Biochem metabolism Flashcards
1
Q
ATP is carrier molecule for what
A
phosphoryl groups
2
Q
NADH, NADPH, FADH2 is carrier molecule for what
A
electrons
3
Q
Coenzyme A, lipoamide is carrier molecule for what
A
Acyl groups
4
Q
Biotin is carrier molecule for what
A
CO2
5
Q
THF is carrier molecule for what
A
1 carbon units
6
Q
SAM is carrier molecule for what
A
CH3 groups
7
Q
TPP is carrier molecule for what
A
aldehydes
8
Q
What processes is NADPH used in? why?
A
anabolic processes (steroid & FA synthesis) to reduce equivalents;
Respiratory bursts;
p-450;
Glutathione reductase
9
Q
What is NADPH a product of?
A
HMP shunt
10
Q
what are the universal electron acceptors?
A
Nicotinamides (NAD+ from vitB3 & NADP+) & flavin nucleotides (FAD+ from vit B2);
NADPH
11
Q
What processes is NAD+ used in?
A
Catabolic processes to carry reducing equivalents away as NADH
12
Q
Describe the 1st step in glycolysis & 1st step of glycogen synthesis in the liver. what is the result?
A
phosphorylation of glucose to G-6-P via hexokinase or glucokinase
traps glucose inside the cell
13
Q
Describe where, speed and what leads to use of hexokinase
A
ubiquitous w/ high affinity (low Km), low capacity (low Vmax)
UNINDUCED by insulin
inhibited by G-6-P
14
Q
Describe where, speed and what leads to use of glucokinase
A
Liver & Beta cells of pancreas use GLUT-2 which has low affinity (high Km), high capacity (high Vmax)
INDUCED by insulin
High Vmax bc it cannot be satisfied
15
Q
Describe how glucose is sequestered dependent on its concentration
A
At low glucose (low insulin) then hexokinase sequesters glucose into the tissue;
At high glucose, excess glucose is stored in the liver
16
Q
Where does glycolysis occur?
A
cytoplasm
17
Q
Since RBC’s use glycolysis only, What will occur if the MC enzyme deficiency is present?
A
Pyruvate kinase deficiency will decrease pyruvate along w/ leading to hemolytic anemia due to the cell swelling & increased bilirubin
18
Q
Gluconeogenesis & Glycolysis are regulated by what?
A
F-2,6-BisP & PFK-2
19
Q
The pyruvate DH complex contains 3 enzymes that require 5 cofactors - name them
A
1) pyrophosphate (B1, thiamine (TPP))
2) FAD (B2, riboflavin)
3) NAD (B3, niacin)
4) CoA (B5, pantothenate)
5) Lipoic acid
20
Q
Other than the fed state, what else activates the pyruvate DH complex? what is the result?
A
exercise leads to
increased NAD+/NADH ratio
increased ADP
increased Ca+
21
Q
What 2 complexes use the same cofactors w/ similar substrate & action?
A
Pyruvate DH complex to make Acetyl-CoA & alpha-KG DH complex in TCA cycle to make succinyl-CoA
22
Q
What poison will damage the pyruvate DH & alpha-KG DH complexes? what is the result?
A
Arsenic inhibits lipoid acid leading to vomit, rice water stools, garlic breath
23
Q
If you have a muscle Bx that reveals increased glycogen, increased F-6-P & decreased pyruvate, what is the cause?
A
deficiency in PFK-1
24
Q
What are the enzymes responsible for increased & decreased levels of F-2,6-BP?
A
PFK-2 increases
FBP-2 decreases
25
Describe how a SANS response will change F-2,6-BP in the liver & muscle
Liver levels will decrease thus decreasing glycolysis
| Muscle levels will increase to activate PFK-1 to increase glycolysis
26
Pyruvate DH complex deficiency will lead to a backup of what? result?
pyruvate & alanine resulting in lactic acidosis
27
What are most cases of Pyruvate DH complex deficiency due to? What are the findings?
