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Foundations of Medicine > Skildum Week 2 > Flashcards

Skildum Week 2 Flashcards

1
Q

What initial substrates can be used to make acetyl CoA?

A

Glucose - Glycolysis
Fatty Acids - Beta Oxidation
Amino Acids - release nitrogen

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2
Q

What products are formed from the TCA cycle?

A

3 NADH
2 FAD(2H)
1 GTP

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3
Q

Which cells are associated with:
Glut 1 and 3
Glut 2
Glut 4

A

Glut 1 and 3 = most cells (high affinity)
Glut 2 = liver, pancreas (low affinity)
Glut 4 = insulin induced (medium affinity)

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4
Q

How does glucose move during the fasted state?

A

Gluconeogenesis and glucogenolysis in liver cells release glucose that follows concentration gradient out Glut 2 and into Glut1, 3 to myocytes.

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5
Q

What is produced in aerobic and anaerobic glycolysis?

A

aerobic: net 2 ATP 2 NADH and 2 pyruvate
anaerobic: Net 2 ATP, and lactate to regenerate NAD+

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6
Q

Which enzyme catalyzes the first step of glycolysis:

glucose + ATP –> glucose 6-phosphate + ADP

A

hexokinase (most tissues)
glucokinase (in liver)- glucokinase is NOT product inhibited so liver can use glucose as substrate for anabolic reactions when glucose is not needed for energy

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7
Q

Which enzyme catalyzes key regulatory step in glycolysis:

fructose 6-P + ATP –> fructose 1,6 BP + ADP

A

phosphofrucktokinase -1 (PFK-1)

Irreversible reaction

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8
Q

Which enzyme in glycolysis

PEP + ADP –> pyruvate + ATP

A

pyruvate kinase

substrate level phosphorylation makes ATP

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9
Q

What enzyme converts

pyruvate + NADH –> lactate + NAD+

A

lactate dehydrogenase

-recycles NAD+ so glycolysis can continue

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10
Q

What enzyme converts

pyruvate to acetyl CoA to enter the TCA cycle?

A

pyruvate dehydrogenase complex

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11
Q

What is the Cori cycle?

A

Lactate from RBCs enter liver and is converted to glucose by gluconeogenesis.

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12
Q

What is the function of the malate- aspartate shuttle?

A

In cytosol 2 NADH + oxaloacetate –> malate + 2 NAD+
Malate enters mitochondria, in mito:
malate + NAD+ –> oxaloacetate + NADH
Allows NADH to enter the electron transport chain.
Oxaloacetate + amine from glutamate –> aspartate and alpha-ketoglutarate
Aspartate can leave mitochondria (reverted to oxaloacetate again)

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13
Q

Which enzyme in glycolysis produces NADH in the cytosol of heart, liver, and kidney cells?

A

glyceraldehyde 3-phosphate dehydrogenase

NADH must be shuttled to mitochondria by malate-aspartate shuttle

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14
Q

How does reduced NADH equivalents enter electron transport chain in skeletal muscle and brain?

A

glycerol 3-phosphate shuttle.
Dihydroxyacetone-P + NADH –> glycerol 3 phosphate + NAD+
Glycerol 3 phosphate enters inner mito
Glycerol 3 phosphate + FAD –> dihydroxyacetone + FAD2H
the FAD2H enters electron transport chain

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15
Q

Can NADH cross the inner mitochondrial membrane?

A

No, so when it is made in cytosol (glycolysis) must use glycerol 3-phosphate shuttle)

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16
Q

When glycogenolysis is induced, what is pathway for glucose to leave liver cells?

A

glycogen –> glucose 1-P –> glucose 6-P –> glucose (then in other cells first step is hexokinase adding phosphate back)

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17
Q

What allosteric regulation affects phosphofructokinase-1? (Rate limiting step in glycolysis)

A

AMP = allosteric activator
Fructose 1,6-bisphosphate = allosteric activator
ATP = inhibitor
Citrate = inhibitor

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18
Q

What enzyme

2ADP –> AMP + ATP

A

adenylate kinase

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19
Q

What enzyme

fructose 6-phosphate + ATP –> fructose 2,6 BP + ADP

A 
Phosphofruktokinase 2 (PFK2)
shunt off glycolysis
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20
Q

How is the PFK-2 kinase domain activated?

