Hormone Diseases 2

Front 1

CAT I defish

Back 1

FA's not transferred into mito matrix.
Carnitine can't become acylcarnitine, to be transported in.

Only long chain FAs (14-20)
Muscle weekeness

Front 2

CAT II defish

Back 2

acylcarnitine can't become Carnitine, to be transported out of mitoch matrix

(only long chain FAs)

Front 3

Fatty Liver & Cirrhosis

Back 3

+++ ethanol
--- NAD+ (not enough for FA ox)
-> FAs stay in liver -> cirrhosis

Front 4

Medium Chain Acyl Co A Dehydrogenase (MCAD)

Back 4

(MCAD breaks 6-12 C FAs)
Can't switch from glycolysis to Beta Ox)

Intolerance to prolonged fasting.
--ATP -> ++ hypoketotic hypoglycemia
Related to Reyes/SIDS

Rx: carb diet

Front 5

Hypoglycin A

Back 5

Unripe ackee fruit protein
-> inhibits acylcoA Dehydrogenase, and unable to break down AcylCoA

-> Jamaican Vomiting Sickness

Front 6

Alpha hydroxylase defish

Back 6

Unable to break down branch chain FAs
-> Refsum's disease
+++ phytanic acid

Alpha ox: acetyl co a and propionyl Co A are release alternately that can then go into TCA or glycolysis

Front 7

acyl co A synthase defish

Back 7

FA chains >22 broken down in peroxisomes (not brnach chains) (no CAT needed).

defish ->
Adrenoleukodystrophy (ALD)
+++ VLC FAs in blood
-> destroys myelin

Front 8

Zellweger syndrome

Back 8

No functional peroxisomes. So
+++ VLC FAs (>22)
Enlarged head, MR

Front 9

Hemochromatosis rxn:

Back 9

Fenton rxn: H2O2 + Fe2+ -> Oho + OH- + Fe3+
Superoxides generated in I, II, III of the ETC

Front 10

Gp91 defect

Back 10

Defect in NADPH oxidase: phagosome creation of O2o
+++ bacteria
Gp91 – X-linked disease
P222, p67, 47 autosomal

Front 11

Malon dialdehyde

Back 11

Malon dialdehyde: CHO-CH2-CHO
H202 attacks PUFA DBs, causing LIPID PEROXIDATION.
++Malondialdehyde

Front 12

Superoxide Dismutase disease

Back 12

ALS / Lou Gehrigs/ Motor Neuron Disease
1-2% = SOD1 stability problem
SOD1, SOD2 convert 2O2o -> H202
Repair enzymes in breakdown of superoxides

Front 13

NADPH Oxidase defish

Back 13

CGD Chronic Granulatomous Disease: aggregation of phagocytes
(Phagocytes unable to create superoxides to kill bacteria)
-- O2o, -- H2O2, -- HOCl
++ bacteria
NO: hemolytic anemia, jaundice vs G6PD defish: you do

Front 14

G6PD defish

Back 14

Unable to create NADPH (HMP) (so no e- donor)
Mild: no effect unless taking malarial/oxidative drug
Severe: phagocytes fail, and CGD-like symptoms WITH anemia, jaundice

Front 15

Unsat FA breakdown: isomerase and reductase defish

Back 15

isomerase: DB at 3=4 to 2=3
reductase: linoleic acid: brings two DBs to one, so isomerase can work on it

Front 16

Ketonemia

Back 16

detectable Ketones in plasma

starvation/diabetes:
---glycolysis
+++ lipolysis
-> --- OAA for TCA
-> +++ acetyl coa -> kbs

Front 17

Ketonuria

Back 17

detectable ketones in urine

Front 18

HMG CoA Synthetase Defish

Back 18

(acetyl acetyl coA -> Acetone, Ketone bodies)
Unable to oxidize FAs
+++ acetoacetyl Co A
--- Acetone/Ketone bodies

Front 19

Thiophorase defish

Back 19

Thiophorase NOT in liver, just peripheral tissues. therefore Ketone bodies can't be broken down in liver. (Liver: FAs to KBs, then periph tissues KBs -> TCA)

Thiophorase defish:
+++ ketone bodies (unable to be broken down

Thiophorase:
Succinyl CoA -> Acetoacetyl CoA + Succinate

Front 20

Cyclooxygenase defish (COX)

Back 20

Unable to create
Prostaglandins,
Thromboxanes,
Prostacyclins

From Arachidonic Acid

Front 21

Lipooxygenase defish (LOX)

