SM02 Mini2 Flashcards Preview

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Flashcards in SM02 Mini2 Deck (228):
1

what causes acute pancreatitis?

accidental activation of pancreatic enzymes in the pancreas

potentially fatal

2

sucrose

alpha-D-glucopyranosyl-(1→2)-beta-D-fructofuranose

3

lactose

beta-D-galactopyranosyl-(1→4)-beta-D-glucopyranose

4

maltose)

alpha-D-glucopyransyl-(1→4)-alpha-D-glucopyranose

5

glycogenic bonds

alpha(1→4) every 8-12 residues

alpha(1→6) at branch points

6

how is amylopectin different than glycogen?

branching occurs every 24-30 residues in amylopectin

7

salivary alpha-amylase

  • endoglycosidase: cleaves internal glycosidic bonds
  • cleaves alpha(1→4) glycosidic bonds in starch
  • doesn't recognized di- & trisaccharides or alpha(1→6) bonds
  • products: glucose, maltose, maltotriose, & alpha-limit dextrins
  • functional at pH 6.75-7.0 & denatured in stomach
  • main function: clean teeth of residual food

8

maltotriose

glucose x3

9

alpha-limit dextrin

oligosaccharide w/alpha(1→6) glycosidic bond

10

levansucrase

bacterial enzyme that breaks down sucrose into glucose & fructose

fructose is used for for biofilm aka dental plaque

glucose is used for bacterial glycolysis

11

lysozyme

  • endoglycosidase: hydrolyzes beta(1→4) glycosidic bonds in peptidoglycan (bacterial cell walls)
  • causes bacterial cell death
  • gram- (different peptidoglycan component) and normal mouth flora are resistant

12

pancreatic alpha-amylase

  • not a zymogen, even though it comes from pancreas
  • isozyme to salivary alpha-amylase
  • completes starch & glycogen breakdown into maltose & other oligosaccharides

13

glucoamylase

  • brush border enzyme
  • exoglycosidase: cleaves ends of molecules
    • nonreducing end of starch
    • alpha(1→4) glycosidic bonds
  • cleaves maltose & maltotriose

14

dextrinase

cleaves dextrins

brush border enzyme

15

sucrase-isomaltase

  • bifunctional enzyme
    • inserted into brush border membrane as one polypeptide chain
    • hydrolyzed into 2 by pancreatic proteases
    • reassociate noncovalently
  • sucrase unit cleaves sucrose, maltose, & maltotriose
  • isomaltose cleaves alpha(1→6) glycosidic bonds in isomaltose & alpha-limit dextrins

16

maltase

brush border enzyme

cleaves maltose into 2 glucose

17

lactase-cerebrosidase

  • brush border enzyme
  • single enyme w/2 catalytic domains
  • lactase domain
    • cleaves lactose
    • cleaves cellobiose into 2 glucose
  • cerebrosidase domain
    • cleaves glucocerebroside & galactocerebroside (glycosphingolipids)

18

trehalase

brush border enzyme

cleaves trehalose (disaccharide common in mushrooms & insects) into 2 glucose molecules

19

why does lactose intolerance occur?

mutation in the promoter region of the gene encoding the enzyme

20

how does the lactose tolerance test work?

  1. blood concentration of glucose testing
    • before & after ingestion of 50g of lactose
    • if blood glucose concentration increases <20mg/100mL than delay in absorption= + for intolerance
  2. breath test
    • hydrogen concentration in breath measured before & after ingestion of oral lactose
    • if hydrogen concentration increases→ increased fermentation→ + for lactose intolerance

21

Pepsin

  • optimum pH 1.5-2.0
  • endopeptidase: cleaves nonterminal peptide bonds
    • amino side of hydrophobic amino acids
      • gly, ala, val, leu, ile, phe, pro, met, trp
    • aspartate protease
  • hydrolyzes 10-15% of ingested protein
  • produces peptone (mix of oligopeptides & free amino acids)

22

trypsin

  • produces by pancrease as trypsinogen
  • activated in small intestine by enteropeptidase or trypsin
  • endopeptidase:
    • cleaves peptide bonds on carboxyl side of lys & arg, except when followed by pro
    • serine protease

23

enteropeptidase

duodenal produced & secreted serine protease that activates trypsinogen into trypsin

24

trypsin inhibitor

small polypeptide produced by the pancreas to bind & inhibit trypsin

just in case trypsin is activated in pancreas

protects pancreas from activated trypsin

25

chymotrypsin

  • produced and secreted as chymotrypsinogen by the pancreas
  • activated in small intestine
    • cleaved by trypsin into 2 pi-chymotrypsin
    • pi-chymotrypsin or alpha-chymotrypsin cleaves pi-chymotrypsin into alpha-chymotrypsin
    • both forms are active
  • endopeptidase
    • cleaves on carboxyl side of hydrophobic amino acids
    • serine protease

26

elastase

  • produced & secreted by pancrease as proelastase
  • activated in small intestine by trypsin
  • endopeptidase
    • cleaves on carboxyl side of small amino acids (ala &gly)
    • serine protease