A

Activated by AMP and glucagon to make fructose 2,6BP (activates PFK1)
-also activated by phosphorylation by PKA and AMP-K

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21
Q

How is pyruvate kinase (PK) regulated?

A
  • by concentration substrates and products
  • activated by fructose 1,6-BP
  • inhibited by PKA
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22
Q

Why would increasing PK-M2 (embryonic pyruvate kinase) be favored by cancer cells?

A

PK-M2 binds phosphorylated tyrosines which displaces allosteric activator (fructose 1,6BP) decreasing enzyme activity
-increased rate of glycolysis and block PK = glycolysis intermediates will spill out

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23
Q

How does 2,3-BPG affect red blood cells?

A

When bound it promotes T state of hemoglobin, so promotes releasing bound oxygen to tissues

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24
Q

Why would body increase 2,3-BPG?

A

Response to lack of oxygen
-smokers, high altitude
Activated when electron transport chain is stopped

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25
Q

What is lactic acidosis?

A

When normal ATP oxidation is blocked, glycolysis provides all ATP. To continue, must regenerate NAD+ by making lactate.
-lactate and H+ in blood decreases blood pH

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26
Q

What is ischemia?

A

loss of blood perfusion and oxygen delivery to tissue

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27
Q

What happens when NADH/ NAD+ ratio increases?

A

Product inhibition on pyruvate dehydrogenase

Substrates for lactate dehydrogenase (pyruvate and NADH) favors lactate production

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28
Q

What happens when AMP/ATP ratio increases?

A

-Cell needs more energy to be made
AMP allosterically activates PFK-1
AMP activates AMP-K which activates PFK-2 (which will further activate PFK-1)
Increased rate of glycolysis

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29
Q

What substrates are used for energy when pyruvate dehydrogenase (PDH) is on and off?

A

On- uses carbohydrates

Off- uses fatty acids for energy

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30
Q

Which form of stored energy is most prevalent in the body?

A

triglycerides (fat) > protein > glycogen> glucose

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31
Q

Do saturated or unsaturated fats have a lower melting point?

A

Unsaturated fats since the double bonds lower the melting point (harder to stack)

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32
Q

Which enzyme releases fatty acids from storage?

A

hormone sensitive lipase

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33
Q

How is hormone sensitive lipase regulated?

A

insulin - blocks activity

glucagon, epinephrine, and norepinephrine- activate the enzyme

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34
Q

What transports fatty acids from adipocytes in the blood?

A

serum albumin

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35
Q

What enzyme activates fatty acids in cell cytosol? (these enzymes are specific to FA length)

A

fatty acyl CoA sythetase adds a CoA “handle” to the fatty acid
Reaction requires 2 ATP

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36
Q

Where does beta oxidation of fatty acids take place?

A

In the mitochondrial matrix

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37
Q

How does fatty acyl CoA cross the inner mitochondrial membrane?

A

the carnitine shuttle
carnitine: palmitoyl transferase 1 (CPT1)
carnitine + acyl CoA –> fatty acyl carnitine + CoASH
Passes through carnitine acylcarnitine translocase into inner mito matrix
Carnitine palmitoyl transferase 2 (CPT2):
CoA + fatty acylcarnitine –> fatty acyl CoA + carnitine

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38
Q

What is CPT 2 deficiency and how is it diagnosed?

A

inherited autosomal recessive disorder

Diagnosed by increased fatty acyl carnitine (can’t be reverted to carnitine and fatty acyl CoA)

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39
Q

What are the 4 main steps in fatty acid beta oxidation?

A

Oxidation
Hydration
Oxidation
Carbon-Carbon bond cleavage

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40
Q

What is medium chain acyl CoA dehydrogenase deficiency (MCAD)?