Back 21

Unable to create
Leukotrienes,
HETES, and HPETEs

from arachidonic acid

Front 22

PLA2 defish

Back 22

Unable to convert PLs from PM into arachidonic acid

Front 23

Prostaglandin PGE2 causes

Back 23

+++ Vasodilation
+++ cAMP
--- aggregation

Front 24

Prostaglanding PGF2Alpha causes

Back 24

+++constriction: muscle, veins, broncho

Front 25

Prostacyclin PGI2 causes

Back 25

+++ Vasodilation
+++cAMP
--- platelet aggregation

Inhibited by Vioxx, causing heart attacks

Front 26

Thromboxanes TXA2

Back 26

--- Vasoconstriction
+++ aggregation

Front 27

Leukotrienes LTB, LTC, LTD

Back 27

+++ broncho constriction
--- vascular permeability
+++ aggregation

-> anaphylactic shock

Front 28

Steroidal Antiinflammatory drugs

Back 28

inhibits PLA2
--- ALL eicosanoids
e.g., cortisol, cortisone

Front 29

COX 1 defish

Back 29

--- Protection of stomach, kidney and clotting

Front 30

COX 2 defish

Back 30

--- inflammation, pain, fever, swelling

Front 31

Aspirin, Indomethacin, Ibuprofen

Back 31

COX 1 + COX 2 inhibitors (NSAIDS)
--- stomach, kidney, platelet protection
--- pain, inflammation

Aspirin transfers an acetyl group to COX, irreversibly inactivating it

Front 32

Viox, celebrex

Back 32

COX 2 inhibitors, not COX1
--- pain, swelling

Vioxx ++ PGI2 -> leading to heart attack, stroke

Front 33

Tylenol

Back 33

NSAID that targets COX 3:

--- brain pain

Front 34

Hartnup disease

Back 34

Netral AA fails: neutral AAs e.g., Trp cannot be transported into cell, and are excreted
--- Trp -> --- Niacin
-> Pellagra

Front 35

Val-Acyclovir

Back 35

Herpes medication. Ester (not peptide) bond. Transported across PEPT1 (peptide transporter) even though not peptides

Front 36

Beta-Lactam

Back 36

Antibiotic. Looks like a peptide. -> PEPT1 transports

Front 37

Cystinuria

Back 37

Defect in Cationic transporter. Unable to absorb:
Lysine, arginine, ornithine
AND cystine (two cysteines joined by a disulfide bond).
No intestinal problems as cationic peptides absd PEPT1
But Kidney unable to reabs cystin, lys, ornithine, arginine.
+++ cystine (not others) in urine >300mg/L -> kidney stones.
Rx: drink a lot

Front 38

Kwashiorkor vs Marasmus
Diet protein
Calories
Plasma AAs
Hypoalbuminemia

Back 38

Diet protein:
Kwash: low
Maras: low

Calories
Kwash: normal
Maras: low

Plasma AAs:
Kwash: Low
Maras: Normal (SKM is degraded since low cal)

Hypoalbuminemia
Kwash: yes
Maras: No: skm degraded so plasma aa's normal

Front 39

Kwashiorkor vs Marasmus

Edema
Growth retard
Fatty liver
Subcut fat

Glucagon/insulin levels

Back 39

Edema
Kwash: yes (low plasma AAs)
Maras: no (skm degraded, normal plasma AAs)

Growth retardation
Kwash, Maras: yes

Fatty liver
Kwash: yes
Maras: no (skm degraded, less ketone bodies)

Subcut fat
Kwash: yes (--- lipolysis)
Maras: no (low calories)

Kwash: looks healthy
Maras: looks sick

Kwash: +++ insulin
Maras: --- insulin

Front 40

Transaminase co-factor

Back 40

B6 / pyridoxin

Front 41

Transaminase/B6 defish

Back 41

Cannot convert AA to Ala/Gln to be sent to liver for breakdown

Front 42

Glutaminase defish

Back 42

Cannot break down Glutamine into Glutamate + NH3

Glutamine broken down in KIDNEY into NH4 (NH3 + H+)
LIVER: UREA

Front 43

Metabolic acidosis

Back 43

+++ glutamine in kidney
+++ NH3
-> H+ elimination

Front 44

Hepatic encephalopathy

Back 44

Pathology in brain originating in liver

Brain not converting NH3 + A-KG to Glutamine
Leads to hyperammonemia, mental retardation, protein intolerance

+++ NH3
-> --- A-KG
-> --- TCA
-> --- ATP

Front 45

Carbamoyl Phosphate Synthase I (CPS1) defish

Back 45

Type I hyperammonemia
(1st step in urea cycle: HCO3- + NH3 -> CP. ATP reqd. AA breakdown in mito)

+++ NH3, +++ Gln, +++ Ala
--- CP

note: type I hyperammonemia: +++ Ala. Type II Ala fine
Note:
--- uracil, orotic acid since --CP

Front 46

Ornithine Transcarbamoylase (OTC) defish

Back 46

Type II hyperammonemia
+++ orotic acid, uracil
--- urea

+++ NH3, Gln, CP
Note: Ala is fine: converted from CP to orotic acid!)

