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DEMS > Unit III week 1 > Flashcards

Unit III week 1 Flashcards

1
Q

Categorization of 20 Amino Acids

5 methods to do this

A

1) Acidic or basic
2) Polar or nonpolar
3) Ability to synthesize or not
4) Specific chemical constituents
5) Use in energy synthesis

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2
Q

Essential vs. non-essential vs. conditionally essential AAs

A

Essential: cannot be synthesized by body, obtained from diet

Non-essential: can be synthesized from other amino acids

Conditionally essential: can be made by the body, but capacity for their synthesis is limited (especially in state of high consumption - e.g. illness)

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3
Q

Specific chemical constituents in AAs can be… (4)

A

Sulfur containing AAs

AAs with nitrogen in side chain (involved in N transport)

Branched amino acids

Aromatic amino acids (precursors for NTs and hormones)

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4
Q

How are proteins broken down in the gut?

A

GI tract → Peptidases: activated in gut lumen

Different specificities for specific types of peptide bonds

Sequentially break down long peptide chains into component AAs → absorbed and enter circulation

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5
Q

How are proteins broken down in tissues? (2 ways)

A

protein within cells also need to be broken down

1) Ubiquitination: targets proteins for degradation in proteasomes
2) Degradation in lysosomes

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6
Q

Amino acids contain a _______ group.

This means it must first be removed before use as a precursor for ___________.

This means it must be added before _______ is made from a carbon skeleton.

A

NH2

gluconeogenesis

Amino acid

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7
Q

Transamination reactions:

1) L-Amino acid donates NH3 to ________ –> ________ + ___________

catalyzed by ___________

2) Ammonia released as NH3 with regeneration of _________ –> _________

A

(bidirectional depending on substrate / acceptor availability)

NO production of anything, just shuttling something

1) AA donates NH3 to a-ketoglutarate → L glutamate + a-keto acid
Catalyzed by aminotransferase

2) Ammonia released as NH3 with regeneration of a-ketoglutarate
→ Urea cycle

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8
Q

Urea cycle:

1) NH3 –> ___________

catalyzed by ____________

A

NH3 → carbamoyl phosphate

Catalyzed by carbamoyl phosphate synthase 1

*Key regulated step in protein catabolism

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9
Q

Urea cycle:

2) Carbamoyl phosphate + __________ –> _________

A

Carbamoyl phosphate + NH3 (from aspartate) → urea

Urea: marker of AA catabolism and oxidation

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10
Q

Glutamine

A

nitrogen containing AA, accepts nitrogen from other AAs in peripheral tissues and carries it to liver/kidney

→ donates N to glutamate

→ a-ketoglutarate + NH3

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11
Q

Glutamine donates N to _________

Glutamate –> _________ + ________

This reaction is catalyzed by __________

A

glutamate

Glutamate –> a-ketoglutarate + NH3

catalyzed by glutamate dehydrogenase

Second key regulated step

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12
Q

Two key regulated steps of urea cycle:

A

1) NH3 → carbamoyl phosphate
Catalyzed by carbamoyl phosphate synthase 1

2) Glutamate → a-ketoglutarate catalyzed by glutamate dehydrogenase

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13
Q

Sulfur containing amino acids (2)

A

cysteine (non-essential AA)

methionine (essential AA)

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14
Q

Cysteine

A

can form disulfide bridges (change protein conformation)

-SH group

unessential amino acid

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15
Q

Glutathione (GSH)

A

highly soluble tripeptide that contains cysteine

1) Redox buffer (SH buffer) that maintains proteins in reduced forms (EX - reduces Fe3+ → Fe2+)
2) ROS protection: reduces hydrogen peroxide (H2O2) → H2O
3) Cofactor for several enzymes
4) uses Cys to control redox potential via GSH ← → GSSG

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16
Q

A-adenosylmethionine (SAM)

A

Met used to produce SAM (produced during first step of methionine degradation)

  • energy source for some biochemical reactions and important methyl donor
  • Precursor for homocysteine (B1 and folate metabolism)
  • SAM → S-adenosylhomocysteine (SAH)
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17
Q

Tetrahydrofolate

A

important one carbon methyl transfer reactions

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18
Q

Ring structure on side chains of what AAs? (3)

These are precursors for what important molecules? (7)

A

tryptophan, phenylalanine, tyrosine

Precursors for serotonin, niacin, dopamine, NE, epinephrine, tetrahydrobiopterin, thyroid hormone

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19
Q

Collagen

formation occurs via posttranslational modification from what 2 enzymes?

These reactions are _______ dependent

A

most abundant protein in human body, forms triple stranded helix

1) Prolyl hydroxylase
2) Lysyl hydroxylase

Vitamin C dependent

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20
Q

Hydroxyproline (Hyp)

-use?

___________ converts _____ to Hyp

A

used in collagen for H-bonding → increase collagen strength

Prolyl hydroxylase converts Pro to Hyp

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21
Q

Hydroxylysine (Hyl)

-use?

___________ converts _____ to Hyl

A

used in collagen for interchain cross-links

Lysyl hydroxylase converts Lys to Hyl

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22
Q

Gamma-carboxyglutamate (Gla)

-use?

_________ converts ______ –> ______

This reaction is _______ dependent

A

used to target proteins to membranes via Ca chelation

Glutamyl carboxylase converts Glu → Gla (vitamin K dependent)

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23
Q

Scurvy

A

both prolyl hydroxylase and lysyl hydroxylase rely on Vit-C (ascorbate) as a coenzyme

No Vit C → scurvy (Reduced collagen strength)

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24
Q

Vitamin C

A

cofactor for prolyl hydroxylase and lysyl hydroxylase enzymes used in collagen synthesis and strengthening

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25
Q

Vitamin K

A

used as cofactor for glutamyl carboxylase

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26
Q

Vitamin B6

A

used to make pyridoxal phosphate (PLP) → used by aminotransferases to “hold” / transfer amino groups during transamination reactions

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27
Q

Ubiquitin-Proteasome System

A

ATP dependent cross-linking of protein to ubiquitin (done by E1, E2 and E3 types)

Ubiquitinated proteins sequestered to proteasome → cellular trash can with proteolytic activity

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28
Q

Protein degradation: Lysosomal path

A

ATP independent, engulfs extracellular proteins (or live pathogen) → broken down by acid hydrolysis and lysosomal proteins (cathepsin)

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29
Q

Proteases (6)

A

secreted as proenzymes and cleaved in order to be activated

1) Pepsin
2) Enteropeptidase
3) Trypsin
4) Chymotrypsin
5) Carboxypeptidase-A
6) Carboxypeptidase-B

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30
Q

Pepsin

A

stomach

pepsinogen cleaved by HCl → pepsin→ cleave proteins

Aspartic protease: hydrolyzes N-terminal side of aromatic residues (Phe, Trp, Tyr)

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31
Q

Enteropeptidase

A

(intestine): cleaves trypsin into active form

Trypsinogen cleaved by enteropeptidase → trypsin

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32
Q

Trypsin

A

produced in pancreas → small intestine

cleaved into active form by enteropeptidase

Serine protease - hydrolyze C-terminal side of basic AA (Arg, Lys)

Trypsin cleaves all other zymogens in SI (chymotrypsinogen → chymotrypsin, pro carboxypeptidases → carboxypeptidase)

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33
Q

Chymotrypsin

A

serine protease - hydrolyzes C-terminal side of aromatic and some hydrophobic residues (Phe, Trp, Tyr, Leu, Met)

cleaved into activated form by trypsin

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34
Q

Carboxypeptidase-A

A

metallocarboxypeptidase - hydrolyzes C- terminal of hydrophobic AAs (Ala, Ile, Leu, Val)

cleaved into activated form by trypsin

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35
Q

Carboxypeptidase-B

A

cleaved into activated form by trypsin

metallocarboxypeptidase - hydrolyzes C-terminal of basic residues AAs (Arg, Lys)

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36
Q

Liver problems –> build up of what two enzymes?

A

Liver problems → build up of aminotransferases (ALT and AST) in blood

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37
Q

Alanine aminotransferase (ALT)

catalyzes what reaction

A

alanine + a-ketoglutarate ← → pyruvate + glutamate

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38
Q

Aspartate aminotransferase (AST)

catalyzes what reaction

A

aspartate + a-ketoglutarate ← → oxaloacetate + glutamate

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39
Q

Glu dehydrogenase

catalyzes what reaction?

A

Glutamate → a-ketoglutarate + NH3+

NH3 –> enters urea cycle

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40
Q

Aminotransferases require coenzyme _________ derived from _______

A

require coenzyme pyridoxal phosphate (PLP)

PLP is a derivative of B6

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41
Q

pyridoxal phosphate (PLP)

A

PLP is a derivative of B6
PLP “holds” amino group during its transfer
Used by aminotransferases as a conenzyme

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42
Q

Urea Cycle general overview

A

get rid of ammonia by forming less toxic compounds (urea)
-We do NOT store ammonia, and it’s toxic

  • Ornithine recycled in urea cycle
  • Occurs in mitochondria for part and cytosol for part

Entry points for nitrogen: aspartate and free ammonia

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43
Q

Overall reaction of urea cycle

A

3ATP + HCO3- + NH4+ + aspartate → 2 ADP + AMP + 2Pi + PPi + fumarate + urea

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44
Q

Tyrosine

used to make…?