A

acyl CoA dehydrogenase (first oxidation in FA beta oxidation) doesn’t work.
Reye syndrome in infants (fasting hypoketotic anemia,
Diagnosed by high medium chain acyl CoA

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41
Q

What is Jamaican vomiting sickness and what causes it?

A
  • hypoglycin is the poison that inhibits acyl CoA dehydrogenase (like MCAD)
  • from eating unripe ackee fruit
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42
Q

What is the specificity of enoyl CoA hydratase ? (hydration reaction in beta FA oxidation)

A

only accepts substrates with trans double bonds

-if cis, must convert to trans using a reductase that consumes NADPH

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43
Q

How are odd chain length fatty acids oxidized?

A

Thiolase (last step, bond cleavage) splits last 5 into acetyl coA and propionyl CoA.

  • Propionyl CoA to methylmalonyl CoA (by enzyme propionyl CoA carboxylase)
  • methylmalonyl mutase converts to succinyl CoA which enters TCA cycle in the middle
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44
Q

How are very long chain (>22Cs) oxidized in FA beta oxidation?

A

Degraded in peroxisomes, but first step donates electrons to molecular oxygen (and makes H2O2) not FAD
-at 4-6 Cs, go to mitochondria by carnitine based transport

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45
Q

How are branched chain fatty acids broken down? (found in plants)

A

In peroxisomes, make H2O2

-propionyl CoA: enzymes carboxylase, mutase, then succinyl CoA enters TCA cycle

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46
Q

Where does omega- oxidation of fatty acids occur?

A

in the ER by cytochrome P450. Broken down to medium chain length dicarobxyls which can be used by other tissues or excreted in urine

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47
Q

What in body can ONLY use glucose for energy?

A

red blood cells (they have no mitochondria)

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48
Q

What can the brain use for energy?

A

glucose or ketone bodies (cannot use fatty acids)

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49
Q

How is ketone body synthesis regulated?

A

with increase FA beta oxidation in liver, abundant NADH and acetyl CoA which drives TCA cycle backwards (oxaloacetate goes back to malate)

  • Malate leaves for gluconeogenesis
  • reduction in oxaloacetate diverts acetyl CoA into ketone body synthesis (not TCA cycle)
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50
Q

What is ketoacidosis?

A

depression of blood pH by excessive ketone body production

Caused by starvation or diabetes

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51
Q

What substance in inner mitochondrial membrane makes it impermeable?

A

cardiolipin (aggregation of 3 phospholipids)

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52
Q

What is special about mitochondrial DNA?

A
  • circular, reproduces by fission
  • only 13 genes, but has transcriptional machinery
  • hyper mutable
  • more naked (no histones
  • heterogeneous (multiple copies in each mito)
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53
Q

what happens to mito proteins in MERRF (myoclonic epilepsy, muscle tissue has ragged red fibers, progressive dementia)

A

point mutation in mitoDNA makes tRNA for lysine non functional
-mitochondrial proteins with lysine will be truncated

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54
Q

What are the 2 general rules in mitochondrial dysfunction?

A
  • diseases tend to be heterogeneous in severity

- diseases tend to get progressively worse with age

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55
Q

Where are PDH and TCA cycle located?

A

mitochondrial matrix

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56
Q

Which subunits and associated cofactors form pyruvate dehydrogenase (PDH)?

A

E1- pyruvate decarboxylase (TPP)
E2- transacetylase (lipoate)
E3- Dihidrolipoyl dehydrogenase (FAD, NAD+)

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57
Q

PDH is regulated by PDH kinase and PDH phosphatase. What substrates activate and inhibit each?

A

PDH is active when dephosphorylated
PDH Kinase: activated by acetyl CoA and NADH
-inactivated by pyruvate and ADP
PDH phosphatase: activated by Calcium
So PDH is turned on by pyruvate, ADP, and Calcium

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58
Q

In what state (fed or fasted) is PDH turned on?

