1
Q
When does amino acid catabolism occur?
A
During fasting, low carbohydrate intake, prolonged exercise, illness, or excess dietary protein when amino acids are used for energy or gluconeogenesis.
2
Q
What is the first step in amino acid catabolism for most amino acids?
A
Transamination: transfer of the amino group to an α-keto acid (usually α-ketoglutarate), catalyzed by aminotransferases (transaminases) using PLP as coenzyme.
3
Q
What enzyme class catalyzes transamination reactions?
A
Aminotransferases (transaminases), which are PLP-dependent enzymes.
4
Q
What is the typical amino acceptor in transamination?
A
α-Ketoglutarate, which accepts amino groups to form glutamate.
5
Q
What is oxidative deamination and which enzyme catalyzes it in the liver?
A
Oxidative deamination converts glutamate to α-ketoglutarate and free NH4+; catalyzed by glutamate dehydrogenase (GDH) in mitochondria.
6
Q
What happens to the amino group after transamination and oxidative deamination?
A
The amino group becomes free ammonia (NH4+), which is converted to urea in the urea cycle (in liver) or handled via other pathways.
7
Q
What are the carbon skeletons of amino acids used for?
A
become TCA cycle intermediates:
pyruvate
acetyl-CoA
or ketone bodies for energy production or gluconeogenesis.
8
Q
Which coenzyme is essential for transaminase activity?
A
Pyridoxal phosphate (PLP), the active form of vitamin B6.
9
Q
Describe the ping-pong mechanism of transaminases.
A
The enzyme takes an amino group from the first amino acid, forms a PLP-Schiff base, and releases a keto acid. Then it transfers that amino group to a second keto acid. The enzyme never holds all substrates at once (no ternary complex).
10
Q
How are transaminases used diagnostically for liver damage?
A
ALT (alanine aminotransferase) and AST (aspartate aminotransferase) are released into blood when hepatocytes are damaged; elevated levels indicate liver injury.
11
Q
What is transdeamination?
A
A two-step process: transamination of an amino acid to form glutamate, followed by oxidative deamination of glutamate to release NH4+; occurs mainly in liver.
12
Q
Where does ammonia produced in the body primarily come from?
A
Amino acid breakdown, intestinal bacterial metabolism, purine/pyrimidine catabolism, and amino acid deamination in tissues.
13
Q
Why is ammonia toxic to the brain?
A
High NH4+ disrupts neurotransmitter balance, causes astrocyte swelling via glutamine accumulation, leads to cerebral edema, altered energy metabolism, and encephalopathy.
14
Q
What clinical signs suggest hepatic encephalopathy from ammonia toxicity?
A
Confusion, asterixis (flapping tremor), decreased consciousness, and in severe cases coma.
15
Q
Name clinical remedies to reduce blood ammonia in liver failure.
A
Lactulose (acidifies colon, traps ammonia as NH4+)
rifaximin
nonabsorbable antibiotics (reduce ammonia-producing bacteria)
dietary protein adjustment
hemodialysis in severe cases.
16
Q
Explain the glucose–alanine cycle.
A
- in muscle pyruvate from glycolysis accepts amino groups (from glutamate) to form alanine
2.alanine travels to the liver;
3.there alanine is converted back to pyruvate (used for glucose via gluconeogenesis)
4.the nitrogen enters the urea cycle for disposal, supplying muscles with needed glucose
17
Q
What is the physiological implication of the glucose–alanine cycle?
A
Shuttles nitrogen from muscle to liver, provides substrate for hepatic gluconeogenesis during fasting or exercise, helps detoxify muscle-derived NH4+.
18
Q
List the main steps of the urea cycle in order.
A
1) Carbamoyl phosphate synthase I (CPS1) forms carbamoyl phosphate;
2) Ornithine transcarbamylase (OTC) forms citrulline;
3) Citrulline + Asp → argininosuccinate (ASS);
4) Argininosuccinate → arginine + fumarate (ASL);
5) Arginase converts arginine → urea + ornithine.
19
Q
Where does the urea cycle occur in the cell?
A
Partially in mitochondria (CPS1 and OTC) and partially in the cytosol (ASS, ASL, arginase) of hepatocytes.
20
Q
What are the sources of the two nitrogen atoms in urea?
A
One nitrogen from free ammonia (NH4+), the second nitrogen from aspartate.
21
Q
What is the carbon source of urea?
A
Bicarbonate (HCO3−), which is used to form carbamoyl phosphate.
22
Q
What is the energetic cost of the urea cycle per urea produced?
A
Consumes 4 high-energy phosphate bonds:
3 ATP equivalents (CPS1 uses 2 ATP to make carbamoyl phosphate—one becomes AMP—so counted as 2 ATP equivalents; ASS uses 1 ATP)
total equivalent to 4 ATP hydrolyses when accounting AMP → 2Pi.
23
Q
How is the urea cycle regulated allosterically?
A
N-acetylglutamate (NAG) is an essential allosteric activator of CPS1; its synthesis is stimulated by arginine.
24
Q
How is the urea cycle connected to the TCA cycle?
A
Argininosuccinate cleavage yields fumarate which can be converted to malate and enter the TCA cycle or gluconeogenesis; also aspartate links to oxaloacetate.
25
Which amino acids are essential in humans? (Mnemonic PVT TIM HALL)
Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine* (conditionally essential in children), Leucine, Lysine.
26
Which amino acids are purely ketogenic?
Leucine and Lysine are purely ketogenic.
27
Which amino acids are both ketogenic and glucogenic?
Isoleucine, Phenylalanine, Tyrosine, Tryptophan, and Threonine (depending on pathway) — commonly Ile, Phe, Tyr, Trp are mixed.
28
Name common coenzymes involved in amino acid catabolism.
Pyridoxal phosphate (PLP, B6),
NAD+/NADP+
FAD
tetrahydrofolate (THF)
S-adenosylmethionine (SAM)
biotin
lipoic acid
cobalamin (B12).
29
What diseases are associated with PLP deficiency?
Neuropathy, sideroblastic anemia, impaired amino acid metabolism, and seizures in severe deficiency.
30
Which drugs can interfere with vitamin B6 (PLP) metabolism?
Isoniazid (can cause B6 deficiency)
penicillamine
hydralazine
31
What is Phenylketonuria (PKU)?
A genetic deficiency of phenylalanine hydroxylase (PAH) or BH4 cofactor leading to accumulation of phenylalanine and phenylpyruvate causing intellectual disability if untreated.
32
How is PKU managed clinically?
Dietary restriction of phenylalanine, supplementation with tyrosine (conditionally essential), BH4 (sapropterin) in BH4-responsive patients.
33
What is Maple Syrup Urine Disease (MSUD)?
Defect in branched-chain α-ketoacid dehydrogenase complex causing buildup of branched-chain amino acids (Leu, Ile, Val) and their ketoacids; causes neurological damage and sweet-smelling urine.
34
How is MSUD managed?
Dietary restriction of branched-chain amino acids, thiamine supplementation if responsive, and emergency management to reduce catabolism.
35
What is Ornithine Transcarbamylase (OTC) deficiency?
An X-linked urea cycle disorder causing hyperammonemia due to inability to incorporate carbamoyl phosphate into citrulline; leads to elevated orotic acid.
36
How do you treat hyperammonemia from urea cycle defects?
Protein restriction, nitrogen scavenger drugs (sodium benzoate, sodium phenylbutyrate), arginine/citrulline supplementation as appropriate, dialysis in severe cases.
37
What is hyperhomocysteinemia and what are its consequences?
having elevated levels of the amino acid homocysteine in your blood, often due to B vitamin deficiencies (folate, B6, B12) or genetic factors
risk factor for serious conditions like heart attack, stroke, blood clots (thrombosis), and potentially cognitive decline by damaging blood vessel linings and promoting plaque buildup
38
Which vitamins are involved in one-carbon and amino acid metabolism?
Folate (B9), cobalamin (B12), and pyridoxine (B6) are key for one-carbon transfers, methionine/homocysteine metabolism, and transamination.
39
Which antibiotics inhibit folate synthesis and affect nucleotide metabolism?
Sulfonamides (e.g., sulfamethoxazole) inhibit dihydropteroate synthase; trimethoprim inhibits dihydrofolate reductase; combo is bactericidal (Bactrim).
40
What is methylmalonic acidemia?
An inborn error in methylmalonyl-CoA mutase or cobalamin metabolism leading to accumulation of methylmalonic acid, metabolic acidosis, and developmental issues.
41
Which cofactor is required by methylmalonyl-CoA mutase?
Adenosylcobalamin (a form of vitamin B12).
42
How does kidney failure affect amino acid and nitrogen metabolism?