XL gene for E1-alpha subunit of PDC causing neuro defects that typically start in infancy
28
Acquired Pyruvate DH complex deficiency can come from what?
Arsenic poison;
| Decreased in B vitamins especially thiamine
29
What is the Tx for Pyruvate DH complex deficiency?
increase intake of ketogenic nutrients such as HIGH FAT content or increased lysine (dairy, fish) & leucine (eggs, soy)
30
What are the 4 products & cofactors of pyruvate metabolism?
Alanine via Alanine aminotransferase, B6;
Oxaloacetate via pyruvate carboxylase, biotin;
Acetyl-CoA via Pyruvate DH (B1-3,5, Lipoic acid);
31
During pyruvate metabolism, What processes occur in the cytosol? Mitochondria?
Alanine & lactate are produced in cytosol;
| Oxaloacetate & Acetyl-CoA are produced in the mitochondria
32
Where does the TCA cycle reactions occur?
Mitochondria
33
ETC & oxidative phosphorylation has a main function of what?
put H+ into inter membrane space to use as a gradient to power ATPase
34
What drug(s) inhibits complex 1 of ETC?
rotenone, barbituates, amytal, MPTP (synthetic demorol) => parkinson cause
35
What drug(s) inhibits complex 3 of ETC?
Antimycin A
36
What drug(s) inhibits complex 4 of ETC?
Cyanide, CO, NH3-, H2S
37
What drug(s) inhibits complex 5 of ETC?
Oligomycin
38
What drug(s) inhibits CoQ of ETC
Doxorubicin
39
Name ETC inhibitors along w/ action
rotenone, CN, antimycin A, CO => Directly inh electron transport leading to decreased proton gradient & ATP synthesis block
40
Name ATP synthase (complex 5) inhibitors along w/ action
Oligomycin=> directly inhibits mitochondrial ATPsynthase leading to increased proton gradient => NO ATP PRODUCED bc electron transport stops
41
Describe how uncoupling agents affect the ETC
increase permeability of inner Mt membrane leading to decreased proton gradient & increased O2 consumption => ATP synthesis stops but electron transport continues so HEAT IS PRODUCED
42
What are uncoupling agents of ETC?
2,4 DNP (wood preserver);
Aspirin (overdose fever);
thermogenin (brown adipose - baby fat)
43
What are the irreversible enzymes of gluconeogenesis? name location & substrate/product
pyruvate CB in Mt (biotin, ATP, acetyl-CoA)= pyruvate to OAA;
PEP CB in cytosol (GTP) = oxaloacetate to phosphoenolpyruvate;
F-1,6-BPase in cytosol = F-1,6-BP to Fructose-6-P;
G-6-Pase in ER = Glucose-6-P to glucose
44
Where does gluconeogenesis occur primarily? where can it not occur?
occurs in liver
cannot in muscle bc it has no G-6-Pase
45
What type of FA chains can serve as glucose sources? Why?
Odd bc yields 1 propionyl-CoA during metabolism to enter TCA (succinyl-CoA) to undergo gluconeogenesis
Even only yield acetyl-CoA so cannot make new glucose
46
What is the purpose of the HMP shunt?
provide NADPH from G-6-P for reductive rxn then produces ribose for nucleotide syn & glycolytic intermediates
47
Where do the 2 phases of HMP shunt occur? what is the difference in them?
Oxidative is irreversible using G-6-P DH (rate limiter) & NADP+to produce CO2, NADPH, Ribulose-5-P for PRPP generation for nucleotide syn
Nonoxidative is reversible & requires Thiamine & transkelotases to produce ribose-5-P, G3P, F6P
48
What cells can use respiratory burst (oxidative burst)? What is involved?
Neutrophils & monocytes activate membrane bound NADPH oxidase for immune response & release of ROI
49
What are the basic roles of NADPH?
create AND neutralize ROIs
50
Where in the neutrophil or monocyte does respiratory burst occur?