A

Tyrosine → T4 (prohormone) → T3 (hormone)

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45
Q

Thyroid stimulating hormone (TSH)

A

stimulates iodide uptake + release of T4, T3

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46
Q

Thyroid peroxidase

A

oxidizes iodide (I-) → I2

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47
Q

Thyroglobulin (Tg)

A

contains Tyr residues iodinated to form T4, T3

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48
Q

Thyroxin binding globulin (TBG)

A

transports T3, T4

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49
Q

Porphyrin

A

cyclic molecules made of 4x pyrroles produced in liver

Bind Fe2+ (iron)

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50
Q

Heme synthesis

1) ______ + _______ –> __________

catalyzed by what enzyme
where in the cell does this occur?

A

Gly + succinyl CoA → d-Aminolevulinic acid (ALA)

Catalyzed by d-Aminolevulinate synthase

mitochondria

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51
Q

Heme synthesis

2) 2 d-Aminolevulinic acid (ALA) –> _______________

catalyzed by what enzyme
occurs where in the cell?

A

2 ALA → Porphobilinogen

Catalyzed by d-Aminolevulinate dehydratase

occurs in cytosol

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52
Q

Heme synthesis

3) Porphobilinogen –> –> –> –> __________ –> heme

the final step is catalyzed by what enzyme?
where in the cell does this occur?

A

Porphobilinogen → → → → Protoporphyrin → Heme

(catalyzed by ferrochelatase)

occurs in mitochondria

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53
Q

Porphyrin (heme) degradation:

1) Heme –> _______ –> _______
2) Bilirubin is transported in blood with ____________
3) Bilirubin is conjugated with ___________ in the _________ –> ______________

A

1) Heme → Biliverdin (green) → bilirubin (red-orange)
2) Albumin
3) Bilirubin conjugated with glucuronic acid in liver → bilirubin diglucuronide (conjugated bilirubin)

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54
Q

Porphyrin (heme) degradation:

4) Bilirubin diglucuronide (conjugated bilirubin) –> ________ –> _________

this occurs where?

A

→ bilirubin diglucuronide → urobilinogen → stercobilin (brown)

Occurs in intestine

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55
Q

Lead effect on heme - inhibits what two enzymes?

A

inhibits d-Aminolevulinate dehydratase and ferrochelatase
→ “Lead Poisoning”

Get Zn-protoporphyrin formation → fluorescent haze around RBCs

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56
Q

Urea cycle:

1) _______ + _________ –> Citrulline

catalyzed by what enzyme?
where in the cell?

A

Ornithine + Carbamoyl Phosphate → Citrulline

Catalyzed by Ornithine Transcarbamylase

Found in MITOCHONDRIA

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57
Q

Carbamoyl Phosphate Synthetase I

catalyzes what reaction?
located where in the cell?
activated by what?
uses what else in this reaction?

A

CO2 + NH3 → Carbamoyl Phosphate

**uses 2 ATP

MITOCHONDRIA

Activated by N-acetylglutamate**

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58
Q

N-acetylglutamate

A

Key activator required for carbamoyl phosphate synthetase I kick starting the Urea Cycle

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59
Q

How is N-acetylglutamate made?

______ + _______ –> N-acetylglutamate

catalyzed by _________
reaction is activated by ________

A

Acetyl CoA + Glutamate –> N-acetylglutamate

N-Acetylglutamate synthase

activated by Arginine

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60
Q

ORNT1

A

ornithine IN - citrulline OUT (of mitochondria)

antiporter

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61
Q

Urea Cycle

2) Citrulline + _________ –> _____________

catalyzed by what enzyme?
where in the cell does this take place?
what else is used in this reaction?

A

Citrulline + Aspartate → Argininosuccinate

Catalyzed by Argininosuccinate synthase (ASS)

Occurs in cytosol

uses ATP

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62
Q

Urea Cycle:

3) Arginosuccinate –> ________ + __________

catalyzed by what enzyme?
where in the cell does this take place?
what else is used in this reaction?

A

Argininosuccinate → Arginine + Fumarate

Catalyzed by Argininosuccinate lyase

Occurs in cytosol

doesn’t use anything else!

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63
Q

Arginine –> ______ + _______

catalyzed by what enzyme?
where in the cell does this take place?
what else is used in this reaction?

A

Arginine → Ornithine + Urea

Catalyzed by Arginase

Occurs in cytosol

doesn’t use anything else!

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64
Q

In nerves arginine can be converted directly into ________ and ______ via what enzyme?

A

Arginine → citrulline + NO (NO synthase)

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65
Q

In muscle, arginine can be converted directly into ________ and ________ for what purpose?

A

Arginine → ornithine → creatine phosphate for muscle energy

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66
Q

Four control points for protein catabolism:

A

1) Directionality of transamination (by ALT and AST) regulated by relative concentrations of “substrates” and “products”

2) N-acetylglutamate required activator of carbamoyl phosphate synthetase
Kick starts Urea Cycle

3) Directionality of oxidative deamination by Glu dehydrogenase depends on relative concentrations of Glu, a-ketoglutarate, NH3
4) ATP and GTP are allosteric inhibitors of Glu dehydrogenase, while ADP and GDP are activators

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67
Q

Ammonia is transported in the blood using ______ or _______

A

urea

glutamine

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68
Q

Glutamine

A

“holds” two ammonia groups

formed by glutamine synthetase

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69
Q

glutamine synthetase

A

converts glutamate → glutamine for transport to liver → enters urea cycle there
NOT in muscle

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70
Q

Glu dehydrogenase

why is it important?
what reaction does it catalyze?
what activates this reaction, what inhibits it?

A

control point for protein metabolism**
-Controls direction of nitrogen removal vs. incorporation into AAs

Glutamate + H2O ←→ a-ketoglutarate + NH4+

Inhibited by ATP and GTP
Activated by ADP and GDP

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71
Q

Cori Cycle

A

Pyruvate –> Lactate in muscle –> transported in blood to liver

Lactate –> pyruvate –> glucose in liver

Glucose sent to muscle for oxidation into pyruvate

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72
Q

Cahill Cycle - Alanine-Glucose Cycle

A

Glucose –> pyruvate –> alanine (transamination) in MUSCLE

Alanine transported in blood to liver

Alanine –> pyruvate (transamination) –> glucose in LIVER

glucose transported in blood to muscle

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73
Q

Gluconeogenic amino acids

-3 examples

A

produces pyruvate or TCA intermediates

Oxaloacetate (from aspartate transamination)
Asparagine
Aspartate

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74
Q

Ketogenic amino acids

-2 examples

A

no net production of glucose

Lysine and leucine → Acetyl CoA (2 carbons)

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75
Q

Maple Syrup Disease (MSUD)

A

deficiency in branched-chain a-ketoacid dehydrogenase complex

→ build up of a-keto acids in urine (“sweet smelling”)

leucine buildup is toxic

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76
Q

How are branched chain amino acids (leucine, valine, isoleucine) broken down?

(2 steps)

which one is deficient in MSUD?

A

1) Deaminated by branched-chain aminotransferase → a-keto acids

2) Decarboxylated by branched-chain a-ketoacid dehydrogenase
* *deficient in MSUD

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77
Q

Homocystinuria

defect where?

A

defect in cystathionine-b-synthase (CBS) or deficiency in Vit-B6

→ cannot convert homocysteine → cystathionine

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78
Q

Homocystinuria

presentation (4)

what are abnormal lab values? (2 key ones)

treatment (3) ?

A

Presentation:

1) DVT, stroke, atherosclerosis
2) Marfan-like habitus
3) Mental retardation
4) Joint contractures

Elevated homocysteine, elevated methionine (no megaloblastic anemia)

*on new born screening

TX:

  • Vit-B6 to “force” CBS activity
  • restrict methionine
  • betaine treatment +/- folate and B12
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79
Q

Hyperhomocysteinemia

defect where?
causes what?

A

elevated levels of homocysteine due to low folate, B6, and B12 (vascular disease)

Cysteine is now essential and treat with folate, B6, and B12

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80
Q

Cystinuria

defect where?
treatment?