27

carboxypeptidase

  • produced & secreted by pancreas as procarboxypeptidase
  • activated in small intestine by trypsin
  • exopeptidase
    • cleaves off one amino acid from C-terminus
      • A: hydrophobic amino acids 
      • B: basic amino acids
    • Zn2+ metalloprotease

28

aminopeptidase

  • brush border enzyme
  • exopeptidase
    • cleaves on amino acid at a time from N-terminus

29

what are the protein brush border enymes in the small intestine?

endopeptidases

carboxypeptidases

aminopeptidase

dipeptidase

30

dipeptidase

  • brush border enzyme
  • exopeptidase
    • cleaves peptide bond in dipeptides

31

ligual lipase

  • present in saliva
  • cleaves small percentage of dietary fat into monoglycerides, diglycerides, & free fatty acids

32

gastric lipase

acid-tolerant enzyme

digests 10-20% of dietary fat

cleaves triglycerides into fatty acids, monoglycerides, & diglycerides

33

bile salts

  • steroid-based acids
  • usually compounded w/a cation (Na+)
  • produced & secreted by hepatocytes & stored in gallbladder
  • emulsify fats
    • nonpolar region of bile salt clings to fat
    • polar region of bile salt repel one another & interact w/water
    • formation of micelles
    • mixed micelles transport lipids thru unstirred layer to mucosa
  • also necessary for absorption of cholesterol & fat-soluble vitamins

34

pancreatic lipase

produced & secreted by pancreas

binds to surface of fat emulsion droplets in small intestine

cleaves triglycerides into 2 free fatty acid anions & 1 2-monoacylglycerol

35

colipase

produced & secreted by pancreas as procolipase

activated in small intestine by tyrpsin

co-enzyme that functions to maintain activity of pancreatic lipase in presence of bile salts

36

causes of fat malabsorption

pancreatic failure

lack of bile salts (biliary obstruction or reduced production)

extensive intestinal dz

37

steatorrhea

presence of bulky fatty floating stoool that contains undigested triglycerides

38

pancreatic nucleases

consist of DNAses, RNAses, exonucleases, & endonucleases

breakdown of nucleic acids into monomeric nucleotides

39

what brush border enzymes break down nucleic acids?

  • nucleosidases
    • cleaves ribose or deoxyribose from nitrogenous base
  • phosphatases
    • cleaves phosphate groups from nucleoside

40

protein & energy malnutrition is often accompanied by?

micronutrient deficiencies

electrolyte imbalances

metabolic disorders

41

fat malabsorption is the main cause of which vitamin deficiencies?

A, D, E, & K

42

which vitamins can become toxic?

excesses of vitamin A, vitamin D, vitamin K, niacin, & pyridoxine (B6)

43

what is the main function of most water-soluble vitamins?

as essential coenzymes

44

what are the main dietary risks in the US?

excessive levels of fat, salt, & sugar

reduced fiber intake

45

what is the importance of vitamin C?

aka ascorbic acid

reducing agent

  • used as a cofactor
    • collagen hydroxylation in the formation of hydroxyproline
    • antioxidant
    • iron absorption

stress depletes its stores in adrenals

46

dz of vitamin C deficiency

scurvy

signs & symptoms: bruised skin, muscle fatigue, swollen gums, decreased wound healing, hemorrhaging, osteoporosis, & anemia

47

importance of thiamin

amino acid catalysis

oxidative decarboxylation of alpha-ketoacids & aldehyde transfers

pentose phosphate pathway

48

who is most at risk for thiamin deficiency?

alcoholics

49

how are thiamin levels assessed?

by erythrocyte transketolase rxn

50

Beri-Beri

cause: thiamin deficiency

signs & symptoms: mild GI complaint, weakness & burning sensation in feet, severe muscle weakness, wasting, delirium, & memory loss

51

Wernicke-Korsakoff Syndrome

cause: long-term thiamin deficiency; poor uptake & inadequate diet

signs & symptoms: metal derangement & delirium, ataxia

common in homeless

52

importance of riboflavin

redox reactive

converted to FMN &FAD in tissues

53

signs & symptoms of riboflavin deficiency

glossitis, angular stomatitis, sore throat, wet dermatitis of nose & scrotum

normochromic, normocytic anemia

54

Pellagra

cause: niacin deficiency

signs & symptoms: 4 D's: dermatitis, dementia, diarrhea, death

acute deficiency ressembles sunburn

55

importance of niacin

converted to active: NAD+ & NADP+

56

importance of B6

coenzyme for amino acid rxns

3 dietary forms: pyridoxal, pyridoxamine, & pyridoxine

57

what causes vitamin B6 deficiency?