Reduced renal urea excretion increases BUN; impaired ammoniagenesis and acid-base disturbances; altered amino acid handling.
43
Define azotemia and its indicator.
Azotemia is elevated blood urea nitrogen (BUN) and creatinine indicating reduced renal function or increased nitrogen generation.
44
What is asterixis and which condition is it associated with?
A flapping tremor indicative of metabolic encephalopathy, seen in hepatic encephalopathy and uremia.
45
What is the role of cellular respiration in ATP synthesis?
Cellular respiration oxidizes fuels (glucose, fatty acids) to generate reducing equivalents (NADH, FADH2) that feed the electron transport chain to create a proton gradient used to synthesize ATP.
46
State the chemiosmotic theory in brief.
cells generate ATP by using the energy from a proton (H+) gradient across a membrane ( inner mitochondrial membrane) to power ATP synthase, which phosphorylates ADP into ATP
47
Where in mitochondria do the complexes of oxidative phosphorylation reside?
The protein complexes (I-IV) of the electron transport chain and ATP synthase (Complex V) for oxidative phosphorylation are located within the inner mitochondrial membrane
48
Name the main electron carriers in oxidative phosphorylation.
NADH, FADH2, ubiquinone (coenzyme Q), cytochrome c, and iron-sulfur centers and heme groups in complexes.
49
What is Complex I and its role?
oxidizes NADH → transfers electrons to ubiquinone → pumps 4 H⁺ → helps generate ATP.
50
What is Complex II and its role?
Succinate dehydrogenase (part of TCA and ETC); oxidizes succinate to fumarate, transfers electrons to ubiquinone but does NOT pump protons.
51
What is Complex III and its role?
Name: Cytochrome bc₁ complex
What it does:
Accepts electrons from CoQH₂ (ubiquinol)
Passes them to Cytochrome c
Pumps 4 H⁺
52
What is Complex IV and its role?
Cytochrome c oxidase; transfers electrons from cytochrome c to O2 forming water and pumps protons to contribute to the gradient.
53
What is Complex V?
ATP synthase: uses proton flow from intermembrane space back to matrix to synthesize ATP from ADP and Pi.
54
How is the proton motive force (PMF) composed?
PMF = electrical potential (membrane potential, Δψ) + chemical gradient (ΔpH). Protons pumped into intermembrane space create both components.
55
How many protons approximately are required to synthesize one ATP?
Roughly 3 protons through ATP synthase per ATP (plus ~1 proton for phosphate transport) — overall ~4 H+ per ATP synthesized depending on rotor stoichiometry.
56
Name common inhibitors of electron flow and their targets.
Rotenone (Complex I)
antimycin A (Complex III)
cyanide/azide/carbon monoxide (bind Complex IV)
malonate (Complex II competitive inhibitor).
57
Name inhibitors of ATP synthase.
Oligomycin inhibits ATP synthase by blocking the proton channel (Fo subunit).
58
What are uncouplers and give examples?
substances or proteins that disrupt the link between the electron transport chain (ETC) and ATP synthesis in mitochondria, allowing protons to leak back into the matrix, bypassing ATP synthase
2,4-dinitrophenol (DNP)
FCCP
thermogenin (UCP1) in brown adipose tissue.
59
How can electron flow be uncoupled physiologically?
Via uncoupling proteins (UCPs) in mitochondria which allow protons to re-enter matrix generating heat instead of ATP.
60
How is oxidative phosphorylation regulated?
By substrate availability (ADP, Pi, O2), NADH/NAD+ ratio, proton gradient, and via allosteric regulation and mitochondrial biogenesis signals.
61
How do reactive oxygen species (ROS) arise from mitochondria?
from the electron transport chain (ETC), especially complexes I and III, where electrons "leak" prematurely to oxygen, creating superoxide (O dot) instead of fully forming water
62
What is the role of mitochondria in apoptosis?
Release of cytochrome c and other pro-apoptotic factors from intermembrane space activates caspase cascade; mitochondrial outer membrane permeabilization is key.
63
Describe mitochondrial genetics particularities.
Mitochondrial DNA is maternally inherited, circular, present in multiple copies, encodes some ETC proteins and tRNAs; heteroplasmy can affect disease severity.
64
Where does fatty acid biosynthesis occur in eukaryotic cells?
In the cytosol (primarily in liver and adipose tissue);
65
What is the committed step of fatty acid synthesis?
Formation of malonyl-CoA from acetyl-CoA catalyzed by acetyl-CoA carboxylase (ACC), using biotin and ATP.
66
What enzyme carries out fatty acid synthase (FAS) activity in animals?
multifunctional enzyme complex (Type I FAS), encoded
67
What is the role of ACP (acyl carrier protein)?
ACP carries the growing acyl chain via a phosphopantetheine prosthetic group, presenting substrates to FAS active sites.
68
What reducing power is required for fatty acid synthesis?
NADPH is the reducing agent, provided mainly by the pentose phosphate pathway and malic enzyme.
69
How is cytosolic acetyl-CoA generated for fatty acid synthesis?
mitochondrial acetyl-CoA, transported as citrate via the citrate shuttle system
70
How is acetyl-CoA carboxylase regulated?
Activated by:
citrate (allosteric)
dephosphorylation (insulin signaling);
inhibited by:
palmitoyl-CoA (feedback)
phosphorylation by AMPK (glucagon/epinephrine signaling).
71
How are unsaturated fatty acids synthesized in humans?
through the action of desaturase enzymes, which introduce double bonds into existing saturated fatty acid chains (like palmitate), using oxygen and NADPH
72
What are essential fatty acids?
Linoleic acid (omega-6) and alpha-linolenic acid (omega-3); precursors to longer PUFAs like arachidonic acid, EPA, and DHA.
73
What is the key precursor for triacylglycerol (TAG) synthesis?
Glycerol-3-phosphate is the backbone; fatty acyl-CoAs are esterified to form phosphatidic acid → DAG → TAG.
74
Name the rate-limiting enzyme of cholesterol biosynthesis.
HMG-CoA reductase (converts HMG-CoA to mevalonate); major regulatory target of statins.
75
What drugs inhibit HMG-CoA reductase?
Statins (e.g., lovastatin, rosuvastatin) are competitive inhibitors that reduce cholesterol synthesis.
76
How is cholesterol transported in blood?
lipoproteins, which act like blood-compatible carriers, moving it to cells.
Low-Density Lipoproteins (LDL), which deliver cholesterol to tissues (often called "bad" cholesterol)
High-Density Lipoproteins (HDL), which collect excess cholesterol and return it to the liver for removal (the "good" cholesterol).
77
What is the role of LDL and HDL in atherosclerosis risk?
Elevated LDL contributes to plaque formation (atherosclerosis); HDL is protective by promoting reverse cholesterol transport to the liver.
78
Name cholesterol-lowering and lipid-modifying drugs.
Statins, bile acid sequestrants (cholestyramine), fibrates (fenofibrate), niacin (vitamin B3), omega-3 fatty acid supplements (EPA/DHA).
79
Which steroid hormones derive from cholesterol?
Progesterone, cortisol, aldosterone, testosterone, estradiol, and other sex and adrenal hormones are synthesized from cholesterol.
80
What disease is associated with defective cholesterol handling leading to atherosclerosis?
Hypercholesterolemia leading to atherosclerosis and coronary heart disease.
81
What is the major reaction class for amino acid biosynthesis?
The major reaction class for amino acid biosynthesis is transamination
82
What is the primary source of ammonia for amino acid biosynthesis?
Glutamate acts as the primary amino donor; glutamine also donates amino groups via amidotransferases.
83
Which metabolic precursors give rise to amino acids? Give examples.
TCA intermediates (oxaloacetate → Asp → Asn; α-ketoglutarate → Glu → Gln); glycolysis intermediates (3-phosphoglycerate → Ser); pyruvate → Ala, Val, Leu; erythrose-4-phosphate & phosphoenolpyruvate → aromatic AAs via shikimate (in microbes/plants).
84
How is DOPA synthesized and what is it a precursor for?
Tyrosine is hydroxylated by tyrosine hydroxylase to DOPA, which is decarboxylated to dopamine; dopamine is precursor to norepinephrine and epinephrine.
85
How is GABA synthesized?
Glutamate is decarboxylated by glutamate decarboxylase (PLP-dependent) to form GABA.
86
How are serotonin and histamine synthesized?
Serotonin: tryptophan → 5-hydroxytryptophan (via tryptophan hydroxylase) → decarboxylation to serotonin. Histamine: histidine decarboxylated by histidine decarboxylase (PLP-dependent).
87
What is the porphyrin synthesis starting material?
