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Biochemistry > First Pass Miss Exam 2 > Flashcards

First Pass Miss Exam 2 Flashcards

1
Q

What is the function of cholesterol in the Lo phase?

A

Lamellar Liquid Ordered Phase
Blocks free rotation around C-C bonds in Lalpha (liquid crystalline)
Blocks van der Waals in Lbeta (gel)

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2
Q

What is the function of the citrate shuttle?

A

Move acetyl-CoA produced in mitochondria to the cytosol

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3
Q

What enzyme is the opposite function of citrate synthase in the citrate shuttle?

A

ATP citrate lyase - forms OAA

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4
Q

How does the citrate shuttle produce NADPH?

A

via malic enzyme in the cytosol, oxidizes and decarboxylates malate to pyruvate, forming NADPH + CO2

Produces 8/14 NAPH for FAS

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5
Q

What are the two allosteric effectors of Acetyl-CoA carboxylase?

A

positive - Citrate (build fats, high energy charge)

negative - palmitate (enough fats, stop building)

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6
Q

What controls phosphorylation of Acetyl-CoA carboxylase?

A

+ - insulin
- glucagon, epinephrine, and palmitate which activates AMPK.

Phosphorylation promotes the non-filamentous form which is inactive

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7
Q

What enzyme is a drug target for obesity in fatty acid acyl-transfers?

A

DAG acyltransferase.

Catalyzes 2,3-DAG to TAG, which allows hepatocytes and enterocytes to mobilize fatty acids into chylomicrons / VLDL

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8
Q

How is propionyl-CoA converted to succinyl-CoA?

A

It is carboxylated to methylmalonyl-CoA (requires B7), which is epimerized to the L-isomer, and mutated to succinyl-CoA (requires adoB12)

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9
Q

What enzyme is missing in liver which prevents it from using ketone bodies for energy?

A

Succinyl-Coa:acetoacetate CoA transferase. Makes acetoacetate into acetoacetyl-CoA which is cleaved by beta-thiolase / acetyl-CoA acetyltransferase to 2 acetyl-CoA.

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10
Q

What is the most common FA defect and what does it metabolically cause?

A

MCAD deficiency. Causes secondary carnitine deficiency. Omega-oxidation occurs which causes dicarboxylic fatty acids and thus metabolic acidosis.

Buildup of octanoic acid (8C) leads to hyperammonemia + mitochondrial damage

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11
Q

What is x-linked adrenoleukodystrophy?

A

Defected ABCD1 gene which encodes peroxisomal VLCFA transporter, causes accumulation of VLCFA’s which cause CNS and adrenal problems.

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12
Q

What is Zellweger Syndrome / Refsum disease

A

Autosomal recess disease which prevents normal peroxisome biogenesis, accumulates branched chain fatty acids and causes deafness + blindness. It’s effects also cause X-ALD symptoms.

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13
Q

What is a common branched chain fatty acid?

A

Phytanic acid

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14
Q

Why is phospholipase A2 (PLA2) important in eicosanoid metabolism?

A

Typically C2 carries the unsaturated fatty acid, and arachidonic acid is an eicosinoid which is a 4 u.u. PUFA.

C1 carries a fully saturated FA

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15
Q

What is the name of the surfactant?

A

DPPC - dipalmitoylphosphotidylcholine

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16
Q

What is the primary difference between plasmalogens and phosphoglycerols, and what are two common headgroups?

A

ether rather than ester bond, and there can be an alkene paired with ether

Head groups: choline + ethanolamine

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17
Q

What are the two pathways which activate phosphatidate with CTP, rather than the headgroup?

A

Cardiolipin (uses phosphoglycerol head group)

Phosphotidylinositol (uses inositol head group)

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18
Q

If activating the head group first, how is the phosphatidate prepared to accept the CDP-R group?

A

phosphatidate phosphatase is used to form DAG, before i.e. CDP-choline is added

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19
Q

HOw is phosphatidylserine produced?

A

serine / ethanolamine are exchanged in transfer reaction between serine / phosphatidylethanolamine.

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20
Q

What is sphingosine?