oral contraceptives can interfere w/absorption

alcoholism

58

importance of folate

one-carbon carrier as tetrahydrofolate (THF)

dihydrofolate reductase needed for DNA synthesis

59

cause & effect of folate deficiency

cause: late pregnancy, alcoholism, or intestinal malabsorptive syndrome

effect: megaloblastic anemia

60

importance of vitamin B12

aka cobalamin

cobalt bearing tetrapyrrole

required for methylmalonyl-CoA mutase & methionine synthase enzyme catalysis

61

importance of biotin

required for ATP-dependent carboxylases

found covalently boudn to lysyl-residues

62

importance of pantothenate

part of coenzyme A

functions in fat & 2-carbon metabolism

63

importance of choline

de novo synthesis is not adequate for demand for phosphatidylcholine production

source of S-adenosylmethionine methyl groups

64

who is most at reisk for vitamin A deficiency?

elderly & urban poor

fat malabsorption syndromes

overuse of laxatives w/mineral oil

65

cause of night blindness

vitamin A deficiency

66

importance of vitamin D

aka calcitriol

calcium & phosphorus homeostasis

in concert w/PTH & FGF23

67

cause of rickets

soft bones in children

vitamin D deficiency

68

cause of osteomalacia

bone francture in adults

vitamin D deficiency

69

importance of vitamin E

aka tocopherols

scavenge free radicals

especially prevents peroxidation of polyunsaturated membrane fatty acids

70

effect of vitamin E deficiency

erythrocyte fragility

71

importance of vitamin K

aka menaquinones

facilitates in blood clotting process

needed for formation of factor II, VII, IX, X, protein C & S

gamma-carboxy-glutamate functions in calcium chelation

72

cause of vitamin K deficiency

fat malabsorptive disorder or long-term antibiotic use

73

what are the essential fatty acids?

linoleic acid: omega 6 or 18:3:9, 12, 15

alpha-linolenic acid: omega 6 or 18:2:9, 12

arachidonic acid (only if linoleic is absent from diet): omega 6 or 20:4:5, 8, 11, 14

74

what is the role of fatty acids in prostaglandin synthesis?

arachidonic acid is the precursor for prostaglandin 2 class; converted by COX2

eicosapentaenoic acid is the precursor for prostaglandin 3 class as coverted by COX

75

what is the role of fatty acids in thromboxane synthesis?

arachidonic acid precursor for thromboxane A2 via COX1

eicosapentaenoic acid is precursor for thromboxane A3 via COX

76

what is the role of lipoprotein lipase in fat metabolism?

synthesized & found in skeletal muscle, myocardium, lung, spleen, kidney, lactating mammary glands, aorta, & adipose tissue

found on cell membrane facing capillaries

breakdown of triglycerides from chylomicron

77

what control mechanism are in place of lipoprotein lipase?

  • synthesis & activity in increased:
    • in adipocytes during the fed state
      • via insulin
    • in muscle during fasted/exercise state
    • greatly increased in lactating mammary glands
  • decreased in reverse scenarios

78

what is the importance of adipose tissue in fat metabolism?

storage

as 90% of adipose tissue is made of triglycerides

79

how are triglycerides synthesized?

  • glycerol 2-phosphate
  • add saturated acyl group via CoA to C1
  • add unsaturated acyl group via CoA to C2
  • remove C3 phosphate via hydration
  • add acyl chain to C3 via CoA

80

what controls the synthesis of triglycerides?

insulin stimulates triglyceride synthesis in adipocytes

81

what is the function of hormone sensitive lipase?

hydrolyzes stored triglycerides into free fatty acids

82

what controls hormone sensitive lipase?

  1. perilipin A
  2. hormone cascade: increased cAMP→ PKA→ activatio of HSL

83

explain beta-oxidation

  • from carboxyl end of fatty acid
  • dehydrogenation
  • hydration
  • dehydrogenation
  • removal of 2 carbons as acetyl-CoA
  • repeat as needed

84

how is beta-oxidation controlled?

malonyl-CoA (first definitive product in fatty acid synthesis) inhibits CPT1 of the carnitine shuttle thus inhibiting beta-oxidation

85

what controls ketone body production?

insulin: prevents ketone body build up

, glucagon, & epinephrine

86

what are the consequences of ketone body overproduction?

ketone bodies are acidic

their build up in blood results in acidosis

mostly type 1 diabetic as insulin prevents ketone body build up

fruity odor on breath

87

how are fatty acids synthesized?

fatty acid synthase complex: 7 linked enzymes

  • fatty acis synthase acts as starting block on Cys & Pan residues on ACP
  • decarboxylation: cys acyl group transfer to Pan acyl group (2 & 3 C→ 4C + CO2)
  • reductase: pan-distal ketone becomes alcohol
  • dehydratase: loss of water, gain double bond between C2 & C3
  • reductase: saturate (double becomes single)
  • translocase: acyl chain transfered back to Cys residue
  • repeat: malonyl transferase adds new malonyl group to pan to extend fatty acid chain
  • terminated at 16C (palmitate) or 18C (stearic acid)
    • further additions or modifications done elsewhere

88

compare & contrast the synthesis & degradation of fatty acids.

they are the reverse of one another w/one exception

where beta-oxidation releases acetyl-CoA, synthesis reacts with malonyl-CoA & generates CO2

89

what is the rate-limiting step of fatty acids synthesis?

malonyl-CoA synthesis by acetyl-CoA carboxylase from acetyl-CoA, HCO3- & ATP

requires the presence of biotin

90

what controls acetyl-CoA carboxylase activity?