Front 47

Arginine Succinate Synthase defish

Back 47

-> Citrullinemia
(Citrullinne -> Arginine succinate ATP reqd. in cyto)

++NH3, Citrulline

So, CPSI and ASS require ATP to break down AAs

Front 48

Arginine Succinate Lyase

Back 48

Arginine Succinate Anemia
++ NH3, AS
(Arginine Succ -> Arginine)

Front 49

Phenylbutyrate

Back 49

Treats urea cycle disorders (hyperammonemia) by getting rid of glutamine (2NH3) in the urine

Phenyl butyrate is a type of phenyacetate (phenylacetate smells mousy, not phenylbutyrate).

Front 50

In the urea cycle, what is the main carrier of NH3

Back 50

A-KG. Takes 2 NH3s

Front 51

What are the ketogenic aa's? (Can be converted into Acetyl Coa)

Back 51

Leu, Lys

Ile, + Aromatics Phe, Tyr, Trp are both gluco and keto

Front 52

What enzymes require:
TPP -> Thiamine
FAD -> riboflavin
CoA -> pantothenic acid (B5)
NAD+ -> Niacin (B3)
Lipoic acid

Back 52

Branch Chain Dehydrogenase (Break down Val, Ile, Leu)
A-KGDH
PDH (Pyr -> OAA)

Front 53

Branch Chain Ketoacid Dehydrogenase Defish

Back 53

Maple Syrup urine disease
+++Val, Ile, Leu not broken down
+++ MR, Ketoacidosis, protein intol
RX: restrict Val, Leu, Ile. Need some!

Front 54

B12 Carboxylase co-factor

Back 54

Biotin
(except Gamma carboxylase, which requires Vita K)

Front 55

Proprionyl Carboxylase/Biotin Defish

Back 55

Val, Ile are Glucogenic. Leu is not.

Val/Ile -> Proprionyl CoA +CO2 -> Malonly CoA

Val, Ile affected:
+++ Proprionyl CoA -> proprionic acidemia

Rx: restrict Val, Ile
Give biotin

Front 56

What is the Methyl Malonyl Co A Mutase co-factor?

Back 56

B12

methyl malonyl -> succinyl co A

Front 57

Methyl Malonly Co A Mutase/B12 defish

Back 57

Val/Ile->>>> malonlyl CoA -> Succinyl Coa (glucogenic)

Val, Ile affected. Not Leu

++ methylmalonic acid
++ MR

Front 58

B12 Defish

Back 58

<- Vegan diet
<- gastrectomy
<- pancreatitis
<-pernicious, megaloblastic anemia

Front 59

Dihydropteridine reductase defish/ THB defish

Back 59

Phe X-> Tyr -> melanin
-> PKU:
-- melanin hypopigmentation (fair, blond)

++Phe -> pheny acetate/phenyl lactate
Phenyl acetate = mousy smell!)
++ Phe, Pyr in blood
-> --ATP
-> neutral aa's can't get into brain BBB

RX: Tyrosine supplement (not essential for normal people)

Front 60

Dhydropteridine reductase.

Back 60

=Classical PKU.
THB fine.
Only Phe affected
Diet therapy. give Tyr

Front 61

Atypical PKU

Back 61

THB defective. Diet does not work

Tyr -> Dopa -NE
Trp -> 5-OH-Trp -> Serotonin

-- Dopa, Serotonin, NE

RX: diet + Dopa, + 5OHTrp + THB

Front 62

Maternal PKU

Back 62

eating wrongly affects even heterozygous baby

Front 63

Aspartame/Equal Sugar

Back 63

Containe Phe. Bad for PKU patients

Front 64

Tyrosinase defish

Back 64

Phe ->Tyr X-> Dopa X-> Melanin

ALBINISM

Front 65

HGA Oxidase defish

Back 65

Alcaptonuria (urine turns black when encounters alkali)
-> arthritis @ 30

(Tyr -> Homogentistic acid X->)

Front 66

Homocysteinemia

Back 66

++ homocysteine
Cannot create methionine, or cysteine
-> collagen defects
1. glaucoma (occular)
2. osteoporosis (bone)
3. MI, stroke (vascular)

Could be due to B12, FolA, or B6 defish

Front 67

B12 defish

Back 67

megaloblastic anemia WITH ++ methyl malonic acid

Front 68

Folic Acid defish

Back 68

megaloblastic anemia WITHOUT
++ methyl malonic acid

Front 69

B6 defish

Back 69

microcytic anemia
WITHOUT
++ methyl malonic acid
(Homocysteine is converted to Methionine, since there is no B12 defish.)