A

Serine backbone + palmitate at C1 (C1 = carbon nearest the nitrogen)

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21
Q

What is ceramide?

A

Sphingosine + N-acyl FA at serine nitrogen (C2 is still open)

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22
Q

What is sphingomyelin?

A

Phosphocholine at C2

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23
Q

What are cerebrosides and what is its main subclass?

A

Glycosphingolipid with monosaccharide (glucose / galactose)
Cerebro = only 1
Main subclass: Sulfatide - sulfated galactocerebroside

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24
Q

What are globosides and what are they called when you add NAN sugars?

A

global = many. Polysaccharide side chains on glycosphingolipids.

Gangliosides - there are many negative charged ganglia in the brain. Have nomenclature for (# nan sugars M,D,T, core sugar sequence)

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25
Q

How are gangliosides formed from ceramide?

A

Ceramide has sugars added via UDP activation, then NAN branches sugars from CMP activation.

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26
Q

How is mevalonate formed?

A

Rate-limiting, irreversible first step of cholesterol synthesis.

HMG-CoA Reductase uses 2 NADPH to convert HMG-CoA to mevalonate

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27
Q

What is the purpose of the trans-methylgluconate shunt?

A

Can convert isopentenyl-PP to HMG CoA and return carbons back to acetyl-CoA if need be

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28
Q

What form of cholesterol can cross the blood-brain-barrier?

A

Oxysterols which are hydroxylated forms of cholesterol producted by Cytochrome P450

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29
Q

How do you remember the squalene to cholesterol synthesis pathway?

A

forms Squalene oxide first (30C)

then, LZD (sounds like LSD)
Lanosterol
Zymosterol
Desmosterol ->

7-DHC -> cholesterol

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30
Q

What are the three actions of the liver X receptors, and what do they respond to? Where are they found?

A

Respond to increasing concentration of oxysterols, found in hepatocytes

  1. Downregulates SREBPs
  2. Induces HDL transporters (lower free cholesterol via efflux)
  3. Stimulate FA synthesis to provide substrate for cholesterol esterification (lowers free concentration)
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31
Q

What is the primary regulator control on HMG-CoA reductase?

A

Phosphorylation inactivates it - (AMPK under control of glucagon / epi)

Dephosphorylation activates it (PP2A - insulin)

Low cell ATP also stimulates AMPK which turns off HMG-CoA and thus cholesterol synthesis

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32
Q

How do statins work?

A

Reversible competitive inhibitors of HMG-CoA reductase

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33
Q

What must occur to form a bile salt from cholesterol? What are they complex with?

A

7-alpha hydroxylation + 12-alpha hydroxylation + flipping of 3-alpha hydroxylation stereochemistry and loss of three terminal carbons (makes it 24 carbon instead of 27)

Then complex with glycine or taurine (3:1 ratio, respectively)

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34
Q

What occurs to form secondary bile salts from primary bile salts?

A

Bacterial conversion in liver, removes 7, 12 alpha hydroxyls + conjugated amino acid

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35
Q

What is the first major step of hormone synthesis from cholesterol?

A

Cleave 6 carbons off to become only 21 carbon Pregnenole.

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36
Q

Where do most reactions occur in hormone synthesis, and which enzymes are not included in this?

A

Most occur in smooth ER, a few happen in the mitochondria

  1. Cholesterol side chain cleavage enzyme (-6 C)
  2. Aldosterone synthase
  3. 11-beta hydroxylase

Last two are only involved in glucocorticoid / mineralocorticoid synthesis

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37
Q

What conversions occur to go from progesterone to testosterone / estrogen, broadly?

A

Progesterone -> testosterone = cleave 2 carbon ketone group off at position 17 (now 19-C)

Testosterone -> estrogen - aromatize the first six-carbonyl ring with hydroxyl at C3 remove methyl at position 10 (now 18-C)

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38
Q

What is the apo-protein of nascent chylomicrons?

A

Apo B-48

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39
Q

What two apoproteins are donated by HDL to mature chylomicrons?

A

Apo CII and Apo E

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40
Q

How do chylomicron remnants bind in liver?