Glycine + succinyl-CoA condense to form δ-aminolevulinic acid (ALA) via ALA synthase (requires PLP).
88
Where is heme synthesized and what are key intermediates?
In mitochondria and cytosol (steps alternate): ALA → porphobilinogen → hydroxymethylbilane → uroporphyrinogen → coproporphyrinogen → protoporphyrin → heme (insertion of Fe2+ by ferrochelatase).
89
Name a disease of heme biosynthesis and a key sign.
Porphyrias (e.g., acute intermittent porphyria) — symptoms include abdominal pain, neuropathy, photosensitivity (depending on type), and dark urine.
90
How is heme catabolized and what pigments are produced?
Heme → biliverdin (via heme oxygenase, releases CO) → bilirubin (via biliverdin reductase); bilirubin is conjugated in liver and excreted in bile.
91
What causes neonatal jaundice and how is it treated?
Immature UDP-glucuronosyltransferase leads to increased unconjugated bilirubin; treated with phototherapy (converts bilirubin to water-soluble isomers) or exchange transfusion if severe.
92
What is the difference between conjugated and unconjugated hyperbilirubinemia?
Unconjugated (indirect): pre-hepatic (hemolysis) or impaired conjugation; conjugated (direct): cholestasis or hepatocellular damage preventing excretion.
93
What are the building blocks/sources of atoms in purine rings?
Purine atoms derive from: glycine, formyl-THF (2 atoms), glutamine (amide N), aspartate (N), and CO2 (bicarbonate) — built on ribose-5-phosphate (PRPP).
94
What is the first committed step in purine biosynthesis?
PRPP amidotransferase converts PRPP + glutamine → 5-phosphoribosylamine, regulated by feedback inhibition by IMP, AMP, GMP.
95
Which drugs inhibit purine or pyrimidine synthesis?
6-mercaptopurine (inhibits steps in purine synthesis), allopurinol (xanthine oxidase inhibitor for uric acid), 5-fluorouracil (inhibits thymidylate synthase), methotrexate (inhibits dihydrofolate reductase).
96
What is the source of atoms in pyrimidine rings?
Pyrimidine ring atoms come from aspartate, carbamoyl phosphate (from bicarbonate + ammonium), and PRPP provides ribose (ring synthesized then attached to PRPP).
97
How is uric acid formed and what disease results from its accumulation?
Purine degradation yields xanthine → uric acid (via xanthine oxidase); accumulation causes gout.
98
How is gout treated pharmacologically?
Allopurinol (xanthine oxidase inhibitor), febuxostat (non-purine xanthine oxidase inhibitor), uricase (pegloticase) for refractory cases; NSAIDs and colchicine for acute flares.
99
What are the main classes of mammalian hormones by chemical nature?
Peptide/protein hormones, steroid hormones (cholesterol-derived), amino-acid derived (catecholamines, thyroid hormones), and eicosanoids (lipid-derived).
100
What receptor types do peptide hormones usually bind?
Cell-surface receptors (GPCRs or receptor tyrosine kinases) because peptides are not membrane-permeable.
101
What receptor type do steroid hormones bind?
Intracellular (cytoplasmic or nuclear) receptors that act as transcription factors when ligand-bound.
102
What is the structure of insulin and how is it processed?
Insulin is synthesized as preproinsulin → proinsulin (disulfide bonds form) → cleavage yields mature insulin (A and B chains linked by disulfide bonds) + C-peptide.
103
Name types of therapeutic insulin and a difference among them.
Rapid-acting analogs (lispro, aspart) have altered amino acids for faster absorption; long-acting analogs (glargine, detemir) provide prolonged basal insulin.
104
How does the well-fed state affect metabolism? (hormones & processes)
Insulin predominates: promotes glucose uptake, glycogen synthesis, fatty acid synthesis, and protein synthesis; inhibits gluconeogenesis and lipolysis.
105
What metabolic changes occur during fasting?
Glucagon and epinephrine dominate: glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis (if prolonged).
106
What are caloric values of macronutrients per gram?
Carbohydrates ~4 kcal/g, Proteins ~4 kcal/g, Fats ~9 kcal/g, Alcohol ~7 kcal/g.
107
What are features of type 1 vs type 2 diabetes?
Type 1: autoimmune β-cell destruction → absolute insulin deficiency; Type 2: insulin resistance with relative insulin deficiency; Type 2 associated with obesity and metabolic syndrome.
108
Name some newer antidiabetic drug classes.
GLP-1 receptor agonists (e.g., semaglutide), DPP-IV inhibitors (e.g., sitagliptin), SGLT2 inhibitors (e.g., canagliflozin), insulin analogs, and amylin analogs (pramlintide).
109
What is the biological value of a protein?
Measure of how efficiently the body uses dietary protein to synthesize tissue protein; depends on amino acid composition and digestibility.
110
What is pellagra and its cause?
Niacin (B3) deficiency causing dermatitis, diarrhea, dementia (the three Ds); can be caused by diets low in tryptophan or niacin.
111
What causes beri-beri and what vitamin is involved?
Thiamine (B1) deficiency causing beriberi: neurological (dry) and cardiac (wet) forms.
112
What is pernicious anemia?
Autoimmune destruction of gastric parietal cells or intrinsic factor deficiency leads to B12 deficiency and megaloblastic anemia.
113
Where is DNA located in eukaryotic cells?
Primarily in the nucleus (linear chromosomes) and also in mitochondria (circular mitochondrial DNA).
114
What is DNA supercoiling and why is it important?
Over- or under-winding of DNA helix; affects replication/transcription; topoisomerases modulate supercoiling to allow strand separation.
115
What enzymes relax or introduce supercoils?
Topoisomerase I (cuts one strand, relaxes supercoils), Topoisomerase II (cuts both strands, can introduce negative supercoils) and gyrase in bacteria.
116
Which drugs target topoisomerases?
Quinolones (nalidixic acid, ciprofloxacin) target bacterial gyrase/topo IV; camptothecin/topotecan/irinotecan target eukaryotic topo I; doxorubicin/etoposide target eukaryotic topo II.
117
What are the main types of RNA and their functions?
mRNA (carries coding info), tRNA (delivers amino acids), rRNA (ribosome structure/function), plus snRNA, miRNA, siRNA for regulation/processing.
118
Describe the basic steps of transcription in eukaryotes.
Initiation (RNA Pol II and transcription factors assemble at promoter), elongation (RNA synthesis), RNA processing (5' capping, splicing, 3' polyadenylation).
119
What is the genetic code start codon and what amino acid does it code for in eukaryotes?
Start codon AUG codes for methionine (Met); in prokaryotes formylmethionine (fMet) is used.
120
Name major antibiotics/toxins that inhibit translation and their targets.
Tetracyclines (block tRNA binding to A site), aminoglycosides (cause misreading), chloramphenicol (inhibit peptidyl transferase in bacteria), puromycin (premature chain termination), diphtheria toxin (inhibits eukaryotic EF-2).
121
What is mRNA processing in eukaryotes?
5' capping, splicing to remove introns, and 3' polyadenylation; processed mRNA exported to cytoplasm for translation.
122
What is the role of ribosomes in translation?
Ribosomes catalyze peptide bond formation, read mRNA codons, and coordinate tRNA entry at A site, peptidyl transfer at P site, and exit at E site.
123
What lab tests assess liver injury and which enzymes are measured?
ALT (alanine aminotransferase, GPT) and AST (aspartate aminotransferase, GOT) — AST also found in muscle; ALT is more liver-specific.
124
What is BUN and what does it indicate?
Blood Urea Nitrogen (BUN) reflects urea concentration in blood — elevated in renal failure, dehydration, or high protein catabolism.
125
What is the mechanism of action of lactulose in hepatic encephalopathy?
Nonabsorbable disaccharide metabolized by gut bacteria to acids, acidifies colon converting NH3 to NH4+ (trapped), reduces ammonia absorption.
126
What is Sapropterin (Kuvan®) used for?
A synthetic BH4 cofactor used in some BH4-responsive PKU patients to enhance residual phenylalanine hydroxylase activity.
127
What is the target of methotrexate and why does it affect nucleotide synthesis?
Methotrexate inhibits dihydrofolate reductase (DHFR), reducing THF availability for thymidylate and purine synthesis, impairing DNA synthesis.
128
How does allopurinol treat gout?
Allopurinol is a xanthine oxidase inhibitor that reduces uric acid production and increases xanthine/hypoxanthine, which are more soluble.
129
What is the action of febuxostat?
A non-purine xanthine oxidase inhibitor used to lower uric acid in gout patients.
130
What are statins' main pleiotropic effects beyond lowering LDL?
Improve endothelial function, stabilize atherosclerotic plaques, reduce inflammation, and have antithrombotic effects.
