accumulation of AdoHcy and the inhibition of methylation reactions that use SAM as
methyl donor.

Front 58

What are the different sources for the carbons and nitrogens in the pyrimidine synthesis?

Back 58

Glutamine, CO2, aspartic acid

Front 59

What causes orotic aciduria?

Back 59

orotic aciduria is due to deficiency of the combination enzyme that metabolizes
orotate

Front 60

How does 5-fluorouracil inhibit DNA replication?

Back 60

Thymine
analogs 5-fluorouracil inhibits tumor growth by irreversibly binding to and inhibiting the thymidylate synthase (suicide inhibitor).
Methotraxate also inhibits this reaction.

Front 61

High yield: What controls the release of insulin and glucagon?

Back 61

Glucose (most important), Amino acids, Gastrointestinal hormones (secretin & others), and epinephrine.

Front 62

High yield: Which cells make insulin? Glucagon?

Back 62

β-cells of the Islets of Langerhans

α-cells of pancreatic islets

Front 63

In general, how do the actions of insulin and glucagon differ
from each other?

Back 63

Insulin decreases blood glucose
Glucagon increases blood glucose

Front 64

High yield: What are the main target organs for insulin and glucagon?

Back 64

liver (most important, especially for glucagon)
muscle and fat tissue glucose uptake
insulin Inhibits hormone-sensitive lipase in adipocytes

Front 65

high yield: What is hypoglycemia and what causes it?

What blood glucose level is the threshold?

Why does it cause these symptoms and how do you treat it?

Back 65

low blood glucose
a) insulin-induced
b) postprandial
c) fasting
d) alcohol intoxication

40 mg/dL

Impaired glucose delivery to brain

– Short term control: increased glucagon & epinephrine;
decreased insulin.
– Long term: increased cortisol and growth hormone.

Front 66

What are the hormonal responses to a carbohydrate-rich
meal, and how does this condition differ from fasting?
Which pathways of carbohydrate utilization are stimulated
or down-regulated in each condition?

Back 66

After meal: High insulin/glucagon ratio
After meal: glycogen, FA, and protein synthesis increase
Fasting: high glucagon, low insulin
Fasting: protein degrad, gluconeo, FA degrad
Fuel Usage: glu --> glycogen --> protein --> fat

Front 67

High yield: What hormonal changes (insulin/glucagon) cause or
accompany diabetes?

Back 67

deficiency of insulin, insulin resistance,

Front 68

High yield: What are the two main types of diabetes, and the main
types of treatment?

Back 68

Type 1 diabetes- autoimmune destruction of Beta cells
Type 2- resistance to insulin action, and β-cells not producing enough insulin

increasing insulin, insulin sensitivity, or decreasing release of glucose

Front 69

What is HbA1C and how is it used in monitoring diabetic
patients? What advantage does its measurement have
over measuring blood glucose levels?

Back 69

HbA1C (a Hb covalently modified by glucose—non-enzymatically glycosylated)

don't need to fast?

Front 70

High yield: What are macronutrients and what are micronutrients?

Back 70

! Macronutrients: fat, carbohydrate, protein (You need a lot)
! Micronutrients: vitamins, minerals (You need less)

Front 71

High yield: What is the calorie content (kcal/g) of the different types of foods?

Back 71

< carbohydrate: 4 kcal/g
< protein: 4 kcal/g
< fat: 9 kcal/g
< alcohol: 7 kcal/g

Front 72

Which vitamins are fat soluble? Which vitamins can be toxic in overdose?

Back 72

ADEK

Everything except for E

Front 73

What is the methyltetrahydrofolate trap" hypothesis?

Back 73

cobalamin defici causes a build ip of cofactor methyl-tetrahydrofolate which deprives the body of other tetrafolate forms

Front 74

What causes pernicious anemia, and how is it treated?

Back 74

B12 absorption deficiency

monthly B12 injection, or high oral doses of B12

Front 75

What is folic acid used for?

Back 75

biosynthesis of purines, pyrimidines, and some amino acids. catabolism of odd numbered fats.

deficiency: neural tube defects, Hyperhomocysteinemia, growth failure

Front 76

What is the purpose of Cobalamin (B12)?

Back 76

methyl transfer reactions

deficiency causes "methyltetrahydrofolate trap"

Front 77

What are the symptoms of pernicious anemia? What will treat the anemia, but not the neuropsych?

Back 77

anemia and later neuropsychiatric symptoms
folic acid

Front 78

What is retinol used for? Retinal?