A

LDL receptor, via apoE. The ApoCII is no longer present because it was donated back to HDL

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41
Q

What are the apoproteins of mature vs nascent VLDL?

A

nascent: Apo B-100
Mature: B100, E, CII (latter two from HDL)

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42
Q

How is LDL formed from VLDL?

A

Becomes IDL as it loses Apo CII and E, only again having B100 but lost all of its TAGs and increased its cholesterol concentration.

Now binds LDL on periphery or via its B100 as ligand on LDLR in liver

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43
Q

What are the apoproteins of the nascent HDL?

A

Apo A-I, Apo-CII, Apo-E

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44
Q

How does HDL uptake cholesterol from tissues and hold it?

A

uses ABCA1 transporter to take up free cholesterol

Free cholesterol turned into cholesterol ester by converting phosphatidylcholine to lyso-PC (lost a FA). Uses PCAT (phosphatidylcholine acyltransferase)

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45
Q

What is the function of CETP?

A

Cholesterol ester transfer protein, transfers cholesterol esters from HDL2 to VLDL, and TAGS to VLDL to HDL. This makes the VLDL have a higher [cholesterol] to become LDL.

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46
Q

What are the two types of scavenger receptors we care about?

A
  1. SR-B1 - binds HDL in liver cells

2. SR-CD36 - binds mLDL (oxidized) in macrophages

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47
Q

Why are HDLs good aside from cholesterol removal, and why do women have more?

A

Estrogens increase HDL levels

  1. Increases production of NO - anti-inflammatory
  2. Free radical scavenging
  3. Promote integrity of endothelial layer, as well as preventing cell adhesion, aggregation / thrombosis
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48
Q

What does C-reactive protein measure?

A

It is produced in vascular smooth muscle cells / endothelium + liver in response to pro-inflammatory cytokines.

Measures levels of low-grade inflammation, considered an “acute phase protein”

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49
Q

What amino acids are the main blood carriers of nitrogen and what do they ultimately funnel into?

A

Glutamine, alanine

Funnel into: Glutamate

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50
Q

What are the two opposing factors in glutamate dehydrogenase and what regulates them?

A

Catabolic: form NADH by deaminating glutamate to aKG
Anabolic: Use NADPH to reduce imine group of a-KG to Glu intermediate to form aKG

Anabolic: Upregulated with ATP/GTP binding
Catabolic: Upregulated with ADP/GDP binding

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51
Q

What cofactor do transaminations use, and what type of reaction is it?

A

Vitamin B6: Pyridoxal-6-P. Forms a Schiff base holds NH3 as pyridoxamine and donates to next incoming AA, re-binding to lysine

Reaction type: “Ping pong” reaction

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52
Q

What reactants are common to all transaminases?

A

All typically use Glu / a-KG as one of the pairs.

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53
Q

What are the two most important transaminases?

A

Alanine / Aspartate (ALT / AST), common markers of tissue damage

Alanine -> transport NH3 in blood
Aspartate -> give NH3 in urea cycle

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54
Q

What enzyme forms glutamine from glutamate?

A

Glutamine synthetase -> uses ATP + Glu

55
Q

Where is glutaminase most active and why?

A

In the mitochondria, where the urea cycle begins. Important for liver /kidney clearance of NH3, plus neurotransmitters in brain.

Converts Gln to Glu + NH3.

56
Q

What is the function of glutamate / glutamine in astrocytes?

A

Glutamate is taken up in synaptic cleft and stored as glutamine which is nontoxic. Excess glutamate can be deaminated as well and aKG can be used for energy.

Glutamine is returned to pre-synaptic neuron which deaminates it to glutamate and stores in vesicles until next synapse.

57
Q

At what stage in the urea cycle is urea actually formed? What happens to its product?

A

Cleavage of arginine to ornithine.

Ornithine is converted to citrulline in mitochondria via ornithine transcarbamoylase (OTCase)

58
Q

What is the function of N-acetylglutamate synthase (NAGS) and what activates it?