A

PDH links glycolysis with TCA cycle

-want it on when cell needs energy (high ADP)

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59
Q

What is the key rate limiting step in the TCA cycle?

A

Isocitrate –> alpha ketoglutarate
-enzyme: isocitrate dehydrogenase
Produces NADH and CO2
Large negative delta G

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60
Q

How is isocitrate dehydrogenase (key TCA cycle step) regulated?

A

ADP lowers Km (making the enzyme more active)

61
Q

When TCA cycle is stopped, which substrates convert back to previous step?

A

Isocitrate to citrate

oxaloacetate to malate

62
Q

How is HIF 1 alpha oxygen sensor linked to the TCA cycle?

A

HIF 1 alpha is normally hydroxylated and ubiquinated in normal oxygen conditions.
Fumarate will compete with enzyme (prolyl hydroxylase) when it spills from TCA cycle
-without hydroxylation, HIF becomes transcription factor- can cause tumors

63
Q

How is the TCA cycle regulated?

A

turned on by increased NAD+/ NADH

enzymes turn off by buildup or by regulation

64
Q

What are the anabolic functions of the TCA cycle?

A 
oxaloacetate - amino acid biosynthesis
malate - glucose (gluconeogenesis)
succinyl CoA- heme biosynthesis
alpha ketoglutarate - glutamine - GABA
Citrate - fatty acid biosynthesis
65
Q

What enzyme converts pyruvate to oxaloacetate?

A

pyruvate carboxylase (using biotin as a cofactor)

66
Q

Which enzyme takes 2 ADP after muscle contractions to form ATP and AMP

A

adenylate kinase

67
Q

the condition myoadenylate deaminase deficiency is caused by…
and causes…

A

inherited mutations in gene coding muscle specific AMPD1 (AMP deaminase- converts AMP to NH4+ and IMP. IMP goes back to TCA eventually)
-causes long term muscle break down, muscle pain and weakness
Diagnosed: no increase in blood NH4+ after exercising

68
Q

What is complex 1 in electron transport chain?

A

NADH dehydrogenase. transports 4 protons into intermembrane space.
Iron sulfur centers pass electrons to CoQ

69
Q

What is complex 2 in electron transport chain?

A

succinate dehydrogenase (reduces succinate to fumarate while making FAD2H)

  • enzyme is part of TCA cycle
  • does not cross inner mito membrane
70
Q

what does pyruvate carboxylase do?

A

Converts pyruvate to oxaloacetate (cofactor is biotin)

71
Q

What is complex 3 in electron transport chain?

A

cytochrome b-c complex.

pumps 4 protons into intermembrane space

72
Q

What is complex 4 in electron transport chain?

A

cytochrome c oxidase, takes O2 and makes water

-puts 2 protons into intermembrane space

73
Q

How does proton gradient make ATP?

A

APT synthase. translocation of 12 carbons completes 1 turn, makes 3 ATP per turn

74
Q

What is uncoupling?

A

transfer of electrons from NADH to oxygen without generating ATP

75
Q

What is adaptive thermogenesis?

A

norepinephrine released when cold
NE activates a lipase which forms free FAs from triacylglycerol
-thermogenin (UCP1) is a proton channel activate to bypass ATP synthase
-make heat without work

76
Q

What is chemical uncoupling?

A

lipid soluble molecules with pKa near neutral can bind protons, diffuse membrane, and release protons in matrix
ex) Dinitrophenol, and salicylate

77
Q

What is mechanical uncoupling?

A

damage on membrane from ROS or mito swelling lets protons leak through membrane

78
Q

What is the inner mitochondrial membrane permeable to?

A

O2, CO2, NH3, H2O

79
Q

What are the 3 basic types of transport systems?

A

Antiporters transport one molecule in and another molecule out.
ATP / ADP
Symporters transport two molecules in or out.
pyruvate + H+, Pi + H+
Uniporters transport one molecule in or out.
calcium

80
Q

Why does PDH deficiency have mainly neural effects?

