BIOCHEMISTRY Flashcards
Amino acids cannot be synthesized by the human body
Essential Amino Acid
Antibiotic that inhibits cell wall synthesis
Bacitracin
Antibiotic that interupt DNA and protein function
Gramicidin A
Dreaded side effect of bleomycin
Pulmonary fibrosis
Other drugs:
Busulfan
Amiodarone
Cyanobacterial peptides lethal (hepatic tumors) in large doses
Microcystin and nodularin
Neurodegenerative disease associated with chick pea and grass pea
Lathyrism
- paraplegia, tremors and muscular weakness
Seed contains neurotoxins risk factors for neurodegenerative diseases ALS and PD
Cycad seeds
Neurotoxic found in cycad seed - natives of Guam
Beta Methylaminoalanine
Potentially toxic L alpha amino acids
ODAP
BMAA
BAPN
Diaminobutyric acid
Homoarginine
Naturally occuring amino acids in brain tissue
Serine and aspartate
Naturally occuring amino acids in gram positive bacteria
Alanine and Glutamate
Bacteria with poly D glutamate capsule
B. anthracis
excretes D-methionine, D-tyrosine, D-leucine and D-trypttophan which triggers biofilm disassembly
B subtilis
Bacteria incorporates leucine and methionine into the peptide component of its peptidoglycan layer
Vibrio cholerae
Amino acid precursor of thyroid hormone
Tyrosine
Precursor of Tyrosine
Phenylalanine
Enzyme catalyzes phenylalanine to tyrosine
Phenylalanine hydroxylase
Neurotransmitter precursor of GABA
Glutamate (excitatory)
enzyme that catalyses glutamate to GABA
Glutamate decarboxylase
Determine classification of amino acid
Side chain
found at the center, attached to four different substituents. It confers optical activity
chiral carbon
Amino acid without chiral carbon. No optical activity. Cannot rotate plane polarized light.
Glycine
Stereoisomer
Enantiomers “mirror image”
Posttranslational modification of amino acid where proline and lysine –> 4 hydroxyproline and 5-hydroxylysine
Collagen synthesis
Posttranslational modification of amino acid where carboxylation of glutamyl residues to y- carboxyglutamyl residues
Blood coagulation cascade
vitamin or cofactor required for collagen synthesis
Vitamin C
Vitamin K dependent clotting factors
Factor 2, 7, 9, 10
Drug inhibits gamma carboxylation of vit K dependent clotting factors
Warfarin/ Coumadin
Warfarin inhibits what pathway?
Extrinsic pathway
W (warfarin) e(extrinsic)
Pt (protime)
condition with vitamin c deficiency
Scurvy
Triple helix structure with glycine-X-Y (proline or hydrodyproline)
Collagen
Molecules that contain an equal number of + and - charged groups bear no net change.
Dipolar ion
Zwitterions
Amino acids contains both acidic and basic group. at physiological pH (~7)
Amphoteric
Used to express the strength of weak acids
pKa
smaller pKa = stronger
larger pKa = weaker
Property of amino acids reflects their ionic character
Solubility
*tryptophan, tyrosine and phenylalanine (aromatic rings) absorb higher wavelenght ultraviolet light
Responsible for formation of esters, amides and acid anhydrides
Carboxylic acid groups
for acylation and esterification
Amino groups
smallest amino acid
glycine
Protein structure - peptide bond
Primary structure
Protein structure - Beta pleated sheets or Alpha helix
Secondary structure
Protein structure - Domains, salt bridges, myoglobin
tertiary structure
Protein structure - hemoglobin
Quaternary structure
Amino acids are linked together by?