A

kidney stones due to defective transporter of cystine → crystallization in urea

TX: acetazolamide (make cystine more soluble)

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81
Q

Cys and Met Metabolism (4 steps for Met, 5 steps for Cys)

A

Met → SAM → SAH → homocysteine → Met

OR

Met → SAM → SAH → homocysteine → cystathionine → cysteine

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82
Q

Conversion of homocysteine –> Methionine requires _____ and _____ for CH3 transfer

A

Homocysteine → Met requires THF and VB12 for CH3 transfer

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83
Q

Tetrahydrofolate (THF)

A

synthesized in bacteria, Folate → THF

One-carbon donor for variety of biosynthetic reactions

(used in homocysteine –> Met reaction)

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84
Q

Trp Metabolism:

Trp –> ______ or _______

Trp hydrolyzed by ____________ which uses _______ has a cofator

A

Trp → pyruvate or acetyl-CoA

hydrolyzed by tryptophan hydroxylase

Uses Tetrahydrobiopterin (BH4) as cofactor

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85
Q

Tryptophan is important for the production of what 3 things?

A

Trp → serotonin, melatonin, niacin

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86
Q

Phe and Tyr metabolism:

Phe, Tyr →_____________ or _________

A

fumarate or acetoacetate

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87
Q

Phe (hydroxylated by _________) → ______

Uses ______ cofactor

A

Phe (hydroxylated by phenylalanine hydroxylase) → Tyr

Uses BH4 cofactor

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88
Q

Tyr (hydroxylated by ________) → _______

Uses ______ as cofactor

A

Tyr (hydroxylated by tyrosine hydroxylase) → DOPA

Uses BH4 as cofactor

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89
Q

DOPA –> _________ or ________

uses _____ as cofactor

A

DOPA → catecholamines (dopamine, NE, epinephrine) or melanin

Uses BH4 as cofactor

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90
Q

BH4

cofactor for…(3)

A

1) Phenylalanine hydroxylase
2) Tyrosine hydroxylase
3) Tryptophan hydroxylase

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91
Q

Phenylketonuria (PKU)

A

defect in phenylalanine hydroxylase (convertes Phe–> tyrosine)

→ buildup of alternative byproducts (phenyllactate, phenylacetate, phenylpyruvate)

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92
Q

Tyrosinemia

A

defects in multi-step tyrosine degradation

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93
Q

Purines vs. Pyrimidines

A

Purines: guanine, adenine - 2 ringed base

Pyrimidines: uracil, thymine (DNA), cytosine (RNA) - 1 ring base

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94
Q

Nucleoside vs. nucleotide

A

Base = single or double ringed, contains N, C, O, and H

Nucleoside = base + pentose sugar

Nucleotide = base + ribose sugar + phosphate

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95
Q

Purine nucleotide synthesis overview

A

start with sugar, add phosphate (PRPP) to activate sugar –> add base

–> ends at IMP –> AMP, GMP

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96
Q

Pyrimidine nucleotide synthesis overview

A

start by making base –> add activated sugar (PRPP) –> ends at UMP –> UTP or dTMP

Unlike purines, pyrimidine base ring NOT made on ribose sugar - made separately and then base ring is added to sugar

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97
Q

Purine nucleotide synthesis:

1) Ribose -5-Phosphate –> __________

catalyzed by _________
uses _____
activated by ______
Inhibited by _______

A

1) Ribose 5-phosphate → 5-Phosphoribosyl-1-pyrophosphate (PRPP, ACTIVATED SUGAR)

Catalyzed by PRPP Synthetase
Uses ATP
Activated by Pi
Inhibited by purine ribonucleotides

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98
Q

Purine nucleotide synthesis:

2) PRPP + _______ –> adds first N to PRPP

catalyzed by \_\_\_\_\_\_\_\_\_\_\_
inhibited by (3)
activated by (1)
A

RPP (contains ribose sugar) + Glutamine → add first N to PRPP

Via glutamine Phosphoribosylpyrophosphate amidotransferase

KEY STEP

Inhibited by AMP, GMP, IMP
Activated by PRPP

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99
Q

What is required for purine synthesis (4)

A

glycine
glutamine
THF
aspartate

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100
Q

What is required for pyrimidine synthesis (1)

A

aspartate

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101
Q

Purine synthesis:

after N is added to PRPP –> –> a few steps later you make _________ which can then generate ______ and _______

A

Inosine Monophosphate (IMP)

→ GMP + AMP

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102
Q

AMP –> ATP how?

GMP –> GTP how?

A

AMP* + ATP ← → 2 ADP* (via adenylate kinase)
ADP + CTP ← → ATP* + CDP

GMP* + ATP ← → GDP* + ADP (via guanylate kinase)
GDP + ATP ← → GTP* + ADP

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103
Q

Pyrimidine synthesis:

1) ______ + CO2 –> ________

catalyzed by ___________ where in the cell?
inhibited by _____
activated by _______

A

Glutamine + CO2 –> carbamoyl phosphate

Via Carbamoyl Phosphate Synthetase II: in cytosol

Activated by PRPP
Inhibited by UTP

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104
Q

Pyrimidine synthesis:

2) Carbamoyl phosphate + _________ –> –> –> eventually generates _________

A

Aspartate

Generates Uracil Monophosphate (UMP)

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105
Q

Pyrimidine synthesis:

3) Once UMP is made, it can generate…(2 pathways)

A

1) UMP → UDP –> UTP → CTP (Via CTP synthase)

2) UMP –> UDP –> dUTP (via ribonucleotide reductase) –> dUMP –> dTMP

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106
Q

Purine breakdown overview

A

base removed from sugar → free base (adenosine/guanine)

Bases broken down to uric acid → excreted in urine

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107
Q

Purine breakdown:

1) AMP –> ______

2) Adenosine –> ________
- what enzyme?

3) -> hypoxanthine –> __________
- what enzyme?

4) Xanthine –> ________
- what enzyme

A

AMP → Adenosine

Adenosine→ Inosine (Adenosine deaminase)

→ hypoxanthine → xanthine (xanthine oxidase)

Xanthine → uric acid (xanthine oxidase)

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108
Q

Pyrimidine breakdown

A

base ring removed from ribose (same as purines)

→ base ring OPENED UP → Succinyl-CoA, Malonyl-CoA, Acetyl-CoA

NO toxic intermediates

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109
Q

Salvage Pathways

-two main enzymes used?

A

nucleotides made from partially degraded, reused nucleotides
-Free bases attached to ribose sugar (PRPP)

1) Guanine + PRPP → GMP (by HGPRT)
2) Hypoxanthine + PRPP → IMP (HGPRT)
3) Adenine + PRPP → AMP (by adenine phosphoribosyl transferase (APRT))

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110
Q

Ribonucleotide Reductase

A

converts ribose to deoxyribose

Operates on diphosphates (NDPs, ADP, GDP, CDP, UDP)

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111
Q

Regulation of ribonucleotide reductase

A

Primary regulation site (“on/off” switch) for overall enzyme activity → active in presence of ATP, inactive with high dATP

Substrate specificity site (“dial”): sensitive to concentrations of individual dNTPs → enzyme changes specificity based on what NDP is in highest concentration
→ equal amounts of each NDP → dNDP

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112
Q

Gout

A

buildup of uric acid in blood due to deficiency or hyperactivity of enzymes in purine degradation pathway

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113
Q

Severe Combined Immunodeficiency Syndrome (SCID)

A

mutation in adenosine deaminase gene

→ build up of dATP → inhibits ribonucleotide reductase → prevents enough dNTPs from being made

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114
Q

Lesch-Nyhan Syndrome

deficiency in what?
presentation? (3)

A

deficiency in purine salvage pathway (HGPRT) → higher rates of de novo purine synthesis

Presentation: gout symptoms, self-mutilating behavior, severe mental disorders

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115
Q

5-Fluorouracil targets _______ and Methotrexate targets __________

A

targets thymidylate synthase (5-FU)

targets folate metabolism cycle (Methotrexate

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116
Q

6-mercaptopurine inhibits ________

A

inhibits de novo purine synthesis (inhibits AMP synthesis)

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117
Q

Azidothymidine (AZT) inhibits ___________

A

viral polymerase

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118
Q

Cytosine arabinoside (araC) targets __________

A

targets DNA polymerase (anti leukemia)

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119
Q

Acyclovir (ACV) targets _______ and _________

A

targets viral DNA polymerase and reverse transcriptase (anti HSV)

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120
Q

Hydroxyurea inhibits __________

A

ribonucleotide reductase

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121
Q

Acute intermittent porphyria is a deficiency in ___________ enzyme.

Inheritance?

A

Problem with porphobilinogen deaminase (converts porphobilinogen → hydroxymethylbilane)

AD, episodic, variable expression

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122
Q

Acute intermittent porphyria

Presentation (5)

A

1) Late onset
2) Anxiety, confusion, paranoia
3) Acute abdominal pain
4) NO photosensitivity
5) Port-wine urine

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123
Q

What should you NEVER give a patient with Acute intermittent porphyria? Why?

A

NEVER give barbiturates (induce CYP450 → increase heme consumption → decrease [heme] → no ALA synthetase inhibition → build up of heme synthesis intermediates)

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124
Q

Porphyria Cutanea Tarda is a deficiency in _________ enzyme

inheritance?