A

Forms N-acetylglutamate from glutamate + acetyl-CoA

Activated by arginine

59
Q

What does N-acetylglutamate do? What happens when you’re NAGS deficient?

A

activates CPSI to work faster, under conditions of high protein diet, or when protein is being broken down for energy

NAGS deficiency - closely resembles CPS1 deficiency

60
Q

What is the clinical presentation of OTCase deficiency and what is its inheritance pattern?

A

Buildup of carbamoyl phosphate leads to flooded pyrimidine biosynthesis -> orotic aciduria

X-linked DOMINANT

61
Q

What is ORNT1 deficiency? What is its presentation?

A

Lack of ornithine / citrulline antiporter, such that ornithine cannot enter mitochondria

OTCase will carbamoylate lysine to homocitrulline instead

Triple H: Hyperornithinemia, Hyperammonemia, homocitrullinemia

62
Q

What are the manifestations of hyperammonemia?

A

serious deficit of aKG, all carbons funneled towards Gln which causes edema + reduction in neutotransmitters. Oxphos can be disrupted as ammonia disrupts proton gradients

63
Q

What are the treatments for hyperammonemia?

A
  1. Hemodialysis
  2. IV nitrogen scavengers such as: phenylbutyrate or benzoate which react to form CoA esters in body and scavenge nitrogen groups from glutamine / glycine respectively
64
Q

What are the two strictly ketogenic substrates?

A

Leucine / Lysine

65
Q

What defines a gluconeogenic substrate?

A

Can form DHAP or GA3P in just one turn of a metabolic pathway

66
Q

What is the function of B12 in the production of methionine? Why does this require B9?

A

Transfers methyl group to converts homocysteine to methionine via methionine synthase

B9 (N5-methyl-THF) is required to convert B12 to meB12 in the reaction of methionine synthase

67
Q

What does the enzyme MAT do?

A

Methionine adenosyltransferase

Transfers adenosyl group to methionine, forminine S-adenosyl methionine (SAM)

68
Q

What is the function of SAM and what is it converted to?

A

SAM donates the CH3 of methionine (which was added by methionine synthase) to form S-adenosyl homocysteine (SAH)

It is involved in many methyl transfer reactions, such as formation of epinephrine from norepinephrine (nor = no methyl!), creatine, methylated nucleotides, phosphatidylcholine (from PE), melatonin

69
Q

What does serine dehydratase do? What enzyme is similar?

A

NH3 + pyruvate

Threonine dehydratase also yields NH3

70
Q

Why is the conversion of serine to glycine important for B9?

A

Forms 5,10-me-THF, via serine hydroxymethyltransferase (SHMT)

71
Q

Can glycine alone convert THF to 5,10-me-THF?

A

Yes, via a glycine cleavage system, dependent on B6

72
Q

How is 5-me-THF formed (needed to form methionine from homocysteine via methionine synthase) from 5,10-me-THF?

A

methylene tetrahydrofolate reductatse (MTHFR)

73
Q

Why is cysteine synthesis dependent on B6?

A

Cystathionine intermediate requires B6 to be synthesized. Basically add serine to transfer the methyl from homocysteine to serine, forming cysteine.

74
Q

What does buildup of homocysteine cause, and what causes it to appear in blood vs appear in urine?

A

Causes higher incidence of heart attacks / strokes

Urine: Cystathionine synthase is deficient, so homocysteine builds up

Blood: Due to B9/B12 deficiency, so methionine cannot be regenerated from homocysteine and it builds up

75
Q

Where are branched chain amino acids broken down? What is the most important enzyme of the pathway?

A

Val, leu, ile, all broken down elsewhere in the body as fuel. CANNOT BE BROKEN DOWN IN LIVER

After the amino acid is deaminated, its alpha-ketoacid is decarboxylated and thioesterified to CoA via branched chain a-ketoacid dehydrogenase (uses B1)

These thioesters are converted into products via acyl-CoA dehydrogenases on ETC (FAD cofactor)

76
Q

What happens to valine, leucine, and isoleucine

A

Valine - glucogenic - forms propionyl-CoA
Leucine - ketogenic - forms acetoacetate and acetyl-COA
Isoleucine - forms both, via propionyl-CoA and acetyl-CoA

77
Q

What causes maple syrup urine disease (MSUD)

A

BCAKADH deficiency -> BCAA’s accumulate. Sotolon is the breakdown metabolite of Ile metabolism that is smelled.