A

the brain needs ketone bodies to function without glucose, and without PDH pyruvate doesn’t become acetyl CoA

81
Q

Leigh’s disease affects the E1 subunit of PDH. How can this be remedied?

A

Thiamine (B1) becomes TPP, the carboxylase cofactor associated with E1

82
Q

What are fatty acids used for in the body?

A
  • membranes

- for energy, store FAs as fat

83
Q

When and where are fatty acids made?

A

synthesized from acetyl CoA in liver cells whenever ingested calories exceed energy need
-with excess energy isocitrate dehydrogenase is inhibited, so drives citrate toward FA synthesis

84
Q

How is citrate involved in FA synthesis?

A

oxaloacete + acetyl CoA –> CoASH + citrate. Citrate can leave mitochondria for cytosol
In cytosol: acetyl CoA is reformed (oxaloacetate is converted to malate then pyruvate)

85
Q

Which enzyme converts oxaloacetate to malate?

A

malate dehydrogenase, also makes NAD+

86
Q

Which enzyme converts malate to pyruvate while generating NADPH?

A 
malate decarboxylase (malic enzyme)
-NADPH is used by fatty acid synthase (FAS)
87
Q

What is the importance of the pyruvate/ malate cycle in lipogenesis?

A
  • transports acetyl CoA from mitochondria to cytosol

- malic enzyme generates NADPH to power fatty acid sythesis

88
Q

Which enzyme in fatty acid synthesis converts acetyl CoA to malonyl CoA?

A

acetyl CoA carboxylase (ACC)

  • requires energy (ATP)
  • cofactor is biotin
  • rate limiting step in FA synthesis
89
Q

What are the 4 main steps in FA synthesis?

A

Bond formation
Reduction
Dehydration
Reduction

90
Q

Compare and contrast FA beta oxidation and FA synthesis

A

Same: 2 carbons at a time
Different: beta oxidation in mitochondria and FA synthesis in cytoplasm
-beta oxidation with multiple enzymes and FA synthesis just 1

91
Q

What are the 2 sulfur groups on fatty acid synthase (FAS)?

A

phosphopantetheinyl group sulfur

sulfur from cysteine side chain

92
Q

Where does FA synthesis elongation occur?

A

Endoplasmic reticulum

93
Q

What are the constraints for making unsaturated FAs?

A

Can’t add within 9 carbons from omega end

ex: need dietary sources of linoleic and linolenic

94
Q

What is used as the backbone for FAs?

A

glycerol 3-phosphate

95
Q

What components make up a triglyceride?

A

3 molecules fatty acyl CoA, 1 glycerol 3 phosphate

96
Q

Where is glycerol kinase found in the body?

A

Only the liver, in other tissues glycerol 3 phosphate is only made during glycolysis (liver can make more)

97
Q

how is phosphotidylcholine made?

A

choline + CTP makes CDP-choline

diacylglycerol + CDP-choline –> phosphatidylcholine

98
Q

How is cardiolipin made?

A

by linking phosphatidyl glycerol (glycerophosphate with glycerol head group) with CDP diacylglycerol

99
Q

What are ether glycerolipids (plasmalogens) and how are they formed?

A

have ether linkage on 1 carbon of glycerol backbone

-special roles in specific fibers (myelin sheath)

100
Q

What backbone do sphingolipids have?

A

ceramide (not glycerol). ceramide is derived from serine and palmitoyl CoA

101
Q

What makes sphingomyelin?

A

ceramide and choline

102
Q

What makes cerebroside?

A

ceramide and glucose

103
Q

What is dipalmitoylphosphatidylcholine?

A

Major component in lung surfactant.

  • measured in amniotic fluid to see dev. stage
  • ratio with sphingomyelin- when more phosphatidylcholine, closer to birth
104
Q

What is leptin?

A

hormone that indicates satiety. Levels increase when TAGs are high
-acts in hypothalamus

105
Q

What is used as the backbone for FAs?

A

glycerol 3-phosphate

106
Q

What components make up a triglyceride?