A

Problem with uroporphyrinogen decarboxylase (converts uroporphyrinogen → coproporphyrinogen)

Most common Porphyria

AD

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125
Q

Porphyria Cutanea Tarda

Presentation (5)

A

1) Late onset
2) Photosensitivity - inflammation, blistering, shearing of skin with sun exposure
3) Hyperpigmentation
4) Exacerbated by alcohol
5) Red/brown urine

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126
Q

Albinism is a defect in ________ enzyme, a part of ________ metabolism that produces melanin

A

defect in tyrosinase (converts tyrosine → melanin)

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127
Q

Alcaptonuria is a defect in _________ enzyme, part of the _______ and ______ breakdown pathway

A

defect in homogentisate oxidase (phenylalanine and tyrosine breakdown pathway)

128
Q

Alcaptonuria

presentation (3)

A

dark urine (blue/black)**, ochronosis, arthritis

129
Q

How do you differentiate hyperhomocysteinemia due to low folate vs. low B12

A

Low folate → megaloblastic anemia, elevated homocysteine, decreased methionine, normal methylmalonic acid

Low B12 → megaloblastic anemia, elevated homocysteine, decreased methionine, ELEVATED methylmalonic acid (B12 also a cofactor for methylmalonyl CoA mutase)

130
Q

Methionine degradation and cysteine synthesis

1) Met → _______ via transfer of methyl group
2) SAM → ________
3) SAH → _________
4) Homocysteine broken down into _________ via ________ enzyme and cofactors or _________ requiring _______ enzyme and cofactors
5) finally, cystathionine –> _________

A

1) Met → SAM (S-adenosylmethionine) via transfer of methyl group
2) SAM → S-adenosylhomocysteine (SAH)
3) SAH → Homocysteine

4) Homocysteine
→Methionine via Homocysteine Methyltransferase (B12 and THF cofactor) **

OR
→ Cystathionine via Cystathionine Synthase (B6 cofactor**)

5) Cystathionine → Cysteine

131
Q

Treatment of PKU

A

dietary restriction of phenylalanine

  • avoid aspartame
  • Sapropterin (BH4 cofactor supplement) for patients with some residual enzyme activity

-Must also treat mothers with PKU to prevent problems in infant

132
Q

Manifestations of untreated PKU

A

intellectual disability, hypopigmentation, eczema, hypomyelination on brain MRI

133
Q

How is PKU usually diagnosed

A

Newborn screening for PKU: diagnosed nearly 100% of time

  • Presence of hyperphenylalaninemia using Guthrie microbial assay on blood spot
  • NBS via tandem mass spectrometry (test for PKU + many other diseases)
134
Q

Presentation of Maple Syrup Urine Disease (MSUD)

A

1) Maple syrup odor in cerumen 12-24 hrs after birth
2) Ketonuria
3) Irritability, poor feeding by age 2-3 days
4) Encephalopathy - lethargy, intermittent apnea, opisthotonus
5) Cerebral edema
6) Stereotyped movements (“fencing”, “bicycling”) by 4-5 days
7) Coma and central respiratory failure by 7-10 days

**Reversible with treatment

135
Q

Diagnosis of MSUD (6)

A

presence of clinical features

\+decreased levels of BCKAD enzyme
\+presence of all-isoleucine
\+elevated leucine
\+urine ketones
\+gene sequencing

**Newborn screening done for MSUD

136
Q

Treatment of MSUD

A
  • dietary leucine restriction
  • high calorie BCAA-free formulas
  • judicial supplementation with isoleucine and valine (only leucine is toxic)
  • frequent monitoring
  • Liver transplant
137
Q

Tyrosinemia Type I is due to a deficiency in ____________ enzyme

A

Deficiency of enzyme fumarylacetoacetate hydrolase (FAH)

138
Q

Tyrosinemia Type I

Presentation

A

1) Acute liver failure in infancy, later as hepatocellular carcinoma
2) Hyperbilirubinemia, jaundice, ascites, coagulopathy, hepatomegaly
3) Rickets
4) Neurologic crises, abdominal pain
5) Death occurs in untreated child before age 10 from liver failure, neurologic crisis, or hepatocellular carcinoma

139
Q

Urea cycle disorders

A

Defects in metabolism of waste nitrogen from the breakdown of protein and other nitrogen-containing molecules

Deficiency in the six enzymes of the urea cycle pathways: CPS1, OTC, ASS1, ASL, ARG, NAGS

140
Q

Presentation of urea cycle disorders

severe vs. partial

A

Severe UCD → accumulation of AMMONIA during first few days of life → normal at birth with rapid progression to cerebral edema, lethargy, anorexia, hyper/hypoventilation, hypothermia, seizures, neurologic posturing, coma

Partial UCD → ammonia accumulation triggered by illness or stress

141
Q

Screening for urea cycle disorders

A

plasma ammonia concentration > 150 umol/L or higher with normal anion gap and normal plasma glucose

Definitive diagnosis with enzyme activity assay or genetic testing

Certain deficiencies may be present on newborn screening (ASS1, ASL, ARG deficiencies)

*OTC is not

142
Q

Ornithine transcarbamylase deficiency (OTC)

A

most common urea cycle defect (X-linked)
OTC ONLY expressed in liver
Lethal in neonatal period for boys
**OTC is NOT on newborn screening

143
Q

Diagnosis of OTC deficiency and treatment

A

Diagnosis: diagnostic metabolite is orotic acid with low citrulline, high glutamine

Treatment: VERY LOW protein diet, supplement citrulline/arginine, close nutritional monitoring

  • Dialysis
  • Liver transplant is curative
144
Q

Lysosomal Storage Diseases (LSD)

-examples (7)

A

occur when a lysosomal enzyme is deficient/missing resulting in substrate accumulation (storage) in various organs and dysfunction

PROGRESSIVE diseases that present less acutely than other metabolic conditions

1) Fabry
2) Gaucher
3) Hunter
4) Hurler
5) Pompe
6) Tay Sachs
7) McArdle

145
Q

Key signs of storage/accumulation in lysosomal storage diseases

A

Macrocephaly, cognitive regression

Coarseness, angiokeratoma

Corneal clouding, cherry red spot (Tay Sachs)

Macroglossia, sleep apnea

Hepatosplenomegaly

Proteinuria

Dysostosis multiplex (vertebral “beaking”, broad bases of metacarpals and phalanges, scoliosis)

Joint stiffness, short stature

146
Q

Inheritance of lysosomal storage diseases

A

most AR, with a few exceptions

Fabry (alpha-galactosidase) = X-linked Dominant

Hunter syndrome (iduronate-2-sulfatase) = X-linked Recessive

147
Q

Lysosomes

A

single membrane bound, intracellular organelles

Acidic, hydrolase-rich, capable of degrading macromolecules into smaller components

Hydrolases only active in acidic environment of lysosome

148
Q

Fabry disease

inheritance?

-differences in presentation based on age (teen, adult, older adult)?

A

X-linked dominant (mostly men)

  • Preteen/teen onset with neuro findings
  • Adult with renal failure
  • Older adult with LVH or stroke
149
Q

Fabry Disease

5 key features

A

1) ACROPARESTHESIAS** (pain in palms/soles + fever)
2) Proteinuria and RENAL FAILURE**
3) LVH/stroke
4) Dark red, ANGIOKERATOMAS** (bathing suit distribution)
5) Family history of early renal failure in male relatives

150
Q

What enzyme is deficient in fabry disease?

A

Alpha-galactosidase

151
Q

Is there a treatment for fabry disease?

A

agalsidase beta

152
Q

Gaucher Disease Type 1

inheritance?
onset at what age?

A

AR, adult onset

153
Q

Gaucher Disease Type 1

Key features (5)

A

1) Hepatosplenomegaly (enlarging abdomen)
2) Anemia (fatigue)
3) Thrombocytopenia
4) Looks like “lymphoma” (BIG SPLEEN/anemia) but isn’t
5) BONY PAIN

154
Q

Enzyme deficient in Gaucher Disease Type 1

A

Beta-glucosidase (aka glucocerebrosidase)

155
Q

Is there a treatment for Gaucher Disease Type 1?

A

enzyme replacement, oral substrate inhibition

156
Q

Hunter and hurler disease

inheritance?
onset at what age?

A

Hunter = XR, onset in childhood

Hurler = AR, onset in childhood

157
Q

Key features shared by hunter and hurler synromes (6)

A

1) Coarse facies
2) Airway disease
3) Ear infections
4) Hoarse voice
5) Hepatosplenomegaly
6) Short stature

158
Q

2 main features that differentiate hunter and hurler syndromes

A

1) MALE (Hunter), FEMALE (Hurler)**

2) NO CORNEAL CLOUDING (Hunter) CORNEAL CLOUDING (Hurler)

159
Q

Enzyme involved in Hunter syndrome

A

iduronate sulfatase

treat with recombinant enzyme - Idursulfase

160
Q

Enzyme involved in Hurler syndrome

A

Alpha iduronidase

treat with recombinant enzyme - Iaronidase

161
Q

Pompe Disease

inheritance?
key organs involved?