131
How should you use active recall for these flashcards?
Try to answer the question before flipping the card, speak the answer out loud, and check for gaps; use spaced repetition intervals and error-targeted review.
132
What is spaced repetition and why is it effective?
Spaced repetition reviews material at increasing intervals to exploit the spacing effect and counteract forgetting, strengthening long-term retention.
133
How can you make difficult cards easier to remember?
Break into smaller steps, use mnemonics (e.g., PVT TIM HALL), draw pathways, and create clinical vignettes to contextualize facts.
134
Catabolism of FA produces
Acetyl-CoA
135
Where does catabolism of FA occur?
Mitochondria
136
Anabolism of fatty acids requires
Acetyl-CoA
137
Where does anabolism of FA occur?
Cytosol
138
Fatty acids process ___ acetate at a time
1
139
What hormone activates fatty acid synthesis?
Insulin
140
How does insulin activate FA synthesis?
Activates ACC → converts acetyl-CoA → malonyl-CoA
141
What hormone inhibits FA synthesis?
Glucagon and epinephrine
142
ACC is inhibited by
Palmitoyl-CoA
143
ACC is activated by
Citrate
144
How many steps elongate FA by 2 carbons?
4
145
Fatty acid synthase complex
All enzymes + binding proteins needed for FA synthesis
146
Steps of FA synthesis
Condensation → Reduction → Dehydration → Reduction
147
Acyl carrier protein (ACP)
Carries acetate/malonate to FA synthase
148
4'-phosphopantetheine
Flexible arm that carries intermediates between enzymes
149
Reaction to make 7 malonyl-CoA
7 Acetyl-CoA + 7 CO₂ + 7 ATP → 7 malonyl-CoA + 7 ADP + 7 Pi
150
Reaction to make palmitate
1 Acetyl-CoA + 7 malonyl-CoA + 14 NADPH → Palmitate + CO₂ + CoA + NADP⁺ + H₂O
151
Sources of NADPH for FA synthesis
Malate → pyruvate & Pentose phosphate pathway
152
Where is acetyl-CoA made?
Mitochondria
153
How is acetyl-CoA transported to cytosol?
Converted to citrate → transported → citrate lyase releases acetyl-CoA
154
Where does most FA synthesis occur?
Liver
155
Ratio of ω-6 : ω-3 importance
Too high → cardiovascular disease risk
156
Backbone synthesis for TAG/phospholipids
DHAP → glycerol-3-P (GPDH) or glycerol kinase
157
Phosphatidic acid
Common precursor for TAGs & phospholipids
158
ATP needed to make phosphatidic acid from glycerol-3-P
2 ATP
159
Phosphatidic acid becomes
TAGs or phospholipids
160
Phosphatidic acid phosphatase
Converts phosphatidate → DAG → TAG
161
Insulin increases
Conversion of carbs & proteins → fats
162
Triacylglycerol cycle
Balances liver TAG use vs adipose TAG storage
163
Glyceroneogenesis
Makes glycerol-3-P for TAG synthesis when glycolysis low
164
DHAP dehydrogenase role
Makes glycerol-3-P for glyceroneogenesis
165
When glycolysis inhibited
DHAP must be made via glyceroneogenesis
166
Thiazolidinediones
Increase insulin sensitivity; activate PPARs
167
Rosiglitazone (Avandia)
Thiazolidinedione
168
Pioglitazone (Actos)
Thiazolidinedione
169
Insulin resistance
Cells fail to respond to insulin; associated with high FFAs; link to type 2 diabetes
170
Intermediates of cholesterol synthesis
Acetate → Mevalonate → Activated isoprene → Squalene → Cholesterol
171
How is mevalonate formed?
Acetyl-CoA → acetoacetyl-CoA → HMG-CoA → mevalonate (HMG-CoA reductase)
172
What do statins target?
HMG-CoA reductase
173
How do statins work?
Lower mevalonate → lower cholesterol
174
Where is cholesterol synthesized?
Liver
175
Cholesterol exported as
Bile acids; biliary cholesterol; cholesteryl esters
176
Where is bile stored?
Gallbladder
177
Taurocholic acid is a bile acid?
Yes
178
Function of taurocholic acid
Emulsifies fats
179
Cholesterol converted to
steroid hormones
180
What is a cholesterol ester?
Cholesterol + fatty acid
181
Four classes of lipoproteins
Chylomicrons; VLDL; LDL; HDL
182
Lipoprotein size (largest→smallest)
Chylomicron > VLDL > LDL > HDL
183
Lipoprotein density (highest→lowest)
HDL > LDL > VLDL > Chylomicron
184
Where are chylomicrons formed?
Intestine
185
Where are VLDLs synthesized?
Liver
186
Where are LDLs produced?
Liver/blood
187
Where are HDLs synthesized?
Liver
188
"Bad" lipoproteins
LDL
189
Which lipoprotein picks up cholesterol from tissues?
HDL
190
Which lipoprotein has most cholesterol?
LDL
191
Which lipoprotein has most TAGs?
Chylomicrons
192
Atherosclerosis
Hardening of arteries from lipid plaques
193
LDL delivers cholesterol to
Tissues
194
HDL delivers cholesterol to
Liver
195
LDL uptake process
Receptor-mediated endocytosis
196
Is low HDL good or bad?
Good
197
Is high LDL good or bad?
Bad
198
Omacor
Omega-3 FA combo (EPA/DHA) → ↑ LDL receptors; ↓ VLDL synthesis
199
Hypolipidemic agents
Resins; statins; fenofibrate; niacin
200
What regulates cholesterol metabolism?
Insulin and glucagon
201
What naturally inhibits mevalonate formation?
Glucagon
202
What naturally activates mevalonate formation?
Insulin
203
Progesterone
Precursor to cortisol
204
What is the role of cellular respiration?
converts chemical energy in glucose to chemical energy in the form of ATP
205
What is the chemiosmotic theory?
the concept that a proton concentration gradient serves as the energy reservoir that drives ATP formation
206
Where does oxidative phosphorylation occur?
inner mitochondrial membrane
207
Where is there a high concentration of H+ ions?
intermembrane space
208
What occurs in the matrix of the mitochondria?
citric acid cycle
209
What is the energy source for oxidative phosphorylation?
NADH + FADH2
210
Is ATP production energetically favorable?
No
211
What does the energy made in the electron transport chain do?
Transports proton ions against an electrochemical gradient
212
Is the pH of the intermembrane space low or high?
Low because of all the H+ ions
213
As electrons move through the ETC do components become more or less prone to being reduced?
more prone to being reduced (more electronegative/positive reduction potential) because electrons flow spontaneously down an energy gradient from carriers with lower (more negative) potentials to those with higher (more positive) potentials, ultimately reaching oxygen, the final electron acceptor.
214
Pellagra is a deficiency of?
Niacin (B3)
215
Ariboflavinosis is a deficiency of?
Riboflavin (B2)
216
What is coenzyme Q?
a mobile electron carrier transporting electrons from Complexes I and II to Complex III
217
Is ubiquinone lipid soluble?
Yes
218
What type of molecule is ubiquinone?
Isoprenoid
219
What happens to ubiquinone when it picks up 2 electrons?
It picks up 2 H+ → becomes ubiquinol
220
Cytochromes?
Iron-containing proteins that are single-electron carriers in the ETC
221
What color are cytochromes when oxidized?
blue
222
What color are cytochromes when reduced?
red
223
Why are cytochromes visible?
Conjugation
224
Iron-sulfur proteins?
Proteins with iron coordinated by cysteine residues (carry 1 electron)
225
Electron transport Complex I?
NADH dehydrogenase → transfers electrons to ubiquinone; pumps 4 H+
226
Prosthetic groups of Complex I?
FMN
227
Complex II?
Succinate dehydrogenase
228
Prosthetic groups of Complex II?
FAD
229
Complex III?
Ubiquinone:cytochrome c oxidoreductase
230
Prosthetic groups of Complex III?
Heme
231
Complex IV?
Cytochrome oxidase
232
Prosthetic groups of Complex IV?
CuA
233
How much kJ from NADH?
220 kJ
234
How much kJ to make 1 ATP?
30 kJ
235
How many ATP per NADH?
3
236
Why only 3 ATP from NADH?
Excess energy lost as heat
237
How did biochemists learn ETC function?
By blocking transport at different stages
238
Rotenone and Amytal inhibit?
Complex I
239
Antimycin A inhibits?
Complex III
240
CN– and CO inhibit?
Complex IV
241
DNP?
Destroys proton gradient (uncoupler)
242
What accepts 2 electrons in Complex I?
FMN
243
How many electrons can Fe-S carry?
1
244
Which ETC complex has highest reduction potential?