  • activated
    • allosterically by citrate→ dimerizes
    • dephosphorylation
      • insulin
    • upregulated by high ratio of insulin/glucagon
  • inactivated
    • palmitoyl-CoA→depolymerization
    • phosphorylation by cAMP-dependent protein kinase A 
      • glucagon & epinephrine

91

what type of unsaturated fatty acids behave like a saturdated fat?

trans fats

due to transconfiguration rigidity

92

explain the omega naming system of fats.

carbons counted from methyl end of fatty acid chain

# following omega is location of double bond

93

explain delta naming system of fatty acids.

carbons counted from carboxylic end of fatty acid chain

1st # is # of carbons in the chain

2nd # is # of double bonds in chain

3# is location of double bond

94

mechanism of action for glucocorticoids

  • induces lipocortin-1 (annexin-1) synthesis
    • lipocortin-1 suppresses phospholipase A2→ blocking eicosanoid production
    • lipocortin-1 inhibits leukocyte inflammatory events
  • suppresses COX expression

95

role of COX 1

cyclooxygenase

constitutive enzyme

protective role

maintenance of gastric tissue, renal homeostasis, & platelet aggregation

thus COX 1 inhibitors increase risk of ulcers

96

role of COX 2

cyclooxygenase

inducible enzyme

made in response to products of activated immune & inflammatory cells

**this is the one that needs to be inhibited by NSAIDS**

97

compare & contrast TxA2 &TxA3.

Thromboxane A2 & A3

A3 is less potent activator of platelet aggregation→ less likely to cause clot formation

A2 is major activator of clotting cascade & made from arachidonic acid

A3 is made form eicosapentaenoic acid

 

98

what are the signs & symptoms of essential fatty acid deficiency?

scaly dermatitis

hair loss

poor wound healing

infertility due to reduced growth

inability to fight infection

99

how does oxidation of very long chain fatty acids differ from shorter ones?

must first be converted to octanoyl-CoA by acyl-CoA oxidase in peroxisomes

100

causes & symptoms of Zellweger syndrome

  • cause: peroxisome biogenesis defect in all tissues
    • adrenoleukodystrophy
    • very long chain fatty acids cannot pass into peroxisomes
    • very long chain fatty acids accumulate in blood & tissues→ reduces plasmalogens
  • signs/symptoms: adrenocortical insufficiency &  abnormalities of white matter in cerebrum
    • mostly affects CNS, liver, & kidneys

101

cause, symptoms, & treatmen of Refsum's Dz

cause: accumulation of phytanic acid 

symptoms: neurologic

treatment: dietary restriction of green vegetables, ruminant milk, & meat

102

cause, symptoms, & treatment of mathylmalonic acidemia

cause: defective methylmalonyl-CoA mutase OR vitamin B12 deficiency

symptoms: life threatening acidiosis

tx: adenosylcobalamine (B12)

103

how are odd chain fatty acids oxidized?

  • propionyl-CoA carboxylase w/biotin
    • breaks down propionyl-CoA (3 carbon) to methylmalonyl-CoA (4 carbon)
  • methylmalonyl-CoA mutase w/B12
    • breaks methylmalonyl-CoA into succinyl-CoA
    • succinyl-CoA can enter TCA cycle

104

what are ketone bodies?

acetoacetate & beta-hydroxybutyrate

acetone (also spontaneous breakdown product of acetoacetate)

105

cause, signs, & treatment of medium chain acyl-CoA dehydrogenase deficiency

cause: hypoglycin A (Akee fruit toxin) OR autosomal recessive mutant of MCAD allele

effects: decreased ability of fatty acids to serve as fuel, increased omega-oxidation, high levels of 6-10 carbon dicarboxylic acids in urine, high levels of fatty acids in plasma, fat accumulation in liver, impaired activation of pyruvagte carboxylase, 25-60% mortality in early childhood

tx: low fat high carbohydrate diet, avoid long intervals between meals, riboflavin

 

106

cause, signs, & treatment of carnitine or carnitine acyl transferase deficiency

cause: carnitine or carnitine acyl transferase dificiency

effects: decreased rate of transport of long chain fatty acids, increase fatty acids in blood, hypoglycemia, low levels of ketones, muscle weakness & pain, release of myoglobin & CK into blood, high VLDL, impaired gluconeogenesis

tx: high oral doses of carnitine

107

what is the importance of minerals in the body?

most are used as cofactors

but high levels can be toxic

108

what are the important trace minerals?

iodine

selenium

copper

zinc

manganese

fluoride

chromium

molybdenum

109

importance of zinc

required for 300+ enzymes

carbonic anhydrase

DNA polymerase, etc

 