Phagolysosome
51
What is the result if NADPH oxidase is deficient?
chronic granulomatous disease
52
How does a WBC of pt w/ chronic granulomatous disease make ROI?
utilize H2O2 that is generated by invading organism (bacterial catalase) & convert it to ROI
53
If a patient is deficient in G6PD or NADPH oxidase, what type of infection risk is present?
catalase positive (S. aureus, Aspergillus) bc they neutralize own H2O2 leaving WBCs w/o ROI to fight infection
54
What is the MC human enzyme deficiency? How is it inherited & who shows the most prevalence?
XLR of G6PD deficiency that is MC in blacks assoc w/ increased malarial resistance
55
What is the result of G6PD deficiency in RBCs?
NADPH is decreased so cannot keep glutathione reduced therefore free rad & peroxides occur leading to damage & hemolytic anemia
56
What will be seen on a blood smear in a pt w/ G6PD deficiency?
Heinz bodies => oxidized Hgb precipitated w/in RBCs
| Bite cells result from splenic macs taking out heinz bodies thus leading to hemolytic anemia
57
What can induce a person w/ G6PD deficiency leading to hemolytic anemia?
fava beans (mediteranean food); sulfonamides, Primaquine, anti-TB; infection
58
Essential fructosuria has a defect in what and how is it inherited? What will diagnose & what Sx?
AR benign defect in fructokinase will lead to fructose in blood & urine
rare osmotic diarrhea
59
Fructose intolerance has a defect in what and how is it inherited?
AR deficiency in aldolase B leading to accumulation of F1P which binds phosphate resulting in inhibition of glycogenolysis & gluconeogenesis
60
Sx & Tx for fructose intolerance?
Sx are hypoglycemia, jaundice, cirrhosis, vomit;
| Tx is to decrease intake of both fructose & sucrose (glucose+fructose)
61
How does fructose bypass rate limiting step in glycolysis (PFK)?
aldolase B enzyme to yield glyceraldehyde & dihydroxyacetone-P
62
What type of sugar is galactose?
monomer sugar
63
Name enzyme & inheritance of galactokinase deficiency. What are the Sx of the deficiency?
AR deficient galactokinase leads to accumulation of galactitol if galactose is in the diet but will appear in blood & urine
may present as failure to track objects or develop social smile due to infantile cataracts
64
Name enzyme & inheritance of classic galactosemia. What causes the damage?
AR absence of galactose-1-phosphate uridyltransferase that leads to accumulation of toxins such as GALACTITOL that accumulates in lens of eye
65
Sx & Tx of classic galactosemia
Sx are failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation
Tx must exclude galactose & lactose (galactose + glucose) from diet
66
What is the most serious defects in classic galactosemia?
PO4 depletion
67
What enzyme other than G6P can trap glucose in the cell? how?
aldose reductase converts glucose to sorbitol (alcohol relative)
68
Once sorbitol is trapped within the cell, what occurs so it can be used for energy metabolism?
sorbitol DH converts it to fructose
69
Tissues that have insufficient amount of sorbitol DH are at risk for what?
osmotic damage due to accumulation leading to cataracts, retinopathy, peripheral neuropathy as in chronic hyperglycemia of diabetics
70
A patient w/ galactokinase deficiency will use what enzyme to make its damaging toxic metabolite?
High galactose uses aldose reductase to convert to galactitol that will accumulate in the eye
71
What tissues have both aldose reductase & sorbitol DH? What enzyme would have to be deficient to cause osmotic damage?
Liver, ovaries, seminal vesicles => sorbitol DH
72
What tissues have ONLY aldose reductase?
Schwann cells, retina, lens, kidneys
73
What type of sugar is lactose? what makes it?
disacaridase made of glucose & galactose
74
What are the causes of lactase deficiency?