Manifestations: hyperammonia, acidosis, death before year 1. Difficult to manage because BCAA’s are essential

78
Q

What enzyme is messed up in phenylketonuria?

A

Phenylalanine hydroxylase, converts Phe to Tyr in 1:3, since enzyme required to synthesize BH4 cofactor is messed up.

79
Q

What are the two nonessential amino acids which are strangely grouped?

A

Cysteine (since sulfur is gained from essential Met)

Tyrosine (entirely dependent on essential Phe)

80
Q

How is proline synthesized?

A

From glutamate, via semialdehyde intermediate

81
Q

How is serine synthesized?

A

from 3-phosphoglycerate

82
Q

How is GABA formed?

A

Decarboxylation of glutamate

83
Q

How is histamine formed?

A

Decarboxylation of histamine

84
Q

What does tyrosine form when it is oxidized / decarboxylated?

A

Catecholamines

85
Q

What do glycine + arginine combine to form?

A

Creatine, with ornithine being lost and an intermediate which needs to be methylated by S-adenosylmethionine

86
Q

How is serotonin formed?

A

Oxidation and decarboxylation of tryptophan

87
Q

How is NO formed?

A

Oxidation of arginine with loss of citrulline

88
Q

What is the most abundant protein in blood?

A

albumin

89
Q

Why is prothrombin time a good way to assess liver function?

A

Liver produces coagulation factors 2, 7, 9, and 10 via gamma-glutamyl modification for Ca+2 binding. (vitamin K dependent)

90
Q

What is ceruloplasmin, and what is its deficiency called? How is this related to copper?

A

Protein which is required to oxidize iron in order to solubilize it to form RBCs, has a Cu cofactor.

Ceruloplasmin deficiency = Wilson’s disease
Anemia can be caused by lack of copper

91
Q

What is the first step of heme synthesis? what is it inhibited by?

A

Formation of ALA via ALA synthesis, starting with succinyl-CoA and glycine

92
Q

What ultimately happens in heme synthesis?

A

Half in cytosol, half in mitochondria, 4 porphobilinogen (PBG)’s are put together and ultimately form heme

93
Q

What are the two catabolic steps formng bilirubin from heme?

A

Heme converted to biliverdin via heme oxygenase

Biliverdin converted to bilirubin via biliverdin reductase

94
Q

What must bilirubin be conjugated with before it is excreted into bile / urine? What carries unconjugated bilirubin?

A

Glucuronic acid. Unconjugated bilirubin is carried by albumin. Bilirubin is the primary reason for dark feces.

95
Q

What is the function of NADPH-dependent cytochrome P450 in alcohol metabolism?

A

replaces alcohol dehydrogenase in cytoplasm to form aldehyde, forming superoxide radicals using oxygen to accept electrons rather than NAD+. Can lead to cirrhosis

96
Q

What are the main metabolic conditions associated with fatty liver (hepatic steatosis) from alcoholism?

A

Hypoglycemia (all pyruvate is pushed to lactate), hyperlipidemia (all DHAP is pushed to glycerol-3-P, and acetates converted to acetyl-CoA), lactic acidosis (all pyruvate pushed to lactate, high NADH/NAD+ ratio)

97
Q

What is the general scheme for metabolism of drugs by liver?

A
  1. Increase polarity of drug via oxidation / hydroxylation by P450 oxidases
  2. Conjugate with glucuronide / sulfate
98
Q

What are the 3 most important cytochrome P450s in drug metabolism? Which gene is most involved?

A

CYP1, CYP2, CYP3

CYP3A4 = gene most involved

99
Q

What type of enzymes are cytochrome P450s?

A

Oxygenases with an Fe+3 cofactor. Ultimately oxidize NADPH as well as the drug, while throwing two electrons towards water.