Peptide bond
Presence of peptide test (violet in color)
Biuret test
Rate limiting enzyme of pentose phosphate pathway / HMP
Glucose 6 phosphate dehydrogenare
3 amino acids comprises structure of glutathione
glutamyl
cysteinyl
glycine
amino acids with alipathic side chains
Glycine (heme synthesis)
Alanine
Valine
Isoleucine
Leucine
Branched chain amino acid
Valine
Isoleucine
Leucine
congenital deficiency of branched chain amino acid
maple syrup disease
Hydroxyl group amino acid
Serine
Threonine
Tyrosine
amino acids with sulfur atoms
Cysteine
Methionine
1st amino acid in genetic code
Methionine
Amino acids with acidic groups
Aspartic acid
Asparagine
Glutamic acid
Glutamine
Basic amino acids
Histidine
Arginine
Lysine
Precursor of nitric oxide, urea cycle
Arginine
undergoes decarboxylation - Histamine
Histidine
Amino acid with aromatic ring
Phenylalanine
Tryptophan
Histidine
Tyrosine
Precursor of cathecholamines
Tyrosine
Precursor of vit B3 or niacin
Tryptophan
Amino acid with Imino group
Proline
-causes collagen kinks
Atypical amino acids
Pyrrolysine
Selenocycteine
21st amino acid
Selenocysteine
3 stop codons
UAG
UAA
UGA
Mutation when a stop codon is involved
Nonsense mutation
Essential amino acids
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Arginine
Leucine
Lysin
Always ARGues , never TYRs
Purely ketogenic amino acids
Leucine
Lysine
“KiLL”
Biochemical pathways occur in the mitochondria
Fatty Acid Oxydation
Acetyl CoA
TCA (Krebs cycle)
Oxydative Phosphorylation (Respiratory Chain/ ETC)
Mito FATO
Biochemical pathways occur in the Cytosol and Mitochondria
Heme
Urea
Gluconeogenesis
give BOTH of you a HUG
Where does glycolysis occur?
Cytosol
2 types of glycolysis?
Aerobic and anaerobic
End product of aerobic glycolysis
Pyruvate
End product of anaerobic glycolysis
Lactate
Rate limiting enzyme of glycolysis
Phosphofructokinase (PFK)
Glycogen storage disease with deficiency in Phosphofructokinase (PFK)
Type 7 - Tarui’s disease
Enzyme inhibited by Flouride
Enolase
Other name of glycolysis
Embden Meyerhoff Parnas Pathway
Metabolism of glucose to pyruvate/lactate
Glycolysis
First step in utilization of sugars
Phosphorylation of glucose
Found in most tissue
Low Km
Low Vmax
Hexokinase
H = Humble (low Km low Vmax)
What inhibits hexokinase
Glucose-6-phosphate
What inhibits glucokinase?
Fructose 6 phosphate
What stimulates glucokinase?
Glucose
Insulin
The most potent activator of Phosphofructokinase
Fructose 2, 6 bisphosphate
Well fed or starvation?
Dec glucagon
Inc insulin
Inc frictose 2,6 bisphosphate
Inc glycolysis
Well fed state
Cleaves fructose 1, 6 bisphosphate
Found in the liver and kidney
Aldolase B
Used in the liver and adipose tissue for triglyceride synthesis
Isomerized to become glyceraldehyde 3 phosphate
DHAP - Dihydroxyacetone Phosphate
Deficiency in aldolase B presents
Hemolytic anemia
MOA: competing with inorganic phosphate as substrate for G3P DEHYDROGENASE — complex that spontaneously hydrolyzes to form 3-phosphoglycerate
Arsenic poisoning
Mg or Mn dependent
Inhibited by flouride
Enolase
2nd most common cause of enzymatic related HEMOLYTIC ANEMIA
Pyruvate Kinase Deficiency
Most common cause of enzymatic related hemolytic anemia
Glucose 6 phosphate dehydrogenase deficiency (G6PD deficiency)
What enzyme catalyzes the first substrate level phosphorylation in glycolysis?
Phosphoglycerate kinase
What enzyme catalyze the irreversible reactions of glycolysis?
Hexokinase
Phosphofructokinase
Pyruvate kinase
Other names of Pentose Phosphate Pathway
Hexose Monophosphate Pathway/ Shunt
Phosphogluconate oxidative pathway
Warburg- Dickens Pathway
Products of Pentose Phosphate Pathway
NADP (2 generated per glucose6-P)
Ribose
Location of PPP
Cytosol
Rate limiting enzyme of PPP/ HMP
Glucose-6- Phosphate Dehydrogenase (G6PD)
Reactants of PPP
NADP
Glucose-6-P
Phases of PPP
- Oxidative - produce NADPH
- Non oxidative - Pentose sugars produced for nuclei cholesterol acid synthesis
Tissues with active Pentose phosphate pathway
RBC
Adrenal gland
Testes
Adipose tissue
Mammary gland
Pathways in mitochondrial matrix (3)
Kreb’s cycle
Urea cycle
B-oxidation
The only thiamine enzyme in the RBC that is needed for interconversion of sugars
Transketolase
NADPH functions (4)
- Biosynthesis of FA and steroids
- Supply of Reduced Glutathione
- Bactericidal (respiratory burst)
- Liver microsomal cytP450
What immune deficiency arises with defective respiratory burst?