Front 70

Methionine synthase defish
(cofactor)

Back 70

B12 and Fol A (THF) are co-factors

-> Homocysteinemia
(homocysteine -> methionine)
++ homocysteine
-- methionine

Megaloblastic anemia (++methyl malonic acid?: depends on B12 defish)

Front 71

Cystathione Beta Synthase defish
+ cofactor

Back 71

(homocysteine X-> cystathione -> cysteine)
B6 Pyridoxine

-> homocysteinemia
homocystein -> cystathione -> cystein

No ++ methyl malonic acid
Microcytic anemia (B6)

Front 72

Dipalmitolyphosphatidyl-choline (DPC)

Back 72

Phospholipid made by Type II pnemocytes, and needed for surfactant.

<2.0 Lecithin/sphingomyelin ratio:
->RDS

Front 73

Platelet activating factor

Back 73

Plasmalogen that causes
platelet aggregation
edema
hypotension, allergies

In heart, SK muscle

Front 74

Sphingomyelinase defish

Back 74

unable to degrade sphingomyelins
(sphingomyelin -> ceramide + phosphoryl choline)

defish:
++ sphingomyelins
e.g., Nieman pick

Front 75

Glycosphingolipds Form:

Back 75

Surface receptor e.g., Cholera toxin, Diphtheria
Blood group antigens (transfusions/transplant issues)
outer PM

Front 76

Beta Hexosaminadase A defish

Back 76

-> Tay Sachs
+++ GM2

-> blindness, hepatosplenomegaly, cherry spot on retina

Front 77

Hexosaminadase A and B defish

Back 77

Sandoff's

++ Globosides
Similar to Tay Sach's, but more rapidly progressing

Front 78

Glucosidase defish

Back 78

Gaucher's
++Glucocerebroside
hepatosplenomegaly
**MR

Front 79

Arylsulfatase A defish

Back 79

Metachromatic Leukodystrophy
++ Sulfogalatocerebroside
Demyelination
MR

Front 80

Beta Galactosidase defish

Back 80

Krabbe's
++ galactocerebroside
myelin absent
(generalized gangliosidosis also a Beta Galactosidase defish)

Front 81

Sphingomyelinase Defish

Back 81

Niemann Pick
++ sphingomyelin
Hepatosplenomegaly

Front 82

low urine estriol

Back 82

indicative of fetal death/retardation
placental sulfatase defish (placenta can't use sulfated steroids)

Front 83

placental sulfatase defish

Back 83

low maternal estriol, estradiol
icthyosis
Sulfatase is a marker for fetal fn

Front 84

Androgen insufficiency

Back 84

= androgen insensitivity
Normal linear growth
XY with female phenotypes
Androgen -> estrogen, so normal levels estrogen which produces somatic growth.

Front 85

IGF1 defish

Back 85

= growth hormone insensitivity
May be due to STAT5 problem, or JAK problem.

GH fine
--IGF1 => Shorter

Front 86

SRY problem

Back 86

Male gonadal sex stage broken
Male sertoli cells don't develop

Front 87

AMH/MIS defish

Back 87

Anti mullerian hormone/ Mullerian inhibiting substance

Responsible for loss of Mullerian duct.

Defish: mullerian duct stays (phenotypic stage)

Front 88

CYP11A1 defish

Back 88

CH -> Pregnenelone
Rate limiting Rxn, requires STAR

Front 89

17 beta HSD defish

Back 89

Hyperaldosteronism
-- testo, estro, cortisol

Unique to Leydig cells (create testo -- duh!)

Front 90

5 alpha reductase defish

Back 90

Testo -> DHT
External sex structure not created.
Note: testo does not create externals

Wolfian ducts present (testo present)
Mulerian ducts gone (AMH/MIS present due to testosterone)
Just no virilization and EXTERNAL structures

Front 91

inhibin defish

Back 91

+++FSH

inhibin feeds back to stop FSH secretion

Front 92

Loss of blood/testis barrier

Back 92

Blood testis barrier protects spermatocytes/spermatids (not gonia) from sperm antibodies, since they express foreign proteins.

Breakdown in BT barrier causes infertility

Front 93

fetal hCG defish

Back 93

hCG -> Leydig cells -> testo

no hCG, no testo

(vs at puberty: LH -> testo)