100
Q

Why is tylenol toxic at high concentrations? What is the antidote?

A

At too high of doses, it can no longer be conjugated, and is instead oxidized by CYP450s, which makes NABQI, a toxic compound causing free-radical peroxidation of membrane lipids in liver

Antidote: N-acetylcysteine

101
Q

What are the four most common liver enzymes tested to assess liver function?

A

Gamma-glutamyl transferase, AST / ALT, and alkaline phosphatase (ALP)

102
Q

In what type of jaundice to stools appear pale?

A

Post-hepatic, since it is an obstruction of biliary drainage. There will be an increased conjugated fraction of bilirubin in plasma, urine is primary excretion method

103
Q

What is kernicterus?

A

A complication of neonatal jaundice, where unconjugated bilirubin has crossed the blood brain barrier and caused CNS damage. In adults, this cannot happen because BBB is more developed

104
Q

What are treatments for neonatal jaundice?

A
  1. Phototherapy with blue/white light - breaks bilirubin to pigments beware of B2 deficiency
  2. blood transfusion / exchange
105
Q

What nucleotide are all purines channels through? All pyrimidines?

A

Purines: IMP
Pyrimidines: OMP

106
Q

Where do the atoms in the purine ring come from?

A

carbons: 2x glycine, 2x 10-formyl THF, 1x CO2.
Nitrogens: 1x glycine, 1x aspartate, 2x glutamine

1x glycine backbone + 2 carbons from THF + 1 from CO2 + 1 nitrogen from ASP + 2 nitrogens from glutamine

107
Q

Where do the atoms in the pyrimidine ring come from?

A

Carbons: 3x aspartate, 1x HCO3
Nitrogens: 1x aspartate, 1x glutamine

so 1x aspartate backbone + 1x HCO3 + 1x glutamine nitrogen = 6 total

108
Q

What is the committed step of purine synthesis? what is its regulation?

A

Glutamine-PRPP amidotransferase, adds NH2 of glutamine to PRPP at 1 position (where pyrophosphate was).

Ultimately leads to IMP. Inhibited by ATP/GTP in all forms

109
Q

How does IMP become AMP? what is its regulation?

A

Ketone is converted to amine, with adenylosuccinate intermediate (turns aspartate into fumurate, aspartate is the nitrogen donor)

Inhibited by AMP, activated by all GTPs

110
Q

How does IMP become GMP? what is its regulation?

A

NH2 is added on C2. Nitrogen comes from Gln, uses H20 to add a hydroxyl, then reduces to a ketone, creating NADH (XMP intermediate) and converts to amine using ATP

Inhibited by GMP, activated by all ATPs

111
Q

What do phosphoribosyl-transferases do?

A

They are in the base salvage pathways, that can take the bases and add them to the 1’ pyrophosphate of PRPP and form AMP bases.

112
Q

What causes Lesch-Nyman Syndrome? What is it marked by?

A

X-linked disorder causing deficiency in Hypoxanthine-Guanine Phosphoribosyl-transferase

  • > bases must be degraded to uric acid instead of being salvaged
  • > causes severe gout and self-mutilation tendencies like biting lips, indicating purine salvage pathways must be important to the brain
113
Q

What is the methodology by which purines are degraded?

A

Nucleotidases are used to remove 5’phosphates. Adenine is deaminated to return it to IMP (ketone). IMP / GMP have sugars removed by purine nucleoside phosphorylases, leaving just hypoxanthine / guanine. Guanine is deaminated to xanthine (leaves a ketone at C2), hypoxanthine is oxidized to xanthine (xanthine oxidase). Xanthine oxidase further oxidizes xanthine to uric acid

114
Q

What are the two enzymatic reactions carried out by xanthine oxidase, and why is this important?

A

Hypoxanthine -> xanthine
Xanthine -> uric acid

Blocked by allopurinol, a gout treatment

115
Q

What is primary vs secondary hyperuricemia? (gout)

A

Primary - innate defect in purine metabolism leading to more uric acid secretion

Secondary - increased purines available due to diet / medications

116
Q

What is a tophus?