A

3 molecules fatty acyl CoA, 1 glycerol 3 phosphate

107
Q

Where is glycerol kinase found in the body?

A

Only the liver, in other tissues glycerol 3 phosphate is only made during glycolysis (liver can make more)

108
Q

how is phosphotidylcholine made?

A

choline + CTP makes CDP-choline

diacylglycerol + CDP-choline –> phosphatidylcholine

109
Q

How is cardiolipin made?

A

by linking phosphatidyl glycerol (glycerophosphate with glycerol head group) with CDP diacylglycerol

110
Q

What are ether glycerolipids (plasmalogens) and how are they formed?

A

have ether linkage on 1 carbon of glycerol backbone

-special roles in specific fibers (myelin sheath)

111
Q

What backbone do sphingolipids have?

A

ceramide (not glycerol). ceramide is derived from serine and palmitoyl CoA

112
Q

What makes sphingomyelin?

A

ceramide and choline

113
Q

What makes cerebroside?

A

ceramide and glucose

114
Q

What is dipalmitoylphosphatidylcholine?

A

Major component in lung surfactant.

  • measured in amniotic fluid to see dev. stage
  • ratio with sphingomyelin- when more phosphatidylcholine, closer to birth
115
Q

What is leptin?

A

hormone that indicates satiety. Levels increase when TAGs are high

116
Q

What is adiponectin?

A

hormone, leads to suppression of FA synthesis and increased FA oxidation

  • decreased in obesity
  • stops FA CoA carboxylase
117
Q

What is Kwarshiorkor?

A

a negative net nitrogen balance (healthy adults excrete as much nitrogen as they consume in 24 hours, children have a positive nitrogen balance)

118
Q

How are amino acids from the blood utilized?

A
  • make proteins
  • form nitrogen containing compounds
  • spit into carbon for energy and nitrogen goes to urea cycle for excretion
119
Q

What are the symptoms of ammonia toxicity?

A

neuronal cells are most vulnerable, lethargy, headache, seizures, etc

120
Q 
What are the corresponding alpha keto acids of:
glutamate
aspartate
alanine
glutamine
A

glutamate - alpha ketoglutarate
aspartate - oxaloacetate
alanine - pyruvate
glutamine - glutamate

121
Q

Why is arginine important in the urea cycle?

A
  • activates synthesis of NAG which activates carbamoyl phosphate sunthetase (CPS 1)
  • converted to ornithine and urea by arginase
122
Q

Which enzyme performs the aminotransferase reaction to convert alpha ketoglutarate to glutamate?

A

glutamate dehydrogenase

123
Q

What are the 2 sources of nitrogen in the body?

A
  • from deamination of amino acids (glutamate dehydrogenase)

- from transamination of amino acids (glutamate transferase)

124
Q

How does the body cope with long term high nitrogen?

A
  • glutamine increases the transcription of arginosuccinate synthase (in urea cycle converts aspartate to arginosuccinate)
  • long term adaptations to excess protein breakdown (high protein diet, starvation)
125
Q

What does elevated urinary orotic acid indicate?

A
  • it’s a characteristic of a urea cycle inherited disorder downstream of CPS-1
  • ex) high urinary orotic acid when ornithine transcarbamoylase is non-functioning
  • inactive arginase (in cytosol) only moderately elevates urinary orotic acid
126
Q

How does nitrogen enter the urea cycle?

A
  • free ammonium

- aspartate

127
Q

What causes HHH syndrome?

A

HHH = hyperammonaemia, hyperornithaemia, and homocitruillinaemia,
-inherited defect in ornithine/ citrulline antiporter

128
Q

How do you treat inherited disorders in urea cycle?

A

Goal is to decrease blood NH4+

  • low protein diet
  • N-carbamoylglutamic acid (drug that mimics NAG which activates CPS1)
  • eliminate nitrogen in alternative pathways (arginine, benzoic acid, phenylbutyrate)
  • liver transplant/ hepatocyte transfusion
  • viral transduced gene therapy
129
Q

What are the 3 cofactors for enzymes in amino acid metabolism?