CGD
Chronic Granulomatous Disease
“Lacks respiratory/oxidative burst”
Recurrent pyogenic infection + granuloma
NADH is important for
ATP Production
NADPH is important for
Reductive biosynthesis
Reduced form of NADP
NADPH
Deficiency of G6PD causes?
Favism
Fava beans - mediterranean diet
Converts 6 phosphoglucono lactone to 6 phosphogluconate
Lactonase
Second half of PPP
Non oxidative
Reversible
Interconversion of sugars occur
Produce ribose
No key enzymes
PPP and Glycolysis overlaps with what intermediates?
Glucose 6 phosphate
Glyceraldehyde e phosphate
Fructose 6 phosphate
Cellular antioxidant
Reduces Glutathione disulfide(GSSG) to sulfhydryl form GSH
Glutathione reductase / selenium
Thiamine (Vit B1) deficiency in alcoholics
Wernickes korsakoffs
Deficient transketolase activity
Genetic deficiency of NADPH oxidase i. WBC
Lacks respiratory burst
Susceptible to catalase positive organism
Negative nitroblue tetrazolium test
Chronic granulomatous disease
Inner mitochondrial membrane (3)
ETC
Succinate Dehydrogenase
ATP synthase
Final common pathway in aerobic cells by which electrons derived from various substrates are transferred to oxygen
Electron Transport chain
Respiratory chain pathway
Oxidative phosphorylation
Synthesis of ATP from ADP by phosphorylation coupled with the exergonic breakdown of a high energy organic substrate molecule
Substrate level phosphorylation
Enzymes with substrate level phosphorylation (3)
Pyruvate kinase
Phosphoglycerate kinase
Succinylcholine CoA Synthase
Phosphorylation of ADP is coupled with the oxidation of substrate in the ETC
Oxidative phosphorylation
Final acceptor of electrons along ETC
Oxygen
Iron containing component of ETC
Cytochromes
The only mobile, water soluble protein cytochrome
Cytochrome C
A non protein isoprenoid quinone
Most abundant
Shares structural homologous with Vit E and A
Ubiquinone (Coenzyme Q)
Associated with metalloflavoproteins and cytochrome B
Fe-sulfur complex
Complexes of ETC (4 - 5)
Complex 1 - NADH dehydrogenase
Complex 2 - succinate dehydrogensase
Complex 3 - cytochrome b-c1 complex
Complex 4 - cytochrome oxidase
Complex 5 - ATP synthase
2 domains of ATP synthase (complex 5)
Fo - inhibited by OLIGOMYCIN
F1 domain
Inhibitors of complex 1 (NADH dehydrogenase)
A -Barbiturate
Amytal
R - RotenONE
P - Pericidine
These do not deplete ATP production because they do not block the complex II
Inhibitors of complex 2 (succinate dehydrogenase)
Malonate
TTFA (Thenoyl trifluroacetone)
Carboxin
You still have ATP production via complex 1
A chelating agent that blocks complex II
TTFA (Thenoyl trifluoroacetone)
Inhibitors of complex 3 (Q cytochrome c oxidoreductase)
Antomycin A
Dinercapror
No ATP Produced!