Age dependent loss in enzyme;
hereditary lactose intolerance (AA, asians);
gastroenteritis due to temporary loss of microvilli
75
What are the Sx & Tx for lactase deficiency?
Sx are bloating, cramps, osmotic diarrhea
Tx is to avoid dairy products or add lactase pills to diet
76
Where is lactate used?
energy molecule that goes to liver cytoplasm for glucose to go to skeletal muscle via the Cori cycle
77
Give the essential amino acids and what they produce
glucogenic=> Met, Val, His
Gluco/Keto-genic => Ile, Phe, Thr, Trp
Ketogenic => leu, Lysine
78
What amino acid is targeted by oral HSV?
lysine
79
What are the acidic amino acids?
Aspartate & glutamate => negative at body pH
80
What are the basic amino acids? which has no charge at body pH
Arginine, Lysine, Histidine
His has no charge at body pH
81
Which amino acids are required during periods of growth?
arginine & histidine
82
Which amino acids are increased in histones? why?
Arginine & lysine so the negative charge DNA can bind
83
What is the rate limiting enzyme of urea cycle? where is it located?
CPS 1 located in mitochondria
84
Other than CPS 1, what other enzyme is found in the mitochondria?
ornithine transcarbamoylase in the conversion of ornithine to citrulline
85
What is the function of the urea cycle? What amino acids are necessary to carry it out?
Amino acids break down to pyruvate, acetyl-CoA so nitrogen must be excreted to avoid excess so converted to urea
Aspartate donates NH4 while Arginine is final step before urea is made
86
What molecule is essential for communicating anaerobic metabolism?
lactate
87
Amino transferases (ALT, AST) require what?
vitamin B6
88
Hyperammonemia occurs how? what are the results?
acquired via liver dz or hereditary via urea cycle deficiencies => results in excess NH4 that depletes a-KG leading to inhibition of TCA cycle
89
Sx of ammonia intoxication?
Hepatoencephalopathy
tremor (asterixis), slurred speech, somnolence, vomit, cerebral edema, blurring of vision
90
Tx for hyperammonemia
limit protein in diet & benzoate or phenylbutyrate can be given to decrease ammonia levels;
lactulose
91
How does benzoate or phenyl butyrate treat hyperammonemia?
both bind amino acid & lead to excretion
92
How does lactulose treat hyperammonemia?
it is a sugar that is not absorbed so gets to colon & bacteria there have a feast thus making the colon acidic causing binding of the NH4+ for excretion
93
What is the MC urea cycle disorder? How is it inherited? When does it present?
ornithine transcarbamoylase deficiency is XLR presenting in first few days of life but can present later
94
What are the labs of OTC deficiency?
excess carbamoyl phosphate in mitochondria spills out & is converted to orotic acid (part of pyrimidine synthesis)
increased orotic acid in blood & urine, decreased BUN, Sx of hyperammonemia (tremor, vomit, somnolence, cerebral edema)
95
Differentiate OTC deficiency vs orotic aciduria
OTC deficiency is NOT associated w/ megaloblastic anemia
96
What are the derivates of phenylalanine?
(via BH4) tyrosine to make Dopa (vit B6) DA, (vit C) NE, (SAM) Epi
97
derivates of tryptophan
(vit B6) niacin to NAD+/NADP+
| (BH4) serotonin to melatonin
98
derivates of histidine
(vit B6) histamine
99
derivates of glycine
(via B6) porphyrin to heme
100
derivates of arginine
creatine;
urea;
(BH4) nitric oxide
101
derivates of glutamate
(via B6) GABA;
| glutathione
102
What amino acid derives melanin? How?
phenylalanine (BH4) to tyrosine to (BH4) Dopa which is converted to melanin
103
What amino acid derives thyroxine?
Phenylalanine via BH4 to tyrosine to thyroxine
104
derivates of methionine
SAM
105
What are the respective breakdown products of catecholamines? how are they broken down?