Back 78

vision, reproduction, growth, epithelial tissue maintenance

light receptor in vision

Front 79

What does Vitamin D do?

Back 79

steroid hormone molecule that regulates calcium & phosphorus homeostasis; active form is
3 1,25-dihydroxyvitamin D which is made in the kidney in response to parathyroid hormone.

Front 80

Which vitamin is a cofactor in carboxylation reactions

Back 80

Biotin

Front 81

Which vitamin is a cofactor in alpha carboxylation of blood clotting proteins?

Back 81

Vitamin K

Front 82

Which fat soluble vitamin mainly functions as an antioxidant?

Back 82

Vitamin E

Front 83

Where does the last step of 1,25-dihydroxyvitamin D3 hydroylation occur?

Back 83

kidney

Front 84

Which vitamin deficiency occurs primarily in neonates?

Back 84

K

Front 85

High yield: What blood glucose level indicates diabetes?

Back 85

126 mg/dL fasting on two tests

Front 86

Why is fiber so good?

Back 86

Fiber is non-digestible carbohydrate (cellulose, lignin, and pectin). Normalizes stools, reduces
hemorrhoids, decreases bowel exposure to carcinogens; soluble fiber can lower cholesterol.

Front 87

High yield: What is the major symptom of vitamin D deficiency? Why can renal failure be accompanied by rickets?

Back 87

osteomalacia or rickets
the last hydroxylation of vitamin D happens in the kidney

Front 88

High yield: What are the 3 major roles of vitamin A?

Back 88

an ingredient of visual pigment
signaling/hormone-like functions involved in maintaining the integrity of various epithelia
antioxidant properties

Front 89

What causes beriiberi and wernicke-korsakoff?

Back 89

thiamine (b1) deficiency

Front 90

What enzyme is low in the XX female psuedohermaphrodite?

Back 90

21-hydroxylase

Front 91

Which steroids will be deficient in this female psuedohermaphrodite? Which steroids will be overproduced? Why?

Back 91

elevated 17-hydroxyprogesterone and testosterone
low cortisol

21-hydroxylase deficiency

Front 92

What hormone secreted by the hypothalamus stimulates glucocorticoid production by the adrenals? What kind of hormone is it?

Back 92

ACTH

Front 93

Why does Andrew have adrenal hyperplasia. Why is it reversed when glucocorticoids are given?

Back 93

Too much ACTH
glucocorticoids and mineralicorticoids re-establish pathway control preveninting excess 17-OH progesterone

Front 94

How do you withdraw a patient from high-dose glucocorticoid treatment?

Back 94

slowly and stepwise

Front 95

Which lipoproteins are harmful? Which are protective?

Back 95

LDL
HDL

Front 96

How is LDL taken up by cells? What regulates this process?

Back 96

surface receptors take up LDL for endocytosis. LDL receptors

Front 97

What is the rate-limiting enzyme in cholesterol biosynthesis? What drugs target this enzyme? How do these drugs cause a decrease in LDL levels?

Back 97

HMG CoA reducatase
HMG CoA reducatase inhibitors
they compete with HMG CoA reducatase to prevent melvonate which is a precursor to cholesterol

Front 98

How do bile acid sequestrants work? Can you name one?

Back 98

cholestyramine blocks reabsorption of bile salts for use as a source of exogenous cholesterol

Front 99

How do you treat a patient heterozygous for mutations in the LDL receptor? What about a homozygous patient?

Back 99

statins
cholestyramine- bile acid sequestrant

homozygous would be dead

Front 100

Understand the basic biochemistry behind marasmus versus kwashiorkor.

Back 100

marasmus- general malnutrition
kwashiorkor- lack of protein

Front 101

Why do children with kwashiorkor have edema?

Back 101

no protein --> no albumin --> no oncotic pressure --> edema

Front 102

Why do kwashiorkor patients have fatty livers?

Back 102

aflatoxin causes liver failure

Front 103

How is aflatoxin is converted into a DNA damaging metabolyte? Review cytochrome P450 enzymes.

Back 103

hydroxylation of aflatoxin B1 by P450 monooxygenase system in the presence of O2 and NADPH leads to aflatoxin epoxide

Front 104

How do you treat patients with kwashiorkor?

Back 104

Smaller protein supplements slowly to accomodate damaged liver's reduced protein detox capacity

Front 105

How does nitrogen (ammonia) enters the cycle and how it is converted into urea?