Inhibitors of complex 4 cytochrome oxidase
Cyanide
CO
Na azide
H2S
Used in treatment for arsenic, gold, mercury, peas and other toxic metals
Dimercaprol
- blocks complex III
Compounds that allow oxidation to continue without corresponding ATP synthesis
Uncouplers
Ex. Thermogenin and 2,4 dinitrophenol and aspirin
Known uncoupling protein 1 or UCP1 found in brown adipose tissues (newborns)
Used to generate heat
Thermogenin
Transports protons across the membrane and destroy the pH gradient
Uncouplers
Fat soluble vitamins
Vit A D E K
Energy yield from lipids
9kcal/gram
Energy yield from protein or carbohydrates
4 kcal/gram
Major dietary fat
Triglycerides
Saturated FA mostly comes from
Animal fats (meat, poultry, butter)
Increased incidence of coronary artery disease because of high LDL
Polyunsaturated FA (PUFA) mostly comes from
Plant Oils (corn, sesame, soybeans, tuna)
Group of fatty acid that’s good for the heart
Omega 3 Fatty acids
Fatty acid in coconut oil
LAURIC ACID C12
Saturated FA
coconut oil and soaps
Monolaurin - antimicrobial for acne and psoriasia
Treatment of hypercholesterolemia
Diets that contain MUFA and PUFA
Treatment of hypertriglyceridemia and protection from thrombosis
Omega 3 class of PUFA
Organelle in the cell that is responsible for the metabolism of very long fatty acids
Peroxysomes
Contains emzymes for B oxidation
Palmitic acid
16 carbons - Hexadecanoid acid
Firat FA produced during lipogenesis
Most common saturated FA in animals and plants
Good for the skin
Stearic acid
18 carbons = octadecanoic acid
“Stearing wheel = 18yo”
Cosmetics
Soaps
Myristic acid
14 carbons
Palm and coxonut oil
Butter
Milk
Fatty acids treatment of autism
Body can synthesize needed fat except
Linoleic and alpha linolenic acid
The only absolute Essential Fatty Acid
Linoleic Acid
Precursor of arachidonic acid
Precursot of EPA and DHA
LinoLENIC acid
Lowers TAGs and increases cholesterol clearance from plasma
LinoLEIC acid (C18)
2 double bonds
LinoLENIC acid (C18)
3 double bands
Arachidonic acid (C20)
4 double bonds
A 20 Carbon Omega 6 Fatty acid with 4 double bonds
Give rise to Eicosanoids
Arachidonic acid
Drug that inhibits thromboxane A2
Antiplatelet property
Aspirin
Leukotriene inhibitors treatment for asthma
Montelukast
Zafirlukast
Black box warning for montelukast
Depression
Hallucinations
Singulair
Hostility
Sleep disturbances
Adults: suicidal thought
Anti-inflammatory drug inhibits phospholipase A2
Steroids
COX 2 specific inhibitors
Celecoxib
Rofecoxib (vioxx - CVS effects - MI, CAD)
Parecoxib (IV)
Etoricoxib
Side effects of blocking Cox-1 activity
Gastritis
GI bleed
Used for prophylaxis for colon CA
Aspirin
Produced by endothelial cells of blood vessels
Causes vasodilation
Inhibits platelet aggregation
Increase camp
Prostacyclin (PGI2)
Produced by platelets
Promote platelet aggregation
Decrease camp
Vasoconstrict
Contractuon of smooth muscles
Thromboxane A2 (TXA2)
Produced by most tussues especially kidneys
Causes arteriolar vasodilation
Increase cap permeability
Evokes chemokinesis of T cells
Enhance PAIN caused by histamine and bradykinin
induce labor
Prostaglandin E2 (PGE 2)
PGE1 agonist used to treat peptic ulcer but the side effect is abortion
Misoprostol
PGE2 in obstetrics
Dinoprostone
Mast cell stabilizer used for tx of asthma
Cromolyn sodium
Largest amount of stored energy in the body
Triacylglycerol
Energy source reserved for strenuous muscular activity
Muscle glycogen
Primary source of carbon for maintaining blood glucose levels during an overnight fast
Liver glycogen
Major precursor of urea in urine
Protein
After a fast for a few days, ketone bodies become an important fuel
Brain
Ketone bodies are used as a fuel after an overnight fast
Skeletal muscle
Fatty acids are not a significant fuel source at any time
Red blood cell
During starvation, this tissue uses amino acids to maintain blood glucose levels
Liver
This tissue converts lactate from muscle to a fuel for other tissues
Liver
Major process for maintaining blood glucose levels after an overnight fast
Liver GLYCOGENOLYSIS
Major fuel store of the body
Adipose triacylglycerol
Non specific but considered as the standard for assessing overall protein malnutrition