Complex IV
245
Which complexes pump protons?
I
246
Largest ETC complex?
Complex I
247
Mass of Complex III?
250 kDa
248
Mass of Complex II?
140 kDa
249
Mass of Complex IV?
204 kDa
250
Mass of cytochrome c?
13 kDa
251
Subunits in Complex I?
45
252
Subunits in Complex II?
4
253
Subunits in Complex III?
11
254
Subunits in Complex IV?
13
255
How many protons does Complex I pump?
4
256
Where does NADH bind Complex I?
Matrix side
257
What donates electrons to Complex II?
FADH2
258
Where does FAD receive electrons from?
Succinate
259
Where are electrons passed in Complex II?
Ubiquinone
260
Where are electrons passed in Complex I?
Ubiquinone
261
Which TCA enzyme is Complex II?
Succinate dehydrogenase
262
Complex III function?
Uses QH2 electrons to reduce 2 cytochrome c molecules
263
How many protons moved by Complex III?
4
264
Where does ubiquinone move?
Within the membrane
265
Where does cytochrome c move?
Intermembrane space
266
Cytochrome c structure?
Heme-containing protein
267
How many electrons does cytochrome c carry?
1
268
Cytochrome c carries electrons to?
Complex IV
269
Color of cytochrome c?
Red
270
How many hemes in Complex IV?
2
271
What happens in Complex IV?
Transfers electrons to oxygen → H2O
272
How many electrons to reduce O2?
4
273
How many H2O per O2?
2
274
How many protons used per 1/2 O2?
2
275
How many protons pumped per O2 by Complex IV?
4
276
How many protons pumped per 1/2 O2?
2
277
Total protons drawn from matrix per O2?
8
278
Complex III receives electrons from?
QH2
279
NADH ETC pathway?
I → III → IV
280
FADH2 ETC pathway?
II → III → IV
281
What happens when electron entry > electron transfer?
Superoxide formation
282
How correct superoxide formation?
SOD and glutathione peroxidase
283
Why RBCs sensitive to oxidative stress?
No mitochondria → no SOD
284
EC gradient creation by active transport?
Complex I & IV
285
Chemical removal?
Reduction of Q and O2
286
Release of protons?
Oxidation of QH2
287
ATP synthase function?
Uses proton gradient to make ATP
288
Functional units of ATP synthase?
F0 and F1
289
N side?
Matrix
290
P side?
Intermembrane space
291
F0?
Proton channel
292
F1?
Catalyzes ATP formation
293
F1 states?
Open (empty); Loose (binds ADP+Pi); Tight (forms ATP)
294
Protons per ATP?
3
295
What causes ATP burst?
Addition of succinate + ADP + Pi
296
What blocks transfer to O2?
CN–
297
Oligomycin?
Inhibits ATP synthase
298
DNP?
Uncoupler
299
Valinomycin?
K+ ionophore
Reduces charge gradient of the ETC
is a cyclic peptide antibiotic that acts as a potassium-selective ionophore, meaning it carries K+ ions across biological membranes, disrupting ion gradients and cell function; it's highly effective due to its structure (hydrophilic core, hydrophobic exterior) allowing it to shuttle K+ through lipid bilayers
300
Thermogenin?
Uncoupling protein in brown fat
301
ETC inhibitors?
CN–
302
ATP synthase inhibitor?
Oligomycin
303
Uncouplers?
DNP
304
Secret proton?
4th proton needed for transport processes
305
Cotransporter?
Moves molecules of opposite charges together
306
Antiporter?
Swaps molecules in opposite directions
307
Malate-aspartate shuttle ATP yield?
38 ATP
308
Glycerol 3-P shuttle ATP yield?
36 ATP
309
Regulator of oxidative phosphorylation?
NADH (and ADP/Pi)
310
Energy measure of the cell?
ADP concentration
311
Mass-action ratio?
[ATP]/([ADP][Pi])
312
How far back does NADH inhibit?
PFK-1
313
Mito role in apoptosis?
Release of cytochrome c triggers caspases
314
Mito genome size?
37 genes
315
Do mitochondria have ribosomes?
Yes
316
Mitochondrial DNA inherited from?
Maternal
317
Mito mutation in Type I diabetes?
Low ATP in pancreatic cells → no insulin release
318
What is neuronal signaling?
Short distance
Release neurotransmitter
Act on nearby cell
Also called synaptic signaling; a neurotransmitter crosses the synapse to target cell and starts transduction (<1 µm)
319
What is hormonal signaling?
Hormones carried by blood to cells and organs (large distances)
320
Do different cells have different receptors for hormones?
Yes
321
Can the same hormone receptor have different downstream effects?
Yes
322
What are the cell surface hormonal receptor types?
Metabotropic
323
What are metabotropic receptors?
Hormone receptors that act through a second messenger system
324
What are ionotropic receptors?
Hormone receptors that are coupled to ion channels
325
Are receptor-hormone interactions high or low affinity?
High affinity
326
Why are receptor-hormone interactions high affinity?
So only low concentrations of hormone are required to cause an effect
327
What are nuclear receptors?
Receptors in nucleus for steroid/thyroid hormones
328
What are downstream effects of hormone signaling?
- Secondary messenger activation (cAMP, IP3)
- Receptor Tyrosine Kinase activation
- Hormone-gated ion channels open/close altering membrane potentials
- Adhesion receptors send info to cytoskeleton
- Steroid hormones bind nuclear receptors causing gene expression
329
What are the three classes of mammalian hormones?
Paracrine
330
What are endocrine hormones?
Chemicals secreted by endocrine glands directly into the blood
331
Examples of endocrine hormones
Insulin and glucagon
332
What are paracrine hormones?
Released into extracellular space and diffuse to neighboring cells/tissues (lipophilic/hydrophobic)
333
Example of paracrine hormones
Eicosanoids
334
What are autocrine hormones?
Local hormones that are secreted and bind to the same cell
335
Peptide and amide hormones bind where?
Extracellularly
336
Peptide hormone examples
Insulin (Beta cell)
337
Amine hormone example
Epinephrine
338
Peptide and amide hormone binding result in what?
Signal amplification
339
What is insulin initially secreted as?
Preproinsulin
340
How many disulfide bonds are in insulin?
3
341
Why can we use insulin from pigs?
It has 51 amino acids and is structurally similar
342
Where is insulin stored?
Secretory vesicles in beta cells
343
How does changing the order of the AA sequence of insulin change its effects?
Can make insulin fast acting or long acting
344
Lispro (Humalog) type?
Rapid-acting insulin
345
What is the issue with animal-derived insulin?
Eventual immunogenic resistance
346
Lack of insulin causes what?
Diabetes mellitus type 1
347
Rapid-acting human insulin analogs
Lispro (Humalog)
348
Long-acting human insulin analogs
Glargine (Lantus
349
Ultra-long acting insulin
Degludec (Tresiba) >40 hours
350
Catecholamine hormones
Epinephrine and norepinephrine
351
Where are catecholamines synthesized?
Adrenal medulla
352
Catecholamines are derived from?
Tyrosine
353
Where do catecholamines bind?
Extracellular receptors which utilize secondary messengers
354
Paracrine hormones include?
Prostaglandins
355
Eicosanoid examples
Prostaglandins
356
Paracrine hormones are derived from?
Arachidonic acid (via phospholipase A2)
357
Where do paracrine hormones act?
Locally
358
Role of paracrine hormones?
Inflammation
359
Where is testosterone produced?
Testes
360
Where is estradiol produced?
Ovaries
361
Where are cortisol and aldosterone produced?
Adrenal glands
362
How are steroid hormones transported?
Bound to plasma proteins (albuminmum)
Cross 3 membrane
363
Steroids are derived from?
Cholesterol
364
Where do retinoid hormones bind?
Nuclear receptors
365
Retinoid hormones are derived from?
Vitamin A (retinol / cleavage of B-carotene)
366
Do all cells have at least one form of retinoid receptor?
Yes
367
What does retinoic acid do hormonally?
Regulates genes governing cell growth and differentiation
368
What does all-trans-retinal do?
Relays neuronal signals (vision)
369
Where are retinoids most active?
Cells undergoing rapid growth: lung epithelia
370
Where do thyroid hormones bind?
Nuclear receptors
371
How many iodines does T3 have?
3
372
How many iodines does T4 have?
4
373
What is the precursor for thyroid hormones?
Thyroglobulin
374
How is T3 formed?
Conversion of T4
375
What do thyroid hormones cause?
Increase expression of genes that yield energy
376
Lack of iodine in the diet causes what?
Enlargement of thyroid; goiter
377
What kind of receptor does nitric oxide interact with?