110

what are good dietary sources of zinc?

seafood, eggs, meat, legumes, & cereal

111

effects of zinc deficiency

dysgeusia (loss of taste)

anosmia (loss of smell)

poor wound healing

perioral rash

112

acrodermatitis enteropathica

  • cause: inability to absorb zinc
    • SLC39A gene mutation on chromosome 8 
    • acquired via prepared nutritional program
  • symptoms:
    • pustular dermatitis (skin inflammatin w/pimples)
    • diarrhea
    • abnormal nails

113

importance of copper

elelctron transfer mechnism/ Redox reactions

for healthy nerves & joints

114

what are good dietary sources of copper?

meats

shellfish

nuts

cereal

115

wilson's dz

  • cause: excess copper cannot be released
    • autosomal recessive
    • mutation of ATP7B gene for Cu2+-ATPase
  • symptoms: Cu2+ accumulates in liver & brain
    • dementia
    • Keyser-Fleisher rings: brown rings around iris
    • neuronal movement disorders
    • liver damage
    • very low ceruloplasmin
    • high circulating free Cu2+
  • tx: penicillamine (chelation therapy)

116

Menkes Dz

  • cause: cannot absorb Cu2+
    • X-linked recessive
    • mutation of ATP7A gene for intestinal Cu2+-translocase
  • effects: Cu2+ accumulates in small intestine & kidneys, low levels in brain
    • kinky hair
    • seizures
    • unstable body temperature
  • tx: Cu2+ supplementation, poor prognosis (mortality in first 3 years of life)

117

importance of manganese

ATPases, pyruvate carboxylase, peptidases, etc

healthy bones & cartilage, metabolism, reproductive functions

118

what are good dietary sources of manganese?

grains

nuts

leafy vegetables

soy products

119

what is a results of manganese deficiency?

osteoporosis

120

cause of goiter

iodine deficiency

121

how does selenium deficiency present?

hypothyroidism

122

importance of selenium

oxidoreductase reactions

123

importance of fluoride

hard bones & teeth

124

what are the major phospholipids?

  • phosphatidylserine
    • serine (-OOC-CH-N+H3)
  • phosphatidylcholine (lecithin)
    • CH2CH2N+(CH3)3
  • phosphatidylinositol
    • inositol 6 carbon sugar
  • phosphatidylethanolamine
    • CH2CH2N+H3

125

what is the function of the phospholipids w/in the cell?

used to make all cellular membranes

126

how are phospholipids synthesized?

in all body tissue ER membrane, except erythrocytes

  • glycerol 3-phosphate + acyl-CoA
  • + acyl-CoA→ triglyceride or CDP-diglyceride
    • cytidine diphosphate
  • attach diglyceride to choline, ethanolamine, inositol, or serine

127

what is the role of cytidine nucleotides in phospholipid synthesis?

cytidine triphosphate reacts w/phosphatidate to give CDP-diglceride & PPi

first discriminating step for phospholipids instead of triglycerides

128

how are the phospholipids interconverted?

  • phosphotidylserine becomes phosphatidylethanolamine by loss of CO2 w/help of phopholipase D
  • addition on SAM x3 gives phosphatidylcholine
    • S-adenosyl methionine acts as a methyl donor

129

why is it important to have choline from dietary sources?

because it can be salvaged from glycolytic products but not at sufficient levels

130

what is the function of cardiolipin?

maintain certian respiratory complexes on electron transport chain

131

how is cardiolipin antigenic?

antibodies raised against Treponema pallidum will also recognize cardiolipin

leads to autoimmune dz

132

what are the major phospholipids in lung surfactant?

dipalmitoylphosphatidylcholine

phosphatidylglycerol

cholesterol 

sphingomyelin

133

how can fetal levels of lung surfactant be assessed?

amniotic fluid ratio of dipalmitoylphosphatidylcholine (DPPC) to sphingomyelin

ratio of 2 or more is that of mature lungs

134

structure & function of platelet activating factor

C1=saturated alkyl group, C2=acetyl residue, & C3=CH2CH2N+(CH3)3

  • release from phagocytic cells
  • binds surface receptors of surrounding cells
  • causes platelet aggregation & degranulation
  • creates thrombotic & inflammatory response
  • causes neutrophils & dust cells to produce superoxide radicals

135

deficiency or absence of plasmalogens results in what dz?

absence= Zellweger's dz (death at early age)

deficiency= Alzheimer's dz

synthesized in peroxisomes, but function unknown

136

where are phospholipases found?

cell membrane

lysosomes

pancreatic secretions

snake & bee venom

137

what controls phospholipase A2?

inhibited by glucocorticoids

138

function of glycolipids

  • intercellular communication
    • found on outer leaflet of plasma membrane
    • interact w/extracellular environment
    • abundant in nerve tissue
  • regulation of cellular interaction, growth, & development
  • antigenic determinants of ABO blood groups
  • fetal development