A

Accumuluation of uric acid salts in cartilages / under skin (appears in joints)

117
Q

What is the underlying cause of severe-combined immunodeficiency (SCID)?

A

Adenosine deaminase deficiency -> accumulate dATP because adenine bases cannot be broken down

  • > inhibits ribonucleotide reductase (dATP is allosteric inhibitor)
  • > dATP buildup is toxic to lymphocytes!
118
Q

How is dihydroorotate produced via CAD?

A

C: CPSII, in the cytosol
Produces carbomoyl phosphate from HCO3- + NH2 group of Gln. Rest of atoms are from aspartate
A: Asparate transcarbamoylase
D: Dihydroorotase

Pumps out dihydroorotate

119
Q

Why is THF important in purine metabolism?

A

Need 2x 10-formyl-THF for 2 carbons in generic purine ring

120
Q

How is dihydroorotate converted to UMP?

A

Dihydroorotate -> orotate via dihydroorotate DH (linked to CoQ in ETC)
orotate -> OMP via orotate phosphoribosyltransferase
OMP -> UMP via orotidylate decarboxylase

Last two functions are carried out by UMPS

121
Q

What two enzymes are involved in UMP biosynthesis, then? What affects the activity of the first?

A

CAD and UMPS

CAD: inhibited by UTP but activated by ATP (keep the types of bases equal)

122
Q

How is CTP synthesized from UMP?

A

UMP double kinased to UTP.

UTP -> CTP via glutamine transfer of NH2 group, change ketone to amine (CTP synthetase, burns ATP)

123
Q

How does ribonucleotide reductase work?

A

Uses glutaredoxin / thioredoxin to remove 2’hydroxyl group via NADPH-dependent reduction mechanism.

Activity site is deactivated by dATP -> explains Lesch-Nyman lack of dNTPs
Specificity site: keeps nucleotides in balance and determines what nucleotides to deoxy-ify

124
Q

How is dTMP made? How does this explain B9 deficiency linked to b12?

A

from dUMP! Uses thymidylate synthase, requires 5,10-methyl-THF, which is made from serine (SHMT) or glycine (glycine cleavage system). Transfers methyl to dUMP, forming DHF as well.

If too much folate is trapped because of B12 deficiency (unable to use methionine synthase to regenerate THF), unable to make 5,10-methylene-THF used for thymidine synthesis.

125
Q

What is methotrexate’s target?

A

Blocks DHF to THF recycling via dihydrofolate reductase (competitive inhibitor). Prevents nucleotide synthesis

126
Q

What is Fluorouracil’s target?

A

Blocks thymidylate synthase -> anticancer, competitive inhibitor

127
Q

What are the two causes of orotic aciduria?

A
  1. UMPS deficiency -> buildup of orotate in purine biosynthesis pathway, not tied to hyperammonemia
  2. OTCase deficiency -> urea cycle defect, leads to excess orotic acid produced due to excess carbamoyl-P leaking into cytoplasm
128
Q

How can leptin be so high in obese individuals but not cause them to stop eating?

A

Leptin needs a transport system across BBB to reach hypothalamus. This transporter is inhibited by incredibly high levels of TAGs

129
Q

In what ways does PKA modify fatty acid metabolism?

A

Phosphorylates CPT1, making it less sensitive to inhibition via malonyl CoA -> FA oxidation

Phosphorylates acetyl-CoA carboxylase -> inhibits malonyl-CoA formation

130
Q

What receptors does epinephrine work on in adipose tissue, and what is the function?

A

Beta-adrenergic, GalphaS pathway phosphorylates HSL, cleaving TAGs.

131
Q

What receptors does epinephrine work on in liver?

A

Both alpha and beta, increase gluconeogenesis and glycogen breakdown.

132
Q

Where does HMG-CoA synthesis occur in cholesterol biosynthesis vs ketone body biosynthesis?

A

Cholesterol - cytoplasm

Ketone body - mitochondria

133
Q

What is beta-ketothiolase vs thiolase vs acetoacetyl-CoA transferase vs acetoacetyl-CoA thiolase?

A

All the same

Biochemistry (14 decks)

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