Intracellular receptor
378
What is nitric oxide made from?
Arginine (via O2 and NO synthase)
379
What does nitric oxide do?
- Activates guanylyl cyclase, increasing cGMP
- Relaxation of contractile proteins in smooth muscle
- Lowers blood pressure
380
What is cGMP?
Cyclic Guanosine Monophosphate; second messenger
381
Major endocrine glands
Hypothalamus, pituitary, thyroid, parathyroid, adrenal glands, pancreas, pineal gland, and the gonads (ovaries in females, testes in males)
382
Top-down hormonal signaling
Signals originating in brain
383
Examples of top-down signaling
Oxytocin
384
Bottom-up signaling
Signals originating elsewhere in the body
385
Examples of bottom-up signaling
Epinephrine (adrenaline)
386
Do muscles store large or small amounts of glycogen?
Small (1–2%)
387
Is heart muscle aerobic or anaerobic?
100% aerobic
388
Energy sources in muscles for bursts of activity?
Muscle glycogen (produces lactate)
389
Energy sources for light activity or rest?
Fatty acids as its main energy source, supported by carbohydrates, with a small contribution from protein
390
During heavy muscle use, oxygen consumption
oxygen consumption can increase 10 to 20 times above resting levels, with active muscles extracting up to 70-80% of the delivered oxygen, compared to 20-40% at rest
391
What is the Cori cycle?
Cycle of lactate to glucose between muscle and liver; ATP produced as glycogen is broken down; ATP used to convert lactate to glucose
392
Brain metabolism uses what?
Glucose except in prolonged starvation (ketolysis)
393
ATP in brain metabolism also contributes to?
Action potentials for neurons
394
What is electrogenic transport?
the movement of ions across a cell membrane that results in a net change of electrical charge, creating a voltage difference (membrane potential)
sodium-potassium pump (Na+/K+ ATPase), which pumps 3 Na+ ions out for every 2 K+ ions in,
395
Well-fed state insulin and metabolism?
Insulin secretion is high and anabolic metabolism prevails
396
Normal blood glucose range
70–99 mg/dL
397
Blood glucose 40 mg/dL
Lethargy
398
Blood glucose of 10 mg/dL
Permanent brain damage
399
What does insulin do to muscles?
Facilitates glucose uptake
400
What does insulin do to liver?
Promotes glycogen synthesis
401
What does insulin do to adipocytes?
Promotes glycerol synthesis and inhibits fat breakdown
402
What regulates release of insulin?
Glucose and ATP levels
403
High glucose effect on ATP concentration?
High ATP levels
404
High ATP levels inhibit what?
K+ efflux (which triggers Ca2+ influx and insulin release)
405
What is Amylin?
Small polypeptide stored and secreted with insulin; regulates post-prandial glucose
406
Post-prandial means?
After a meal
407
How does amylin affect glucose concentrations?
1. Slows gastric emptying
2. Suppresses postprandial glucagon secretion
3. Centrally-mediated appetite modulation
408
Amylin in diabetes?
Absent in Type 1
409
Decreased Amylin causes?
Hyperglycemia and weight gain
410
Pramlintide (Symlin)
Amylin analog
411
Fasting state timelines
2–3 h: glycogenolysis
4–6 h: gluconeogenesis
>30 h: major glycogen depletion, glucose from gluconeogenesis
412
ATP equivalents
Total ATP produced per mole of substrate oxidized
413
ATP from glucose
38 ATP
414
Average FA ATP production
144 ATP
415
Ketone bodies ATP production
Acetoacetate: 23 ATP
416
Carbohydrate caloric value
4 kcal/g
417
Protein caloric value
4 kcal/g
418
Fat caloric value
9 kcal/g
419
Metabolism in prolonged fasting or Type 1 Diabetes?
- Starvation state induced
- Fat stores primary energy source
- Glycogen depletion
- Ketone bodies increase
- Blood glucose decrease
- Insulin output decreases
- Glucagon output increases
420
Classic symptoms of Type 1 Diabetes
Polydipsia
421
IDDM
Type 1 Diabetes
422
NIDDM
Type 2 Diabetes
423
GLP-1 agonists
Exenatide
424
GLP-1 agonist MOA
- Increase glucose-dependent insulin secretion
- Promote B-cell proliferation
- Decrease glucagon secretion
- Slow gastric emptying
425
DPP-IV inhibitors
Sitagliptin
426
DPP-IV inhibitors MOA
Delay breakdown of incretin hormones by inhibiting DPP-IV
427
Incretin definition
Hormone from intestine that increases insulin synthesis/release
428
Meglitinides
Repaglinide
429
Meglitinides MOA
Stimulate rapid/short-lived insulin release by binding beta-cell ATP-dependent K+ channels
430
Leptin
Hormone from adipose; acts as satiety factor on hypothalamus; antagonizes Ghrelin and NPY
431
Ghrelin
Hunger-arousing hormone from empty stomach
432
Neuropeptide Y (NPY)
Secreted by gut; stimulates feeding
433
Adiponectin effect
Increases insulin sensitivity
434
Resistin effect
Decreases insulin sensitivity
435
Adiponectin with obesity
Decreases
436
Resistin with obesity
Increases
437
Energy expenditure depends on
1. Basal metabolic rate
2. Thermogenic effect
3. Physical activity
4. Environmental temperature
438
Recommended carbohydrate intake
0.58
439
Recommended protein intake
0.12
440
Recommended fat intake
30% (10% poly
441
B1 deficiency
Beriberi
442
B2 deficiency
Riboflavin
443
B6 function
Transamination and decarboxylation reactions
444
B3 (Niacin) deficiency
Pellagra
445
Biotin function
Carboxylation reactions
446
B5 (Pantothenic acid) function
Component of coenzyme A and ACP
447
ACP
Acyl carrier protein
448
B9 (Folic acid) function
Carbon transfer
449
Vitamin C (ascorbic acid) deficiency
Scurvy
450
Lipoic acid function
Acyl and redox carrier
451
Vitamin A function
Vision
452
Vitamin D deficiency
Rickets
453
Vitamin E function
Antioxidant
454
Vitamin K function
Blood clotting
455
B12 (Cobalamin) deficiency
Pernicious anemia
456
How many AAs are needed for protein synthesis?
All essential amino acids
457
Nutritional value of protein
Essential AA content and digestibility
458
Chemical score of protein
Potential value
459
Biological value of protein
How quickly nitrogen can be synthesized into body protein; inversely related to amount needed to obtain limiting AA
460
Biological value of 100
Provides all essential AAs in proper proportions
461
If a protein is completely deficient in one AA
chemical score?
462
Excess AA from low-score protein?
Converted to glycogen
463
Do plant proteins contain all essential AAs?
No; must be combined with other foods
464
One pound of body fat equals how many calories?
3500
465
Extra calories to accumulate 25 pounds over 18 months?
150 kcal/day
466
What is the first step in Amino Acid synthesis?
Transamination
467
What is glutamine made from?
Glutamate
468
How much ATP does it take to turn glutamate into glutamine?
1 ATP
469
What process creates a good leaving group that can be displaced by ammonia?
Phosphorylation of Glutamate
470
What kinds of amino acids are made from ammonia and a-keto acids?
Non-essential
471
Pyrimidines
Cytosine and Thymine
472
Purines
Adenine and Guanine
473
GMP
Guanosine monophosphate
474
AMP
Adenosine monophosphate
475
IMP
Inosine monophosphate
476
UMP
Uridine monophosphate
477
TMP
Thymidine monophosphate
478
Inosine monophosphate
Parent purine nucleotide
479
What is the cofactor used in transamination?
PLP (B6)
480
Can PLP help with catabolism or anabolism?
Both
481
Where does the Histidine skeleton come from?
Ribose 5-phosphate
482
Where do the Serine, Glycine and Cysteine skeletons come from?
3-phosphoglycerate
483
Where do the Tryptophan, Phenylalanine, and Tyrosine skeletons come from?
Erythrose 4-phosphate and phosphoenolpyruvate
484
Where do Alanine, Valine, Leucine and Isoleucine skeletons come from?
Pyruvate
485
Where do Aspartate, Asparagine, Methionine, Threonine and Lysine skeletons come from?
Oxaloacetate
486
Where do Glutamate, Glutamine, Proline and Arginine skeletons come from?
a-ketoglutarate
487
Which pathway is responsible for creating intermediates that form non-essential amino acids?
All of them
488
What cofactor does Tyrosine need to become Dopa?
Tetrahydrobiopterin
489
Tetrahydrobiopterin
Stabilizes hydroxylases
490
What can Tyrosine be converted to?
L-dopa, Dopamine, Norepinephrine, Epinephrine
491
What can Glutamate be converted to?