A

PLP (transaminations, deaminations, carbon chain transfers)
Tetrahydrofolate, FH4 (one carbon transfers)
Tetrahydrobiopterin, BH4 (ring hydroxylations)

130
Q

How many essential and non-essential amino acids are there?

A
  • 11 non-essential (made using carbon from glucose and nitrogen from other AAs)
  • 9 essential (required in diet. (arginine is essential only for children, not adults)
131
Q

What are the essential amino acids?

A

M.V. Pitthall
(Methionine, Valine, Phenyalanine, Isoleucine, Tryptophan, Threonine, Histidine, Arginine, Leucine, Lysine)
-arginine is not essential for adults

132
Q

How is tyrosine made?

A

add OH to para ring position on phenylalanine (without phenylalanine, tyrosine must be eaten)
-uses tetrahydrobiopterin with enzyme phenylalanine hydroxylase

133
Q

How is cysteine made?

A

uses methionine as precursor

-both have sulfur groups

134
Q

Which amino acids can be synthesized from glycolytic intermediates? (mainly 3-phosphoglycerate)

A

glycine, serine, cysteine, alanine

135
Q

What substrates are combined to form cysteine?

A

serine and a sulfur from homocysteine

136
Q

What does degradation of cysteine make?

A

Either:

  • sulfuric acid (acidifies urine)
  • PAPS (an activated sulfate for use in other reactions)
137
Q

What is cystinuria and what does it cause?

A
  • inherited mutation (autosomal recessive) in AA carrier for cysteine and basic amino acids (lysine, arginine, and ornithine)
  • cysteine precipitates causing kidney stones
138
Q

What enzyme coverts alanine to pyruvate? and what is accepts the amino group?

A 
alanine aminotransferase (ALT) and alpha ketoglutarate accepts the nitrogen to become glutamate
-ALT is normally only found in the liver
139
Q

What enzyme converts oxaloacetate to aspartate? what cofactor?

A
  • AST (aspartate aminotransferase)

- cofactor= PLP

140
Q

What is the major transporter of nitrogen in the blood?

A

glutamine

-glutamine synthetase adds a free nitrogen to glutamate

141
Q

What is Maple Syrup Urine Disease?

A

Autosomal recessive deficiency in branched chain alpha-keto acid dehydrogenase

  • elevated plasma and urine Val, Iso, Leu, and keto acids
  • fatal when untreated
142
Q

Why does a high dose of thiamine help Maple Syrup Urine Disease?

A

the enzyme branched chain alpha-keto acid dehydrogenase is like PDH- first subunit decarboxylates with TPP

143
Q

What 2 substrates can phenylalanine and tyrosine be degraded into?

A

fumarate and acetoacetate

144
Q

What is PKU and what enzyme is affected?

A

Defect in converting phenylalanine to tyrosine

  • problem with phenylalanine hydroxylase
  • phenylalanine builds up in brain and blood
145
Q

A defect in which enzyme can appear to be PKU?

A

problem with dihydropteridine reductase (converts quinonoid kihydrobiopterin BH2 back into tetrahydrobiopterin BH4)
-without BH4, phenylalanine hydroxylase will not function

146
Q

A defect in which enzyme causes Tyrosinemia (type 2)? and what are the symptoms?

A
  • enzyme tyrosine aminotransferase

- plaques develop on feet and hands, corneal ulcers, mental retardation

147
Q

What is alcaptonuria?

A

Rare autosomal recessive deficiency in enzyme homogentisate oxidase (in Phe degradation)

  • homogentisate accumulates and is excreted in urine giving it a dark color
  • not fatal
148
Q

A defect in which enzyme causes Tyrosinema (Type 1)? and what are symtoms? Treatment?

A
  • fumaryloacetoacetate hydrolase (FAH)
  • results in accumulation of succinylacetone
  • acute hepatic crisis, jaundice, hepatomegaly, elevated AST and ALT, hypoglycemia
  • treated with Nitrosinone

Foundations of Medicine (7 decks)

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