139

cause, effect, & symptoms of Tay Sachs Dz

  • cause: hexosaminidase A enzyme deficiency
    • autosomal recessive
  • effect: GM2 ganglioside accumulation
    • especially in brain nerve cells
  • symptoms
    • mental retardation
    • cherry-red macula
    • early mortality

140

cause, effect, & symptoms of Gaucher Dz

  • cause: glucocerebrosidase deficiency
    • autosomal recessive
  • effect: glucocerebroside accumulation in spleen, liver, bone marrow, & brain
  • symptoms
    • hepatospleenomegaly
    • mental retardation in 2/3 types
    • skeletal disorders & anemia in type 1
  • tx: enzyme replacement therapy

141

cause, effect, & symptoms of Fabry dz

  • cause: alpha-gaglctosidase deficiency
    • X-linked 
  • effect: globoside accumulation in eyes, kidneys, ANS, & CVS
  • symptoms
    • reddish-purple skin rashes 
    • burning sensation in hands

142

cause, effect, & symptoms of Niemann Pick Dz

  • cause: sphingomyelinase deficiency
    • autosomal recessive
  • effect: sphingomyelin accumulation in spleen, liver lungs, bone marrow, & brain
  • symptoms
    • hepatosplenomegaly
    • brain damage
    • jaundice
  • tx: bone marrow transplant

143

cause, effect, & symptoms of Krabbes Dz

  • cause: beta-galactosidase deficiency
    • autosomal recessive
  • effect: galactocerebroside accumulation
    • presence of globoid cells
    • breakdown of myelin
    • destruction of brain cells
  • symptoms
    • mental & motor deterioration
    • deafness
    • blindness

144

cause, effect, & symptoms of Sandoff Dz

  • cause: Hexosaminidase A & B
    • autosomal recessive
  • effect: GM2 & globoside accumulation in brain & organs
  • symptoms
    • severe Tay Sachs
    • cherry-red macula
    • infantile death

145

cause, effect, & symptoms of metachromatic leukodystrophy (MLD)

  • cause: arylsulfatase A deficiency
    • autosomal recessive
  • effect: sulfatide accumulation in nervous system, liver, & kidneys
  • symptoms
    • dementia
    • muscle weakness & wasting
    • convulsions

146

cause, effect, & symptoms of Farber Dz

  • cause: ceraminidase deficiency
    • autosomal recessive
  • effect: ceramide  accumulation in joints, CNS, liver, heart, & kidneys
  • symptoms
    • impaired mental & motor abilities
    • swollen lymph nodes & joints
    • hoarseness

147

how are sphingolipidoses diagnosed?

  • PBMC enzyme activity level
  • histological sampling of affected tissues
  • DNA analysis
  • prenatally via amniocytes or chorionic villi

148

what activates 7alpha-hydroxylase?

cholesterol excretion in bile

occurs when cholesterol is in excess

requires thyroid hormone & vitamin C for activation

149

how are primary bile acids modified to become secondary bile acids?

removal of 1 or 2 -OH groups

150

function of 7alpha-hydroxylase

rate determining step in bile acid synthesis from cholesterol

151

difference between bile acids & bile salts

salts are bile acids conjugated to glycine or taurine by an amide bond between carboxyl of bile acid to amino of amino acid

152

signs/symptoms of bile obstruction

pale stool due to lack of pigments from bile

itching from bile accumulation in blood

jaundice from accumulated bilirubin

153

essential amino acids

PVT Tim Hall

phenylalanine, valine, threonine

tryptophan, isoleucine, methionine

histidine, arginine, leucine, lysine

154

define nitrogen balance

the amount of nitrogen entering & leaving the body is equal

positive balance= more coming in than out

negative balance= more going out than coming in

155

causes of negative nitrogen balance

dietary protein deficiency

essential amino acid deficiency

low-carb diet→ liver will use aa for gluconeogenesis→ excess aa use/metabolism

wasting dz: ex. severe infection or cancer

156

causes of positive nitrogen balance

growth

pregnancy

body building

convalescnce: replacing muscle mass after serious illness

157

role of transamination in amino acid catabolism

removal of nitrogen group by transaminase to alpha-ketoglutarate to form glutamate & alpha-ketoacid

158

what cofactor is needed for transamination?

vitamin B6

pyridoxal phosphate

159

role of oxidative deamination of glutamate in amino acid catabolism

glutamate dehydrogenase

  • forward rxn: oxidation
    • recycle alpha-ketoglutarate
    • formation of NH4+ & NADH
    • with H2O & NAD+
  • reverse rxn: reduction
    • formation of glutamate
    • w/NADPH, H+

160

why is NADPH used for glutamate formation by glutamate dehydrogenase?

because it is a stronger reducing agent than NADH & more abundant inthe cell

NADPH>> NADP+

NAD+>>NADH

161

structure of urea

small, water soluble

not toxic

3x concentration of nitrogen over that in dietary protein

A image thumb
162

role of urea in nitrogen metabolism

nontoxic way to rid the body of ammonia

163

sequence of rxns of urea cycle

pre-cycle rxn: carbamoyl phosphate synthetase

  • ornithine carbamoylase 
  • argininosuccinate synthetase
  • argininosuccinate lyase
  • arginase