A

AR

Organs involved: skeletal muscles, heart (infant only)

162
Q

Pompe Disease

Clinical presentation

A
  • Infant with progressive MUSCLE WEAKNESS and SEVERE LVH
  • Normal intelligence
  • Infant presents at 3-6 months, dead at 1 yr w/o treatment

Adult with proximal MUSCLE WEAKNESS and RESPIRATORY WEAKNESS (sleep apnea)
-Normal intelligence

163
Q

Key features of pompe disease

infant vs. adult

A

1) Infant with muscle weakness, high CK, and LVH on ECG

2) Adult with sleep apnea and trouble climbing stairs

164
Q

Enzyme deficient in pompe disease

A

alpha-glucosidase

treat with recombinant enzyme - alglucosidase alfa

165
Q

Tay Sachs Type I

inheritance
age of onset?

A

AR, infantile/early adulthood onset

166
Q

Ket features of Tay Sachs (6)

A

1) Increased startle reflex
2) Blindness**
3) Seizures
4) CHERRY RED SPOTS**
5) Mental/motor deterioration
6) Likely will die

167
Q

Enzyme deficient in Tay Sachs

A

Beta-hexosaminidase A

168
Q

Is there a treatment for Tay Sachs?

A

No - supportive only

169
Q

McArdle disease

inheritance?
age of onset?

A

AR, adult onset

170
Q

Key features of McArdle (3)

A

1) Muscle weakness and cramping with exercise
2) “Second Wind” phenomenon (weak upon initial exercise, then gets “second wind”
3) High CK

171
Q

Enzyme deficient in McArdle

Is there a treatment for McArdle?

A

glycogen phosphorylase

TX = supportive

172
Q

Feeding a hospitalized patient depends on what 4 factors?

A

1) Patient’s preexisting nutritional status
2) Patient’s level of illness
3) Consequences to patient of inadequate nutrition
4) Risks of feeding them

173
Q

Enteral administration

A

tube inserted into GI tract via mouth, nose, or through abdominal wall

Risks: aspiration of food into lungs

Administration:
Start infusion at lower infusion rate, and gradually increase flow rate of diet over a period of days

Check residuals (amount of food still in stomach)

If you cannot give enteral diet at a rate sufficient to meet TEE then give some enteral nutrition with parenteral nutrition

Enteral preferred over parenteral

174
Q

Parenteral administration

A

IV feeding

Risks: infection from a central line that contains nutrients in high concentration

Should administer enteral when possible

175
Q

What to feed - Estimating calories/day needed

A

Someone not that sick → 22-25 kcal/kg/day, very sick → 30-32 kcal/kg/day

Multiple by kg, then 1 kcal/ml, then divide by hours → hourly infusion rate

176
Q

How to monitor the adequacy of feeding?

What are signs of overfeeding?

A

once glycogen stores are filled → pt develops hyperglycemia

→ reduce number of calories they get each day, may take days for situation to reverse itself

177
Q

How to monitor the adequacy of feeding?

What are signs of underfeeding?

A

Underfeeding → break down muscle to donate AAs to gluconeogenesis → lose weight over time, can measure urinary nitrogen over 24 hrs

Number of grams of protein catabolized = grams urinary nitrogen x 6.25

grams of protein catabolized > protein you are feeding them → underfeeding them

178
Q

Special issues associated with feeding hospitalized patients:

Respiratory failure patient

A

Overfeeding → increases rate of oxidation of nutrients → consume more O2 and produce more CO2

DO NOT OVERFEED

Consider feeding people on a ventilator a high fat, low calorie diet

More CO2 produced for each O2 consumed when glucose is burned compared to fat

179
Q

Special issues associated with feeding hospitalized patients:

Liver failure patient

A

High levels of ammonia + high aromatic AA + ascites → limit protein, salt, water intake

180
Q

Special issues associated with feeding hospitalized patients:

Renal failure patient

A

Kidneys responsible for excreting urea → limit protein catabolism, limit volume and salt

181
Q

Special issues associated with feeding hospitalized patients:

Cardiac disease patient

A

Low fat, low sodium, low saturated fat diet = “Cardiac diet”

Restrict Na+ due to volume overload (CHF)

Restrict energy in overweight or obese patients

182
Q

Special issues associated with feeding hospitalized patients:

Diabetic patient

A

“Diabetic diet” = restricted calories, fat, and simple sugars

Control carb content with each meal so insulin dose can be tailored to carbs

May want to feed patient more like how they would eat at home so medications/insulin can be adjusted to a more realistic diet

183
Q

Risk for Nutritional Problems (7)

A 
Very young
Very old
Underweight/overweight
Hypermetabolic
Alcoholic
Impoverished/marginalized/altered mental capacity
Chronic conditions
184
Q

Chronic conditions that put patients at risk for nutritional problems

A

Decreased absorption: CF, celiac disease

Increased losses: blood loss, diarrhea

Increased requirements: growth, pregnancy, lactation, pulmonary/cardiac disease

185
Q

Obtaining Diet Intake Information (4)

A

History - risk, diet

Anthropometry - BMI, waist circumference

Physical Exam - skin (rash, petechiae, bruising, pallor), hair (color, texture), mouth (sores, cracked lips, tongue), extremities
-Loss/gain of subcutaneous fat, muscle wasting, edema, neuro exam, mouth

Labs - albumin, prealbumin, transferrin, CBC, specific nutrient level

186
Q

Estimated Average Requirement (EAR)

A

estimated adequate intake for 50% of population - used to assess inadequate intakes and planning goal intake for mean intake of POPULATIONS

EX) need X amount if Vit C to prevent scurvy

187
Q

Recommended Dietary Allowance (RDA)

A

meets requirements for 95-87% of population (i.e. it’s set high) - used as goal for HEALTHY individuals (NOT to assess/plan diets of groups)

Applies to INDIVIDUALS not groups

188
Q

Actual estimates of intakes of food and/or nutrients: (2)

A

1) 24 hour recall/typical day: quick, easy, good for diets with limited variability, may not be representative of usual intake better assessment of food patterns
2) Diet record (including multiple days): better estimate of average food/nutrient intakes, time consuming, may change eating behavior

189
Q

To achieve change you must…(2)

A

1) Reduce difficulty

2) Increase motivation

190
Q

Readiness to change

A

importance (is change worthwhile) and confidence (where pt believes he/she can change)

191
Q

How to address dietary and lifestyle changes with a patient:

A

Traditional dietary counseling focuses on WHAT patient should eat, concept of WHY they eat as they do and impediments to changing dietary behavior less understood and less emphasized

Failure to change diet in most patients is NOT result of inadequate motivation, but of excessive difficulty/barriers

-focus on readiness to change, increasing motivation, and decreasing barriers

192
Q

Aim of US Dietary Guidelines

A

Target healthy public over age of 2

Promote health and aim to reduce risk of chronic disease, including obesity, cardiovascular disease, diabetes, and some cancers (Ironically doing the opposite of what it is intended to do)

Science-based (more like big money based) advice to promote health and reduce risk for major chronic diseases through diet and physical activity for general public

Yes I am very fucking bitter

193
Q

2015-2020 Dietary Guidelines

5 key messages

A

1) Healthy eating pattern across a lifetime
2) Focus on variety, nutrient density, amounts
3) Limited calories from added sugars, saturated fats and reduce sodium intake
4) Healthier food and beverage choices (fiber/whole grain, low/non-fat dairy, chips→ nuts, soft drinks → water)
5) Be active

194
Q

Guidelines for sugar, saturated fatty acids, and sodium intake

A

Added sugar < 10% of total daily calories

< 10% calories from saturated fatty acids, and limit trans fats to as low as possible

Reduce sodium intake to < 2300 mg/d

195
Q

How typical dietary patterns and food choices differ in US from DG

A

Dietary practices “divergent” from recommendations considered to be 2nd leading cause of preventable death in US
-Unhealthy eating and inactivity contribute to 310,000-580,000 deaths/yr

Consume too few green vegetables, orange vegetables, legumes, and whole grains, fruits, low fat dairy, and seafood
-Only 6% and 8% achieve their recommended target intakes for vegetables and fruits respectively in average day

Excess intake of solid fats and added sugars, refined grains, and sodium

Caloric intake exceeds energy expended

196
Q

3 benefits of a diet rich in vegetables, fruits, whole grains, low fat dairy, healthy oils:

A

Reduced mortality, cardiovascular disease, and blood pressure

197
Q

Water soluble vitamins

A

not stored (Except B12), highly absorbed from diet, excreted via urine, low toxicity

Chronic intakes DO alter tissue levels

198
Q

Types of water soluble vitamins (4 categories)

A

Non B-Complex: Ascorbic acid (Vit C)

B-Complex:
-Energy metabolism: thiamin, niacin, riboflavin, pantothenic acid

  • Hematopoietic: folic acid, B12
  • Other: B6, Choline, Inositol, Biotin
199
Q

Fat soluble vitamins

A

accumulate “stores” in body, potential for toxicity with excess intake

Require absorption of dietary fat and carrier system for transport in blood

Includes Vit A, D, E, K

200
Q 
Vitamin A:
Biochemical function (4)
A

1) Essential photochemical basis of vision
2) Maintains conjunctival membranes and cornea
3) Critical for epithelial cellular differentiation and proliferation
4) Immune regulation (serum levels DECREASED with inflammation = NEGATIVE acute phase reactant)

201
Q

Vitamin A

Major dietary sources

A

Pre-formed VitA: liver, dairy, egg yolks, fish oil (animal sources)

Precursor (Beta-Carotene): deep yellow/orange and green vegetables (spinach, carrots, broccoli, pumpkin)

202
Q

Vitamin A

Characteristic deficiency findings

A

1) Night blindness
2) Xerophthalmia (extreme dryness of cornea) → Bitot’s Spots
3) Epithelial linings become flat, dry, and keratinized
4) Immune impairment (ex - treat measles with Vit A)

203
Q

Vitamin A

Characteristic toxicity findings

how does toxicity occur?