Albumin
Bond formed when a carboxylic acid reacts with phosphoric acid releasing H2O
Anhydride bond
Bond formed when phosphoric acid reacts with an alcohol releasing water
Phosphate ester
Bond formed when a phosphate group contains two ester linkages as in structures of the nucleic acids
Phosphodiester
This phase of cell cycle, the cells prepare to duplicate their chromosomes
G1
This phase of cell cycle is where the synthesis of DNA (replication) occurs
S phase
This phase of cell cycle where the cell prepares to divide
G2
This phase of the cell cycle is where the cell division occurs
M phase
Clustering of receptors over clathrin-coated pits in the inner membrane and then invagination of the membrane to form an intracellular vesicle that contains the receptor-growth factor complex
Receptor mediated endocytosis
Endocytosis without the receptors – vesicle formation
Pinocytosis
Receptor mediated entry into a cell through caveolae
Potocytosis
Formation of membrane around a particle and then the endocytosis of that membrane containing the particle
Phagocytosis
Results from the inability to appropriately target lysosomal proteins and it is a lysosomal storage disease
I cell disease
Chief inhibitory neurotransmitter
GABA
Contains the most triacylglycerol
Least dense of the blood lipoproteins
Chylomicrons
Contains more protein than chylomicron
Demser than Chylomicrons but less dense than LDL
VLDL
Produced by the degradation of the triacylglycerols of VLDL
LDL
Most dense of the blood lipoproteins
Has the most protein and least triacylglycerol
HDL
Determining factor if a Beta oxidation will occur
Chain length
<10-12 carbons = no need for carnitine
Strong indicator of fatty acid oxidation problem
Hypokinetic hypoglycemia
Neuro deficit
Lactic acidosis
Increase serum alanine starting infancy
Build up of pyruvate that gets shunted to lactate and alanine
Dx?
Tx?
Pyruvate dehydrogenase complex deficiency
Tx: ketogenic diet
Pentose phosphate pathway
HMP shunt
Aldolase B deficiency
Hypoglycemia
Jaundice
Cirrhosis
Vomiting
—- after eating fruit, juice or honey
Dx?
Hereditary fructose intolerance
Glucogenic amino acids
Methionine
Histidine
Valine
“Met His Val-entine”
Most common urea cycle disorder
Interferes with body’s ability to eliminate ammonia
Increase orotic acid blood and urine
Decrease BUN
Ornithine transcarbamylasr deficiency
pH at which an equivalent distribution of acid and conjugate base exist in solution
PKa
pH at which the molecule is electrically neutral
Isoelectric point
A solution or substance which resists changes in pH when small quantities of an acid or base are added to it
Buffering
More likely to be exposed to water than to be found in the interior of a folded protein
Polar amino acids
The greatest buffering capacity at physiological pH would be provided by a protein rich in which amino acid?
Histidine
Hallmark feature of Gaucher disease
Presence of lipid-engorged cells of the monocyte/macrophage lineage with a characteristic appearance in variety of tissues
Disease where ganglioside GM2 is NOT catabolized
Tay sachs disease
Absent hexosaminidase A
The carbon about which the rotation occurs in ring structures of carbohydrates is the?
Anomeric carbon
2 forms = anomers
Deficiency of hepatic enzyme ALDOLASE B would result in a reduced ability to metabolize which carbohydrates?
Fructose
Backbone of glycosphingolilids
Ceramide
Globotriaosylceramide
Disorder characterized by lysosomal accumulation of glycosphingolipud with terminal a-galactosyl residues
Fabry disease
Class of lipid involved in the resolution of inflammatory responses
Resolvins
Class D - DHA
Class E - EPA
In patient with Severe Combined Immunodeficiency (SCID), what compound is expected to be elevated in the blood?
Adenosine and DEOXYADENOSINE
Adenosine deaminase deficiency (ADA)
In patient with Lesch-Nyhan syndrome, what compound is expected to be elevated in the urine?
In serum?
Urine — Uric acid
Serum — xanthine
Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
Protein structure resulting from interaction at least 2 protein subunits in the functional protein
Quaternary structure