Back 105

ammonia + CO2 --> carbamoyl phosphate

Arginine is then cleaved to make urea and ornithine, almost exclusively in the liver

Front 106

Understand the biochemical and metabolic consequences of the genetic defect in arginosuccinate synthetase

Back 106

inadequate urea synthesis and disposal of ammonia

Front 107

How should this patient be treated in the short term and in the long term?

Back 107

short term- hemodialysis to reduce plasma ammonia to prevent brain damage
long term- reduce protein intake and allow alternative rous for nitrogen excretion: phenylacetate and arginine

Front 108

Understand the rationale behind treating the patient with phenylacetate, arginine, and benzoate.

Back 108

Phenylacetate combines with glutamine and is excreted as phenylglutamine
Arginine picks up NH4 and is excreted. It also encourages the urea cycle.
Benzoate binds glycine and is excreted

Front 109

What metabolites will accumulate in a patient with insufficient vitamin B12?

Back 109

methylmalonic acid, homocysteine

Front 110

Understand the metabolic block in phenylketonuria

Back 110

block of conversion of phe to tyrosine by phenylalanine hydroxylase

Front 111

How do you treat phenylketonuric patients? What must they avoid in their diet?

Back 111

Low PKU diets

Front 112

Should you put a patient on a diet with zero phenylalanine?

Back 112

No, it's an essential nutrient

Front 113

What about tyrosine in this patient?

Back 113

tyrosine is low in the patient, supplement in diet

Front 114

What important metabolites of phenylalanine/tyrosine will be deficient in an untreated phenylketonuric?

Back 114

tyr, dopamine, noradrenaline

Front 115

Why should PKU patients avoid aspartame?

Back 115

high levels of PKU in it

Front 116

What enzyme activities would be deficient in Simon K. (normal iron levels, but anemic)? What about his occupation would cause this deficiency?

Back 116

Foundry worker --> lead poisoning
beinds to thiol groups of cysteine residues in proteins, inhibits reactions involving these enzymes
Example: Ferrochelatase and amino-laevulinic acid

Front 117

How would you treat Simon K. (lead poisoning)?

Back 117

chelation therapy

Front 118

How would you treat Jane D.(anemia with low iron)?
Why give ascorbic acid (vitamin C) along with iron tablets to Jane? That is, what is the chemical/biochemical basis for this?

Back 118

ferrous sulphate and vitamin C (malnutrition)
Dietary acid must be reduced to ferrous form from the ferric form

Front 119

Understand in very general terms how MPTP is processed into a neurotoxic chemical in vivo.

Back 119

MPTP --> MPDP+ --> MPP+ (toxic) by MAO in glial cells
MPP+ is good substrate for dopamine receptors. Kills presynaptic neuron.

Front 120

What does MPP+ damage? What does this lead to?

Back 120

MPP+ is good substrate for dopamine receptors in presynaptic membrane of neurons

Front 121

Randy B. was treated with L-DOPA, carbidopa and bromocryptine. What is the biochemical basis for the action of each of these drugs, and how would they help him?

Back 121

bromocryptine- stimulates dopamine receptors
L-Dopa (precursor) --> additional dopamine
carbidopa prevemts metabolism of DOPA to dopamine in periphery

Front 122

PTH and Vitamin D:
Where are these hormones made?
What controls their synthesis/release?
What tissues do they act on?
What is the phenotype of deficiencies in these hormones?

Back 122

Parathyroid and Liver/Kidney
hypocalcemia

(1) increasing the uptake of calcium from the gut into the blood, (2) decreasing the transfer of calcium from blood to the urine by the kidney, and (3) increasing the release of calcium into the blood from bone.

convulsion, muscle cramps, virilisation, skeletal abnormalities, but normal mineralisation

Front 123

Understand, in general terms, how G-protein-coupled receptors work, and why this patient had a general failure in response to certain hormones (as well as diminished sense of smell, etc).

Back 123

G proteins are conserved over a variety of systems: PTH, olfaction, glucagon

Front 124

Understand the biochemical basis for the differences between type I and type II diabetes

Back 124

Type I autoimmune destruction of B cells
Type II- lack of reaction to insulin

Front 125

What is insulin resistance? Which type of diabetes does it typically occur in?

Back 125

a lower response to dose
type II

Front 126

Why is this patient insulin resistant?

Back 126

change in recognition site of insulin receptor, decrease in insulin binding capacitance

Front 127

What sort of signal does the insulin receptor transduce?

Back 127

tyrosine kinase

Front 128

What does B3 reduce?

Back 128

athlersclerosis, LDL, VLDL