164

where is does nitrogen come from in the body?

ammonia for carbamoyl phosphate synthetase comes form intestines

aspartate for urea cycle generated by liver via transamination

165

presentation of urea cycle enzyme deficiencies

encephalopathy, hyperventilation, respiratory alkalosis, cerebral edema→ **w/in days of birth**

often fatal

hyperammonemia w/CNS toxicity 

buildup of substrate from missing enzyme

elevated glutamine blood levels

166

why does urea cycle enzyme deficiency cause cerebral edema?

glial cells try to "mop up" ammonia to prevent cerebral toxicity by formation of glutamine

excessive levels of glutamine in glial cells cause water absorption and swelling

thus cerebral edema

167

how can urea cycle enzyme deificiencies be treated?

  • restriction of dietary protein
  • replacement of essential aa w/their alpha-ketoacids, but requires very large quantity
  • adequate carbohydrate intake/avoid fasting→ avoid metabolizing protein for gluconeogenesis
  • avoid stress & infections→ see above reasoning
  • sterilization of GI tract w/broad spectrum antibiotics
    • GI flora are major source of ammonia
    • but often leads to superbugs (c. diff.) thus only temporary measure
  • lactulose to feed GI bacteria
    • no N in lactulose
    • bacteria will then consume GI ammonia to obtain their N
  • benzoate and/or phenylacetate
    • conjugate w/gly & gln to be excreted by the kidneys

168

how does benzoic acid help to clear the body of ammonia?

  • benzoic acid is activated by HS-CoA (costs ATP)
  • conjugates to glycine 
  • para-amino hippuric acid
  • 100% excreted by kidneys

169

how does phenylbutyrate help to clear the body of ammonia?

  • undergoes beta-oxidation to phenylacetate (active agent, but phenylbutyrate tastes better)
  • activated by HS-CoA at cost of ATP
  • alpha C conjugated to glutamine alpha C
  • excreted as phenylacetylglutamine

170

why is it important to know treatment of urea cycle enzyme deficiencies when they are very rare disorders?

because pt with liver cirrhosis will display limited function of the urea cycle

171

what causes a hepatic coma?

hyperammonemia & encephalopathy in advanced liver cirrhosis

172

who is at risk for liver cirrhosis?

alcoholics

chronic infections (HVB/HVC)

non-alcoholic fatty liver dz

173

why is portal blood diverted around a cirrhotic liver?

portal vein→ hepatic vein pressure gradient is flipped

thus there is no driving force

174

products of amino acid degradation

H2

CO2

urea

175

define glucogenic in terms of amino acid degradation

amino acids that are converted to glucose in the liver

176

define ketogenic in amino acid degradation context.

amino acids that are converted to ketone bodies in the liver

usually only occurs when they can't be converted to glucose

177

which amino acids are purely ketogenic?

leucine & lysine

178

which amino acids are purely glucogenic?

  • alanine
  • cysteine
  • glutamate
  • glutamine
  • aspartate
  • asparagine
  • glycine
  • valine
  • methionine
  • proline
  • serine
  • arginine
  • histidine

179

which amino acid are both glucogenic & ketogenic?

phenylalanine

tyrosine

tryptophan

isoleucine

threonine

180

how are non-essential amino acids synthesized?

by transaminases that are reversible

thus can be used for catabolism & anabolism

181

synthesis of which amino acid can be used to "mop up" ammonia?

glutamine from glutamate via glutamine synthetase

costs 1 ATP

182

most kidney stones contain?

calcium oxalate

oxalate is minor product of glycine breakdown

183

bacteria can form trimethylamine from which amino acids?

glycine

carnitine

choline

**rotten fish smell**

184

what is the cause of non-ketotic hyperglycinemia?

inheritied deficiency of glycine cleavage enzyme

185

how is non-ketotic hyperglycinemia diagnosed?

glycine elevated in blood & CSF

186

how does non-ketotic hyperglycinemia present?

seizures, coma and/or apnea in infants

high mortality

severe neurological deficits & mental deficiency→ cannot learn to sit, stand, walk, etc.

187

how is non-ketotic hyperglycinemia treated?

not effectively

benzoic acid has limited effect

NMDA receptor blocker

188

why do non-ketotic hyperglycinemia patients have severe neurological abnormalities?

gly is an inhibitory neurotransmitter in the brain

also has excitatory effect during co-activator of NMDA receptors

thus some pathways are underactive while others are hyperactive

189

what is the most important methyl group donor for biological methylations?

S-adenosyl-methionine

190

what substance is an important 1C carrier?

tetrahydrofolate (THF)

coenzyme form of dietary folic acid

191

what is the only irreversible THF rxn?

formation of methyl-THF

192

what vitamin deficiency leads to folate deficiency and why?