GABA
492
What can Histidine be converted to?
Histamine
493
The conversion of Dopa to Dopamine, Glutamate to GABA, Histidine to Histamine, and 5-hydroxytryptophan to Serotonin undergoes what reaction?
Decarboxylation via PLP-dependent enzymes
494
What cofactor is needed to convert Tryptophan into 5-hydroxytryptophan?
Tetrahydrobiopterin
495
What can Tryptophan be converted into?
Serotonin
496
Porphyrins
A group of light-sensitive, pigmented, ringed chemical structures required for hemoglobin synthesis
497
What are the beginning reagents of porphyrin synthesis?
Succinyl-CoA + Glycine
498
What enzyme converts Succinyl-CoA and Glycine to 2-aminolevulinic acid?
ALA synthase
499
What is removed by ALA synthase in porphyrin synthesis?
CoA-SH + CO2
500
How is Porphobilinogen formed?
Porphobilinogen synthase combines 2 aminolevulinic acids
501
Protoporphyrin IX
Heme without iron
502
Porphyria
Deficiency in enzymes needed to form heme groups, causing precursor buildup in RBCs, body fluids, and tissues
503
Accumulation of uroporphyrinogen (porphyria cutanea tarda)
Pink/purple urine, teeth red fluorescence with UV light, skin sensitive to UV, craving for heme
504
Heme is first degraded into biliverdin by
Heme oxygenase
505
Biliverdin is degraded into bilirubin by
Biliverdin reductase
506
How is bilirubin transported?
Bound to albumin
507
UDP-glucuronosyltransferase
Enzyme for unconjugated -> conjugated bilirubin; essential for excretion
508
Jaundice is caused by
Bilirubin buildup
509
What can cause bilirubin buildup?
Liver disease, blocked bile secretion, lack of UDPGT
510
Where is bilirubin conjugated?
Liver
511
Infant jaundice phototherapy
Uses blue light to convert 4Z,15Z to 4Z,15E (soluble, non-toxic)
512
PRPP
5-phosphoribosyl-1-pyrophosphate; first molecule in purine synthesis; takes amide from glutamine
513
Glutamine-PRPP amidotransferase
Rate-limiting step of purine synthesis (1st step)
514
Simple MOA for purine synthesis
1. Sugar (PRPP) 2. Add units 3. Form complete nucleotide
515
Inosinate (IMP)
First intermediate with complete purine ring
516
Inosinate can be converted to
AMP or GMP
517
Why do some cancer drugs target purine synthesis?
Blocking nucleotide creation stops tumor growth
518
6-mercaptopurine (6-MP), 6-thioguanine (6-TG)
Block de novo purine synthesis at rate-limiting step
519
Pyrimidine synthesis starts with
Aspartate and Carbamoyl phosphate
520
What is formed first in pyrimidine synthesis, UMP or UTP?
UMP
521
What is formed first in pyrimidine synthesis, UTP or CTP?
UTP
522
What is formed last in pyrimidine synthesis?
CTP
523
How many ATP required for pyrimidine synthesis?
2 ATP
524
Is CTP an allosteric activator or inhibitor?
Inhibitor
525
What are precursors for deoxyribonucleotides?
Ribonucleotides
526
Ribonucleotide reductase (RNR)
Converts ribonucleotides to deoxyribonucleotides; requires 2 free SH groups; reductions on NDPs; converts all 4 except UMP; uses NADPH via Glutathione and FAD+
527
dTMP
Deoxythymidine monophosphate
528
dUMP
Deoxyuridine monophosphate
529
Thymidylate synthase
Converts dUMP to dTMP (adds methyl group)
530
Thymidylate synthase cofactor
Tetrahydrofolate (methyl donor)
531
How is THF regenerated?
1. DHFR (NADPH+H) 2. Serine hydroxymethyl transferase (PLP)
532
5-fluorouracil (5-FU), floxuridine, capecitabine
Directly and irreversibly block thymidylate synthase
533
Methotrexate
Blocks DHFR; highly toxic
534
Salvage pathway
Recycles free bases and nucleosides from nucleic acid breakdown; excess is catabolized
535
HGPRT
Converts Hypoxanthine to IMP and Guanine to GMP; major part of salvage pathway
536
Purine catabolism steps
1. Dephosphorylation 2. Deamination to xanthine 3. Oxidation to uric acid 4. Excretion
537
Lesch-Nyhan syndrome
Total lack of HGPRT; intellectual disability, orange sand-like crystals in infants' diapers
538
Excess uric acid causes
Gout and kidney stones
539
Gout
Swollen, red, painful joints (usually toes), mostly males
540
Causes of gout
Excess uric acid production, impaired renal excretion, fructose overconsumption, HGPRT deficiency, purine-rich foods
541
Treatment of gout
Avoid purine-rich foods/fructose; xanthine oxidase inhibitors
542
Allopurinol (Zyloprim), Febuxostat (Uloric)
Xanthine Oxidase (XO) competitive inhibitors
543
Porcine uric acid oxidase
Enzyme from pigs (uricase)
544
Krystexxa (Pegloticase)
IV recombinant uricase; converts uric acid to allantoin; do not use with XOI
545
Catabolism of pyrimidines
Leads to NH4+ then urea and succinyl-CoA via methylmalonyl-semialdehyde; less room for error than purines
546
Coumarins
Novobiocin, coumertcin A1
547
Coumarins MOA
Inhibit bacterial type II topoisomerases from binding ATP
548
Quinolones
nalidixic acid, ciprofloxacin
549
Quinolones MOA
Inhibit resealing of DNA
550
Eukaryotic Type I topoisomerase inhibitors
Captothecin, irinotecan (Campto), topotecan (Hycamtin)
551
Eukaryotic Type I topoisomerase inhibitors MOA
Trap the enzyme-DNA complex in its cleaved state
552
Eukaryotic Type II topoisomerase inhibitors
Doxorubicin (Adriamycin), etoposide (Etopophos), ellepticine
553
Eukaryotic Type II topoisomerase inhibitors MOA
Intercalators (insert between base pairs)
554
Nitrogenous mustards MOA
Alkylation of DNA, attaches to both strands (blocking synth/repair)
555
RNA polymerase inhibitors
Acinimycin D, acridines, Rifamicin
556
Tetracycline MOA
Inhibit protein synthesis in ribosome (bacteriostatic)
557
Chloramphenicol MOA
Inhibits protein synthesis in ribosomes (block peptidal transfer)
558
Streptomycin MOA
Misreading of genetic code
559
Diptheria toxin
Highly toxic in humans, inhibits protein synthesis
560
Ricin toxin
From Castor beans, inhibits protein synthesis
561
Cycloheximide
Blocks the translocation reaction on ribosomes
562
Puromycin
Causes premature chain termination
563
a-amantin
Inhibits RNA pol II and III of predators; from toxic mushrooms
564
Rifampicin
Inhibits RNA polymerase via beta subunit
565
Diagnostic markers for Hepatitis & Cirrhosis?
Elevated ALT (GPT) and AST (GOT).
566
What is Azotemia?
High levels of nitrogen-containing compounds (Urea, Creatinine) in the BLOOD (High BUN).
567
What is Azoturia?
Excess nitrogenous compounds in the URINE.
568
What is Asterixis (Liver Flap)?
Flapping tremor caused by Ammonia toxicity (Hyperammonemia) affecting the brain.
569
Cause of Phenylketonuria (PKU)?
Deficiency of Phenylalanine Hydroxylase (cannot convert Phe to Tyr).
570
Drug: Sapropterin (Kuvan®)?
Synthetic BH4 (cofactor) used to treat Phenylketonuria (PKU).
571
Cause of Maple Syrup Urine Disease (MSUD)?
Defect in Branched-Chain Alpha-Ketoacid Dehydrogenase (cannot breakdown Leu, Ile, Val).
572
Cause of Ornithine Transcarbamoylase (OTC) Deficiency?
X-linked Urea Cycle defect; causes hyperammonemia and accumulation of Orotic Acid.
573
Condition: Hyperhomocystinemia?
High Homocysteine levels (risk factor for CVD); often due to Folate (B9), B12, or B6 deficiency.
574
Drug: Pyridoxal Phosphate (PLP/Vitamin B6)?
Co-enzyme for Transaminases; deficiency causes sideroblastic anemia and convulsions.
575
Drug: Lactulose?
Non-absorbable sugar; acidifies gut to trap Ammonia (NH3 -> NH4+) to treat Hepatic Encephalopathy.
576
Essential Amino Acids (Mnemonic)?
PVT TIM HALL (Phe, Val, Thr, Trp, Ile, Met, His, Arg, Leu, Lys).