A

can ONLY occur with PREFORMED Vit A intake

-can occur with Accutane

Vomiting, increased ICP, headache, bone pain, bone mineral loss, liver damage, death, birth defects

204
Q

Vitamin A

Lab findings

A

serum retinol (will be normal until liver stored depleted)

serum levels DECREASED with inflammation = NEGATIVE acute phase reactant

205
Q

Vitamin A

Risk for deficiency

A

poor or extreme low fat diet

206
Q

Vitamin D

Biochemical function

A

acts as a hormone (plasma membrane and nuclear receptors in a range of tissues)

1) Maintain intra/extracellular Ca2+
- Stimulate intestinal absorption Ca2+ and P
- Stimulate renal reabsorption of Ca2+ and P
- Mobilize Ca2+ and P from bone

2) Innate immune function (generation of toxic radicals)
3) Cellular growth and differentiation through nuclear and plasma membrane vitamin D receptors

207
Q

Vitamin D

Major dietary sources

A

Precursor in skin: UVB light → converted to cholecalciferol (D3)

Diet: fish liver oils, fatty fish, egg yolks, fortified milk and formulas

D3 activity 2-3x > D2

208
Q

Vitamin D

Metabolism - 3 steps

A

1) Absorbed by chylomicrons (requires fat absorption)
2) D2 or D3 hydroxylated in liver → 25-hydroxy-cholecalciferol
3) Kidney → 1,25-dihydroxy-cholecalciferol (calcitriol) = ACTIVE FORM

209
Q

Vitamin D

Characteristic deficiency findings (2)

A

Rickets (25OH-D < 11 ng/mL) = failure of maturation of cartilage and calcification → bowed legs, widened metaphyses, painful bone fractures

Adult osteoporosis

210
Q

Vitamin D

Characteristic toxicity findings

risk of toxicity increased with what types of diseases?

A

Hypercalcemia, vomiting, seizures, nephrocalcinosis, soft tissue calcification

Risk of Vit-D toxicity with chronic granulomatous diseases (e.g. sarcoidosis)

211
Q

Vitamin D

Lab findings

A

serum 25(OH) Vit D levels

TEST 25-OH Vit D → level reflects BODY STORES

212
Q

Vitamin E

Biochemical function (3)

A

antioxidant, free radical scavenger, cell membrane stabilizer

213
Q

Vitamin E

Major dietary sources

A

polyunsaturated vegetable oils, wheat germ

214
Q

Vitamin E

Characteristic deficiency findings (2)

A

Neurologic degeneration (loss of DTRs, neuropathy, ophthalmoplegia, spinocerebellar ataxia) = IRREVERSIBLE

Hemolytic anemia

215
Q

Vitamin E

Characteristic toxicity findings (1)

A

1) coagulopathy - inhibit Vitamin K dependent clotting factors

(low risk of toxicity)

216
Q

Vitamin E

Risk for deficiency (1)

A

prematurity

217
Q

Vitamin K

Biochemical function

A

essential for carboxylation of coagulation factors (2, 7, 9, 10, protein C and protein S)

218
Q

Vitamin K

Dietary sources

A

leafy vegetables, fruit, seeds, synthesis by intestinal bacteria

219
Q

Vitamin K

Characteristic deficiency findings (2)

A

1) Prolonged coagulation times (increased PT, increased PTT, normal bleeding time)
2) Hemorrhagic disease of newborn (give Vit-K injection)

220
Q

Vitamin K

Risks for deficiency (3)

A

Newborn, antibiotics, poor diet

221
Q

High risk of vitamin D deficiency with…(6)

A

1) Low sun exposure (Winter, dark skin pigmentation)
2) Low dietary intake
3) Fat malabsorption
4) Breastfed infants
5) Obesity (fat sequestration, sedentary)
6) Liver or renal disease → must use calcitriol (active form), because cannot activate VitD

222
Q

Numbers indicating dietary deficiency of Vitamin D

deficient, insufficient, sufficient

A

Deficiency = 25-OH < 20 ng/mL
Insufficiency - 21-29 ng/mL
Sufficient >/= 30 ng/mL

223
Q

Energy Releasing Vitamins include… (3)

A

Thiamine (B1), Riboflavin (B2), Niacin (B3)

  • All involved in glycolysis / TCA
  • TPP, FAD, NAD
  • decarboxylation, oxidation-reduction
224
Q

Thiamine (B1)

Function

A

Thiamine pyrophosphate (TPP or TDP): coenzyme central to metabolism (glycolysis, TCA cycle, AA metabolism, decarboxylation, transketolation reactions)

225
Q

Thiamine (B1)

Dietary sources (3)

A

rich in whole grains, lean porks, legumes

226
Q

Thiamine (B1)

Deficiency findings:

A

Beriberi: nervous and cardiovascular effects

227
Q

Thiamine (B1)

3 kinds of BeriBeri

A

Dry Beriberi = peripheral neuropathy, muscle tenderness (esp legs), weakness, atrophy (foot drop)

Wet Beriberi = cardiac → edema, circulatory collapse, CHD

Wernicke-Korsakoff Syndrome = “cerebral Beriberi” TRIAD→ ocular signs (nystagmus, ophthalmoplegia), ataxia, amnesia / confusion

228
Q

Thiamine (B1)

Populations at risk of deficiency

A 
alcoholics*
vomiting
elderly
chronic renal dialysis
refeeding after starvation
bariatric surgery
229
Q

Riboflavin (B2)

function

A

Coenzyme = FAD, FMN → oxidation/reduction in TCA cycle and oxidative phosphorylation

AA and fatty acid metabolism

Metabolism of Vit K, Folate, B6, and Niacin

230
Q

Riboflavin (B2)

Dietary sources (3)

A

dairy, eggs, meats

231
Q

Riboflavin (B2)

Deficiency findings (3 areas)

A

oral-ocular-genital syndrome

Oral → cheilosis (cracked lips) angular stomatitis (sores in mouth corner)

Ocular → increased vascularization of conjunctiva, photophobia

Genital → seborrheic dermatitis and scrotal dermatitis

232
Q

Niacin (B3)

Function

A

Nicotinamide in NAD and NADP - key for energy related pathways

233
Q

Niacin (B3)

Dietary sources

what is a precursor for B3?

A

Preformed → meat, poultry, fish, peanut butter, legumes

TRYPTOPHAN = precursor → milk, eggs (rich in tryptophan)

234
Q

Niacin (B3)

Deficiency findings

A

PELLAGRA 4 D’s

Dermatitis: symmetric pattern, aggravated by sun, heat exposure

Dementia: confusion, dizziness, hallucinations

Diarrhea

Death

235
Q

Niacin (B3)

Risks for deficiency

A

Nutritional/dietary restriction
Malabsorption syndromes
Alcoholism
Metabolic “shunting” (carcinoid tumor → increased serotonin → decreased tryptophan)

236
Q

Folate

Function

A

1-carbon transfers (especially in synthesis of nucleic acids and metabolism of AAs) and DNA methylation

Conversion of homocysteine → methionine

Methyl donor

Epigenetics

237
Q

Folate

Dietary sources

A

foliage (deep green leaves, broccoli, orange juice, whole grains)

238
Q

Folate

Deficiency findings (6)

A

1) *Macrocytic anemia
2) *hypersegmented neutrophils
3) *Glossitis
4) *Increased plasma homocysteine (homocysteinemia)
5) *Decreased plasma methionine
6) *Neural tube defects

239
Q

Folate deficiency lab findings

A
  • serum folate (shows recent intake)
  • RBC folate (shows tissue stores / chronic status)
  • increased homocysteine
  • decreased methionine
  • Macrocytic anemia
240
Q

Risks for folate deficiency (5)

A

Inadequate intake or increased destruction in cooked foods

Alcoholics

Pregnancy - **Women of childbearing age advised to have intake of 400 ug/d to prevent neural tube defects (must begin supplementation before they know they are pregnant)