MAO & COMT breaks down
DA to HVA
NE to VMA
Epi to metanephrine
106
What is the etiology of PKU? What will be found in urine?
AR decrease in phenylalanine hydroxylase (adds OH) or decrease in BH4 (malignant PKU)
phenylketones in urine (phenylacetate, phenyllactate, phenylpyruvate)
107
When does PKU typically present & earliest signs?
2-3 days after birth bc uses mother's enzyme during fetal life
musty odor due to aromatic AA metabolism
108
Findings of child with PKU
```
mental & growth retardation;
seizures;
fair skin;
eczema;
musty odor
```
109
Treatment of PKU
decrease Phe in diet (NO aspartame ~ nutrasweet)
Increase tyrosine (essential AA now)
Must be done w/in first 3 wks
110
Maternal PKU can occur how? what are the findings in the child?
lack of proper diet during pregnancy
microcephaly; growth & mental retardation; congenital heart defects
111
Pt notices urine turns black in the air & presents to ortho w/ debilitating joint pain. What is the disease caused by?
Alkaptonuria (ochronosis) =>
| AR congenital deficiency of homogentisic acid oxidase in degradation of tyrosine to fumarate
112
What are the findings of alkaptonuria?
dark connective tissue;
brown pigmented sclera;
urine turns black w/ air exposure;
May have debilitating arthralgias
113
What are the debilitating arthralgias of alkaptonuria from?
homogentisic acid being toxic to cartilage
114
What are the 2 causes of albinism?
congenital deficiency of:
tyrosinase (inability to synthesize melanin) => AR
Defective tyrosine transporters (decrease amounts of tyrosine & melanin)
115
During embryology, what also may cause albinism?
lack of migration of neural crest cells
116
Describe the inheritance pattern of albinism
variable inheritance due to locus heterogeneity
ocular albinism is XLR
117
What are the 3 forms of homocystinuria? How are they inherited & what is result?
ALL are AR resulting in excess homocysteine & cysteine is now essential amino acid
Cystathionine synthase deficiency
Decreased affinity of cystathioinine synthase for pyridoxal phosphate
Homocysteine methyltransferase deficiency
118
How is Cystathionine synthase deficiency treated?
decreased methionine;
| increase cysteine, B12 & folate, B6 in diet
119
How is Decreased affinity of cystathioinine synthase for pyridoxal phosphate treated?
increased a lot of vitamin B6 in diet
120
How is Homocysteine methyltransferase deficiency treated?
requires B12 so give it
121
What are the findings in homocystinuria?
```
lots of homocysteine in urine; mental retardation;
osteoporosis & tall stature;
kyphosis;
Lens subluxation (down & in);
atherosclerosis (stroke & MI)
```
122
What is the cause of cystinuria?
AR defect of renal tubular AA transporter for COLA (cysteine, ornithine, lysine, arginine) in the PCT of kidneys
123
How will cystinuria present? What is the Tx?
excess cystine in urine leads to precipitation of hexagonal crystals & renal stag horn calculi
Tx is good hydration & urinary alkalinization
124
What makes up cystine? How is a cystine stone treated?
2 cysteines connected by disulfide bone
if stone then Acetazolimide (diuretic) & hydrate
125
Maple syrup urine disease is caused by what? what are the labs for it?
AR defect causing blocked degradation of branched amino acids (Ile, Leu, Val) due to decrease in alpha-ketoacid DH (B1) leading to increased alpha-ketoacids in blood (esp Leu)
126
What does maple syrup urine disease cause?
severe CNS defects;
mental retard;
death
127
I Love Vermont maple syrup from maple trees with Branches
maple syrup urine disease
128
What causes Hartnup disease?
AR dz w/ defective neutral AA transporter on renal & intestinal epithelial cells
129
What is the result of Hartnup disease?
tryptophan excreted in urine & decreased absorption from gut
leads to pellagra ( decreased B3/niacin) => diarrhea, dementia, dermatitis