B12 

b/c it is a required cofactor for the regeneration of THF from methyl-THF

193

how is homocysteine broken down?

combined w/serine

 via cystathionine synthase w/B6 (pyridoxine)

to cystathionine degraded to cysteine

both lead to glucogenic products

194

what is the cause of homocystinuria?

deficiency of cystathionine synthase

195

what are the effects of homocystinuria?

  • osteoporosis: tend to have long bones→ tall
  • ectopia lentis: lens displacement 
  • thromboembolism (arterial & venous)
  • mild mental deficiency/psychiatric problems

196

what is the tx for homocystinuria?

some patients respond to high doses of B6, but also B12 & folate therapy

methionine restriction in diet

197

what other congetial disorder presents similarly to homocystinuria?

Marfan's Syndrome

198

what are the first steps in branched chain amino acid metabolism?

branched-chain= valine, leucine, & isoleucine

transamination, oxidative decarboxylation, then dehydrogenation

199

cause of maple syrup urine dz

deficiency of branched-chain alpha-ketoacid dehydrogenase

autosomal recessive inheritance

200

how is maple syrup urine dz diagnosed?

acculumation of Val, Leu, & Ile & their alpha-ketoacids

included in newborn screening programs

201

why is rigofous dietary restriction of Val, Leu, & Ile required for disability-free survival of maple syrup urine dz patients?

because leucine is neurotoxic

202

what is the clinical course of maple syrup urine dz?

complete enzyme deficiency lead to neonatal encephalopathy & early death

partial enzyme deficiency leads to protein intolerance often treated w/thiamine

203

what are the sources of propionyl-CoA?

catabolism of branched chain amino acids (val, ile, thr, meth)→ about 20% of protein/day

odd chain fatty acid catabolism→ only accounts for 1% of daily fats

204

what is the cause of methylmalonic acidemia?

inherited deficiency of methylmalonyl-CoA mutase

used in last steps of branched-chain amino acid catabolism

205

how can B12 deficiency and methylmalonic acidemia be differentially diagnosed?

they both lead to a build up in methylmalonic acid

but B12 deficiency will also exhibit a build up of methionine

206

how does methylmalonic acidemia present?

episodic metabolic acidosis

can be fatal in infants

207

how is methylmalonic acidemia treated?

adenosyl-cobalamin for pts that cannot synthesize the coenzyme

cautious dietary restriction, avoidance of stress & fasting, use of antibiotics during acute crisis

208

cause of propionic acidemia

deficiency of propionyl-CoA carboxylase

inherited

used in last steps of branched-chain amino acid catabolism

209

how does propionic acidemia present?

recurrent episodic metabolic acidosis w/neurologic complications

210

how is propionic acidemia tx?

biotin rarely helps

cautious dietary restriction, avoidance of stress & fasting, use of antibiotics during acute crisis

211

what reaction requires tetrahydrobiopterin (BioH4)?

phenylalanine hydroxylation to tyrosine

occurs in liver

also requires O2 & generates H2O

212

cause of phenylketonuria

deficiency of phenylalanin hydroxylase

autosomal recessive

makes transamination of phenylalanine major pathway of degradation→ build up of phenylacetate, phenylpyruvate, & phenyllactate

213

how is PKU diagnosed?

newborn blood or urine screening

214

effect of PKU

brain damage

mental retardation

light skin & hair

"mousy" odor of infant

215

what results when adults PKU patients go off low-phenylalanine diet?

eczema & neuronal issues

216

what presents like PKU?

inability to synthesize BioH4

deficiency of dihyropteridine reductase that regenerates reduces BioH4

217

what issue can arise in pregnany PKU patients?

fetal brain damage as excess Phe & metabolites can cross the placenta

218

what is the cause & effect of alkaptonuria?

cause: deficiency of homogentisate oxidase (part of tyrosine catabolism)

effects: black pigment (polymers of homogentisic acid) deposits in cartilage→ causes arthritis in elderly patients

219

cause & effects of hepatorenal tyrosinemia

cause: deficiency of fumarylacetoacetate hydrolase (enzyme of tyrosine catabolism)

effects: severe dz→ liver & kidney failure

common among French Canadians

tx: phe/tyr restriction & inhibitor of p-hydroxyphenylpyruvate oxidase

220

how does folate deficiency affect histidine catabolism?

FIGLU accumulates (histidine metabolite)

 

221

what are the effects of histinemia?

histidine accumulation

no benign phenotype

imidazolepyruvate (transamination product of histidine) interferes w/PKU test giving false +

222

what is the fate of alanine during fasting?

gluconeogenesis in the liver

223

what is the fate of glutamine during fasting?

metabolism in intestine & kidneys

224

what amino acid is required for melanin synthesis?

tyrosine

225

what causes oculocutaneous albinism?

tyrosine deficiency or deficiency of tyrosine transporter in melanosome membrane

226

what is the amino acid source of creatine?

arginine, glycine & S-adensyl-methionine

227

what is the amino acid source of carnitine?

derived from dietary sources (meat) & endogenous synthesis from proetin bound trimethyllysine

228