Hematopoietic conditions

Drug/nutrient interactions

241
Q

Vitamin B12 (Cobalamin)

Function + name two key enzymes it is a cofactor for

A

1 carbon transfers, nucleic acid synthesis, protein synthesis

Metabolism of odd chain fatty acids (methylmalonyl CoA mutase)

Re-forms THF from methylfolate (homocysteine methyltransferase)

242
Q

Vitamin B12 (Cobalamin)

Dietary sources

A

animal products only

243
Q

Vitamin B12 (Cobalamin)

absorption and storage

A
  • Takes years to develop deficiency (liver stores 1-10 mg)
  • Excreted and recycled in bile

Absorption:

  • Cleave vitamin from dietary protein in stomach
  • Requires Intrinsic Factor from stomach
  • Cobalamin-IF absorbed in distal ileum
  • Transport in circulation by transcobalamin II
244
Q

Vitamin B12 (Cobalamin)

Deficiency findings (5)

A

Macrocytic anemia with hypersegmented neutrophils

Neurologic disturbances (eventually IRREVERSIBLE)
*DO NOT treat macrocytic anemia with folate unless B12 deficiency ruled out (will correct anemia but NOT neuro sxs)

Increased plasma homocysteine

Decreased plasma methionine

Increased methylmalonic acid*

245
Q

Vitamin B12 (Cobalamin)

Populations at risk for deficiency (5)

A 
Pernicious anemia
Gastric atrophy
Resection of stomach or ileum (intrinsic factor secretion/absorption)
Strict vegan diet
Breastfed infant of B12 deficient mother
246
Q

Vitamin B6 (Pyridoxine)

Function + two enzymes it is a cofactor for

A

amino acid metabolism, interconversions

Cofactor for cystathionine synthase (methionine/cysteine metabolism)

Cofactor for ALA synthase (first step in heme synthesis)

247
Q

Vitamin B6 (Pyridoxine)

Dietary sources (3)

A

animal products, vegetables, whole grains

248
Q

Vitamin B6 (Pyridoxine)

Deficiency findings (6)

A 
Anemia
seizures
glossitis
\+/- depression
-Increased serum homocysteine
-Increased serum methionine

NO MEGALOBLASTIC ANEMIA (differentiate with B12 and folate)

249
Q

Vitamin B6 (Pyridoxine)

Risk for deficiency (3)

A

Isoniazid (INH)**
end stage renal disease
malabsorption

250
Q

Vitamin B6 (Pyridoxine)

Toxicity

A

risk of toxicity at doses > 500 mg/d → sensory ataxia, impaired position/vibratory sensation

251
Q

Vitamin C (Ascorbic Acid)

Function (4)

A

Antioxidant/reducing agent
Collagen synthesis
Reduction of Fe3+ → Fe2+
NE synthesis

252
Q

Vitamin C (Ascorbic Acid)

Dietary sources

A

absorption maxes out → divide in <1g dose throughout day

Fruits, vegetables (broccoli, green pepper, citrus, potatoes)

253
Q

Vitamin C (Ascorbic Acid)

Deficiency findings

A

Scurvy: defective collagen formation

  • Painful joints**
  • Hemorrhagic signs - bleeding gums, ecchymoses, petechiae
  • Hyperkeratosis of hair follicles
254
Q

Dietary sources of iron (5)

A

cellular animal protein (heme iron), legumes, nuts, whole grains, green leafy vegetables

255
Q

More absorbable: heme iron (animal) or non heme iron?

A

Absorption of heme iron (animal protein) > nonheme iron

256
Q

Main site of iron regulation

A

intestinal absorption

257
Q

Things that decrease the absorption of iron (7)

A
  1. Phytate (bran, oats, beans, rye)
  2. Calcium
  3. Polyphenols (tea, some vegetables)
  4. Dietary fiber
  5. Soy protein
  6. Excessive Zn or Cu*
  7. Inflammation
258
Q

How does inglammation decrease absorption of iron?

A

Inflammation → increased hepcidin from liver → decrease absorption of Fe at enterocyte*

259
Q

Increase absorption of iron (2)

A
  1. Fe deficiency

2. Ascorbic acid (Vit C): Fe3+ → Fe2+ → more absorption of Fe2+

260
Q

Who is the cutest dog ever?

A

Bosco

JK it’s MUFFIN!

261
Q

Transportation of iron

A

Transferrin → transport (iron does not travel freely)

262
Q

Storage of iron

A

Ferritin

263
Q

Hemosiderin

A

aggregated ferritin molecules

264
Q

Most storage of iron in (3)

A

liver, bone marrow, spleen

265
Q

Hepsidin

A

decreases iron uptake, present during times of inflammation

266
Q

Function of iron (3)

A

oxygen transport in blood (Hgb) and muscle (myoglobin), electron transfer enzymes (cytochromes), CNS myelination

267
Q

Severe iron deficiency—>

A

oxygen transport in blood (Hgb) and muscle (myoglobin), electron transfer enzymes (cytochromes), CNS myelination

268
Q

Mild iron deficiency—->

A

anemia (microcytic, hypochromic, high RDW), **impaired cognitive development (can happen before anemia develops, and can have lifelong effects), decreased exercise tolerance, fatigue

269
Q

8 risks for iron deficiency

A
  1. Premature/SGA infants
  2. Breastfed infants (> 6 months)
  3. Young children - poor intake, increased requirements
  4. Adolescent girls/young women - menstrual loss
  5. Pregnant women → increased requirement
  6. Blood loss
  7. Obesity
  8. Bariatric surgery
270
Q

Iron deficiency pathophysiology

A

Iron is prioritized to erythrocytes because of role in O2 transport

Hepatic stores, skeletal muscles and intestine, cardiac iron, brain iron and finally erythrocyte iron depleted

271
Q

Labs iron deficiency

A

Low serum Fe, high TIBC, low % saturation, low ferritin

Microcytic, hypochromic RBCs

Low Hb and Hct

272
Q

Iron toxicity

A

Iron can act as PRO-OXIDANT

Deposition as hemosiderin in reticuloendothelial cells

Hereditary hemochromatosis

273
Q

Dietary sources of zinc

A

animal products, whole grains, legumes, seeds

274
Q

Bioavailability of zinc (3)

A
  • Absorption impaired by phytate (corn, legumes, nuts)
  • Absorption NOT increased with deficiency (unlike iron)
  • Can absorb/secrete Zn in GI tract
275
Q

Nutrition related 2015 Sustainable Development Goals (6):

A

1) Stunting - 40% reduction in number of children under five who are stunted
2) Anemia in women - 50% reduction of anemia in women of reproductive age
3) Low birthweight - 30% reduction of low birth weight
4) Overweight - no increase in childhood overweight
5) Exclusive breastfeeding - increase rate of breastfeeding in first 6 months up to at least 50%
6) Wasting - reduce and maintain childhood wasting to < 5%

276
Q

Contextual factors that contribute to malnutrition

A 
Lack of capital
Social, economic, political context
Poverty, food insecurity, unhealthy household, environment, inadequate care
Inadequate intake
Disease
Maternal and child undernutrition
277
Q

Major nutrition problems in developing countries:

A

Undernutrition in pregnancy (maternal undernutrition, BMI < 18.5) → fetal growth and postnatal growth → stunting, obesity, non-communicable diseases in adulthood

Vit A and Zn deficiencies → death, largest disease burden among micronutrients

Iron and iodine (+stunting) → children fail to reach developmental potential

Maternal overweight and obesity → maternal morbidity, preterm birth increased infant mortality

278
Q

Triple burden of poverty

A

diarrhea, stunting, chronic disease

279
Q

4 approaches to improving nutritional status in vulnerable populations:

A

1) Country level - individual country nutrition strategies and programs
- Draw on international evidence of good practice
- Must be country “owned” and built on country’s specific needs/capacity

2) Scale up evidence based cost effective interventions to prevent and treat undernutrition
Priority to first “1000 days” crucial window or highest return on investment-1000 days between woman’s pregnancy and child’s 2nd bday

3) Multi-sectoral approach - integrate food security (agriculture), social protection (including emergency relief), and health (maternal and child health care, immunization, family planning)
4) Scale up domestic and external assistance for country-owned nutrition programs and capacity

280
Q

BMI definitions:

normal
overweight
obese
severely obese

A

kg/m^2

BMI = 18.5-25.9 = Normal

BMI 25-29.9 = overweight → increased morbidity, but not mortality

BMI > 30 = obese

BMI > 40 or BMI > 35 + weight-related medical complications = Severe obesity

281
Q

BMI isn’t an accurate measurement for who? (2)

A

BMI is not an accurate measurement for people that are very muscular, or people who have lost large amounts of muscle mass but have clinically important obesity (e.g. elderly, “sarcopenic obesity”)

282
Q

Causes of malnutrition

A

protein malnutrition is the final common pathway, but energy requirements (president) trump ALL

Malnutrition secondary to chronic disease or due to acute effects of surgery, trauma, sepsis, etc. is estimated to occur in up to 50% of hospitalized patients

Anorexia nervosa

Poverty, ignorance, monotonous/restricted diets

283
Q

Consequences of malnutrition

A
  • “Failure to Thrive” - infants/children with growth faltering
  • Undernutrition
  • Stunting
  • Wasting
284
Q

Cause of obesity

A

changes in environment for food and physical activity

Long term positive energy balance

Gene-environment interaction

285
Q

Metabolic Syndrome

A

specific body phenotype of abdominal obesity associated with a group of metabolic disorders that are risk factors for CVD (CAD, stroke, CHF)

→ abdominal obesity, elevated BP, high TG, low HDL, impaired glucose tolerance

286
Q

Metabolic Syndrome

requirements (5)

A

Definition using AHA/NCEP: ⅗ risk factors = dx of metabolic syndrome

1) Abdominal obesity: waist circumference
Men = > 40 inches)
Women = > 35 inches

2) Triglycerides FASTING, > 150 mg/dL or on drug tx for abnormal lipids

3) HDL cholesterol:
- Men < 40 mg/dL
- Women < 50 mg/dL

4) Blood pressure: > 130 mmHg systolic or > 85 mmHg diastolic or on anti-HTN drug
5) Fasting glucose: > 100 mg/dL or hypoglycemic drug

287
Q

Clinical evaluation of obese patient

A

1) Measure degree of adiposity
2) Assess other existing risk factors for CVD
3) Screen for complications of obesity
- Labs: TSH, diabetes screening (fasting glucose, A1c), lipid panel, LFTs
4) Rule out medical causes of obesity
5) Assess readiness for treatment

288
Q

Health problems associated with obesity:

huge list……..

A

Cardiovascular: CAD, hyperlipidemia, HTN, CHF, stroke, venous thromboembolism

Pulmonary: obstructive sleep apnea, obesity-hypoventilation syndrome, asthma

Psychological: depression, social stigmatization, low self-esteem, distorted body image

Gastrointestinal: cholelithiasis, GERD, nonalcoholic fatty liver disease

Dermatological: acanthosis nigricans, cellulitis, striae, lymphedema, venous stasis

Orthopedic: osteoarthritis, restricted mobility, back pain

Genitourinary: PCOS, ED, BPH, menstrual abnormalities, infertility, pregnancy complications, stress incontinence

Metabolic: T2D, impaired glucose tolerance, gout, insulin resistance, metabolic syndrome, hyperuricemia, vit D deficiency, nephrolithiasis

Cancer: postmenopausal breast, colon, prostate, endometrial, kidney, gallbladder

289
Q

Function of zinc

A

regulation of gene expression (zinc fingers), zinc metalloenzymes,
structural role in membrane stability, metalloenzymes (>200!)

  • Critical for growth, cellular tissue proliferation, and immune function
  • Antioxidant
  • Sexual maturation
290
Q

Severe zinc deficiency

A

acro-orificial dermatitis, diarrhea

  • Increased infections, poor wound healing
  • Delayed sexual maturation
  • Acrodermatitis enteropathica: mutation in enterocyte Zn transporter → fatal without high doses of Zn for life
291
Q

Acrodermatitis enteropathica

A

mutation in enterocyte Zn transporter → fatal without high doses of Zn for life

292
Q

Mild zinc deficiency

A

growth retardation, anorexia, increased infection

293
Q

Zinc deficiency in fetus

A

intrauterine growth retardation, congenital malformations

294
Q

High risk individuals for zinc deficiency (7)

A
  • Infants, young children, breastfed infants (> 6 months)
  • Zn in breast milk is independent of mom’s Zn status
  • Pregnant women (high demand)
  • Monotonous, plant based diets
  • Bariatric surgery patients
  • Elderly (low intake)
  • GI illness/injury (diarrhea increases loss)
  • Wounds, burns (increased requirement for synthesis of new tissue)
295
Q

Zinc toxicity

A

impairs absorption of Fe and Cu, no real toxicity effects

296
Q

Presentation of kwashiorkor (8)

A

higher mortality than marasmus

  1. “Flaky paint” skin lesions
  2. “Flag sign” hair texture and pigmentation changes
  3. Generalized edema (“moon facies”)
  4. Hypoalbuminemia + enlarged fatty liver (hepatomegaly) → edema
  5. Increased permeability of biological membranes → edema
  6. Impaired Na/K homeostasis (excess Na, K deficiency)
  7. Hypotransferrinemia (anemia)
  8. Impaired immune system (infection)
297
Q

Consequences of malnutrition

A
  • “Failure to Thrive” - infants/children with growth faltering
  • Undernutrition
  • Stunting
  • Wasting
298
Q

Stunting (like my daddy)

A

chronic malnutrition, harder to treat

https://www.youtube.com/watch?v=jSPa3c41Or4

299
Q

Wasting

A

acute malnutrition - decreased weight relative to length

300
Q

Determining percentile for a kid

A

take weight and length, divide by normal (e.g. severely wasted child wt/ht → 7, normal → 10 = 70% ideal body weight)

301
Q

Short term events in starvation

A

decrease glucose, start kicking in with gluconeogenesis and fatty acid oxidation with ketone body formation → use fat stores, minimize muscle wasting → DECREASED basal metabolic rate

302
Q

Short term starvation: Muscle

A

Increase utilization of TGs/FAs, decrease protein degradation

303
Q

Short term starvation: Brain

A

increase utilization of ketones

304
Q

Short term starvation: Liver

A

decreased gluconeogenesis

305
Q

Short term starvation: Liver/Kidney

A

decreased urea production and excretion

306
Q

Long term effects of starvation (4)

A
  • Reduction in energy expenditure, decreased Na/K pump activity
  • Decreased inflammatory response and impaired immune function
  • Impaired function of GI tract
  • EVENTUALLY → loss of functional reserve and loss of physiological responsiveness to stress = HALLMARKS of adaptation to severe PEM
307
Q

Marasmus

A

severe wasting of fat and muscle mass due to energy deficiency (starvation)

  • Slower onset, better adaptation

Aka severe acute malnutrition

308
Q

Kwashiorkor

A

edematous PEM (with hypoalbuminemia), without wasting due to protein deficiency (not deficiency in total calories)

  • Rapid onset, “maladaptation”
309
Q

Pathophysiology of kwashiorkor

A

failure of normal adaptive response of protein sparing that is normally seen in fasting state

  • Protein deficiency in face of adequate energy intake PLUS infectious stress, cytokine release, relative micronutrient deficiencies, free radical exposure
  • Fat reserves and muscle mass unaltered (due to elevated insulin)
310
Q

Presentation of kwashiorkor (8)

A

higher mortality than marasmus

  1. “Flaky paint” skin lesions
  2. “Flag sign” hair texture and pigmentation changes
  3. Generalized edema (“moon facies”)
  4. Hypoalbuminemia + enlarged fatty liver (hepatomegaly) → edema
  5. Increased permeability of biological membranes → edema
  6. Impaired Na/K homeostasis (excess Na, K deficiency)
  7. Hypotransferrinemia (anemia)
  8. Impaired immune system (infection)
311
Q

Marasmic kwashiorkor

A

combination of chronic energy deficiency and chronic or acute protein deficiency

Presents with both wasting and edema

312
Q

Treatment of severe PEM

A

GO SLOWLY
1) Resolve life threatening conditions

2) Restore nutritional status without abruptly disrupting homeostasis
3) Ensure nutritional rehabilitation

313
Q

Resolving life threatening conditions in PEM (4)

A
  • Enteral rehydration (avoid overhydration)
  • K+ supplements +/- Mg2+ (avoid excessive Na+)
  • Treat infections
  • Avoid hypoglycemia with small, frequent, oral feeds
314
Q

Restoring nutritional status without abruptly disrupting homeostasis in PEM

A
  1. Small frequent feeds, liquid oral or nasogastric tube
    - Goal is to maintain protein and energy requirements
    - High protein, high fat
  2. Replete specific micronutrient deficiencies
315
Q

Ensuring nutritional rehabilitation in PEM (3)

A
  1. Slowly advance energy intake to 1.5x normal and 3-4x protein
  2. Begin AFTER resolution of edema
  3. Emotional and physical stimulation
316
Q

Refeeding syndrome

A

metabolic derangements due to acute shifts from ECF to ICD

317
Q

4 metabolic derangements that occur with re-feeding syndrome

A
  1. Potassium: increase insulin secretion → glucose and K+ IN to cells → decrease serum K+ → altered nerve/muscle function
  2. Phosphorus: increased insulin secretion → P IN to cells → increase intracellular phosphorylated intermediates → P “trapped” in intracellular space
  3. Magnesium: increased requirements with increased metabolic rate (cofactor for ATPase)
  4. Thiamine: rapid depletion → cardiomyopathy +/- encephalopathy

DEMS (10 decks)

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