577
Drug: Sulfonamides (e.g., Sulfamethoxazole) MOA?
Inhibits Bacterial Dihydropteroate Synthase (mimics PABA).
578
Drug: Trimethoprim MOA?
Inhibits Bacterial Dihydrofolate Reductase (DHFR).
579
Drug: Bactrim® composition & use?
Sulfamethoxazole + Trimethoprim; used for sequential blockage of folate synthesis.
580
Vitamin: Cobalamin (B12)?
Required for Methionine Synthase and Methylmalonyl-CoA Mutase; deficiency = Pernicious Anemia.
581
Condition: Hypercholesterolemia?
High LDL cholesterol; risk factor for Atherosclerosis.
582
Drug Class: Statins (Lovastatin/Mevacor, Rosuvastatin/Crestor) MOA?
Competitive inhibitors of HMG-CoA Reductase (Rate-limiting step of cholesterol synthesis).
583
Drug: Cholestyramine (Questran®) MOA?
Bile Acid Sequestrant (binds bile in gut, forces liver to use cholesterol to make more).
584
Drug: Fenofibrate (Tricor®) MOA?
PPAR-alpha agonist (increases Lipoprotein Lipase, lowers VLDL/Triglycerides).
585
Drug: Niacin (Vitamin B3/Nicotinic Acid) lipid effect?
Inhibits lipolysis in adipose tissue; reduces VLDL production (raises HDL).
586
Drug: Omacor® composition?
Omega-3 Fatty Acids (EPA + DHA); lowers triglycerides.
587
Essential Fatty Acids?
Linoleic Acid (Omega-6) and Alpha-Linolenic Acid (Omega-3).
588
Lab Analysis: Chylomicrons?
Transport DIETARY lipids from intestine to tissues.
589
Lab Analysis: VLDL?
Transports ENDOGENOUS lipids from liver to tissues.
590
Lab Analysis: LDL vs HDL?
LDL delivers cholesterol to cells (Bad); HDL transports cholesterol back to liver (Good).
591
Glucagon Glycogen Glucose Gluconeogensis Glucolysis
When blood sugar drops, glucagon is released, activating glycogenolysis (glycogen to glucose) and gluconeogenesis (making new glucose) while blocking glycolysis (glucose breakdown) to ensure cells have fuel.
Glucose: A simple sugar (monosaccharide) that is the body's primary source of energy, absorbed from food and used directly or stored.
Glycogen: A complex carbohydrate (polysaccharide) made of many glucose units, serving as the main short-term energy storage form in the liver and muscles.
Glucagon: A peptide hormone (from the pancreas) that raises blood glucose by signaling the liver to break down glycogen and synthesize new glucose.
Glycogenolysis: The metabolic process of breaking down stored glycogen into individual glucose molecules.
Gluconeogenesis: The metabolic pathway that creates glucose from non-carbohydrate precursors (like amino acids, lactate, or fats) in the liver and kidneys, crucial when glucose is scarce.
Glycolysis: The metabolic pathway that breaks down one molecule of glucose into pyruvate, producing energy (ATP) and intermediates for other uses
592
Disease: Porphyrias?
Genetic defects in Heme biosynthesis; accumulation of toxic porphyrin precursors.
593
Disease: Crigler-Najjar Syndrome?
Deficiency in UDP-Glucuronyl Transferase (cannot conjugate bilirubin -> severe jaundice).
594
Disease: Gout?
Accumulation of Uric Acid crystals in joints.
595
Drug: Allopurinol (Zyloprim) MOA?
Inhibits Xanthine Oxidase (Purine analog).
596
Drug: Febuxostat (Uloric) MOA?
Inhibits Xanthine Oxidase (Non-purine).
597
Drug: Krystexxa (Pegloticase/Uricase) MOA?
Recombinant Uricase; converts Uric Acid to Allantoin (soluble).
598
Drug: Methotrexate MOA?
Inhibits Human Dihydrofolate Reductase (Anticancer/Immunosuppressant).
599
Drug: 5-Fluorouracil (5-FU) MOA?
Suicide inhibitor of Thymidylate Synthase (blocks dTMP synthesis).
600
Drug: Capecitabine?
Oral prodrug of 5-FU.
601
Drug: 6-Mercaptopurine / 6-Thioguanine MOA?
Purine antagonists; inhibit purine nucleotide synthesis.
602
Disease: Type 1 Diabetes (IDDM)?
Autoimmune destruction of Beta-cells; Absolute insulin deficiency.
603
Disease: Type 2 Diabetes (NIDDM)?
Insulin resistance + relative deficiency.
604
Deficiency Disease: Scurvy?
Vitamin C deficiency (collagen synthesis defect).
605
Deficiency Disease: Rickets?
Vitamin D deficiency (bone mineralization defect).
606
Deficiency Disease: Beri-Beri?
Thiamine (B1) deficiency.
607
Deficiency Disease: Pellagra?
Niacin (B3) deficiency (Dermatitis, Diarrhea, Dementia).
608
Deficiency Disease: Pernicious Anemia?
Vitamin B12 absorption defect (lack of Intrinsic Factor).
609
Deficiency Disease: Goiter?
Iodine deficiency (Thyroid enlargement).
610
Drug: Rapid-Acting Insulins?
Lispro, Aspart, Glulisine.
611
Drug: Long-Acting Insulins?
Glargine, Detemir.
612
Drug: Ultra Long-Acting Insulin?
Degludec.
613
Drug: Pramlintide?
Amylin analog (slows gastric emptying).
614
Drug Class: GLP-1 Agonists (Exenatide, Liraglutide, Semaglutide) MOA?
Incretin mimetics: Increase insulin, decrease glucagon, slow gastric emptying.
615
Drug Class: DPP-IV Inhibitors (Sitagliptin, Saxagliptin) MOA?
Inhibit the enzyme that breaks down GLP-1 (increases endogenous GLP-1 levels).
616
Drug Class: Meglitinides (Repaglinide) MOA?
Stimulate pancreatic insulin release (short acting).
617
Drug Class: Quinolones (Ciprofloxacin, Nalidixic Acid) MOA?
Inhibit Bacterial DNA Gyrase (Topoisomerase II).
618
Drug Class: Coumarins (Novobiocin) MOA?
Inhibit Bacterial DNA Gyrase (ATPase subunit).
619
Drug: Camptothecin / Irinotecan / Topotecan MOA?
Inhibit Eukaryotic Topoisomerase I.
620
Drug: Doxorubicin / Etoposide MOA?
Inhibit Eukaryotic Topoisomerase II.
621
Drug: Rifampicin (Rifadin) MOA?
Inhibits Bacterial RNA Polymerase (Transcription).
622
Drug: Actinomycin D MOA?
Intercalates DNA; blocks Transcription (both pro- and eukaryotic).
623
Drug: Alpha-Amanitin MOA?
Potent inhibitor of Eukaryotic RNA Polymerase II (Death cap mushroom).
624
Drug: Tetracyclines MOA?
Bind 30S Ribosome (blocks A-site).
625
Drug: Streptomycin (Aminoglycoside) MOA?
Binds 30S Ribosome (causes code misreading).
626
Drug: Chloramphenicol MOA?
Binds 50S Ribosome (inhibits Peptidyl Transferase).
627
Drug: Puromycin MOA?
Mimics aminoacyl-tRNA; causes premature chain termination.
628
Toxin: Diphtheria Toxin MOA?
Inactivates eEF-2 (stops translocation in Eukaryotes).
629
Toxin: Ricin MOA?
Inactivates 60S ribosomal subunit (depurinates rRNA).
630
Jaundice is caused by accumulation of what?
Bilirubin
631
Which statement is true regarding gout?
It can be controlled by inhibiting xanthine oxidase
632
Biosynthesis of purines can be blocked by which compound?
6-thioguanine
633
Atherosclerosis and Coronary Heart Disease is associated with which lipid level?
Low HDL
634
Fatty acid synthesis is inhibited by which molecule?
Palmitoyl-CoA
635
The glutamine biosynthesis from glutamate involves which enzyme?
Glutamine synthetase
636
What molecule provides energy for glutamine synthesis from glutamate?
ATP
637
What molecule provides nitrogen for glutamine synthesis from glutamate?
NH4+
638
Which amino acid is the substrate for glutamine synthesis?
Glutamate
639
Which lipoprotein contains the greatest amount of cholesterol?
LDL
640
Which compound inhibits ATP synthase?
Oligomycin
641
Which compound is an uncoupling agent?
2
642
Entry of acetyl-CoA into the citric acid cycle is decreased when?
The ratio of [ATP]/[ADP] is high
643
Which uncoupler is relevant in newborns?
Thermogenin
644
How many ATP molecules are used to generate one molecule of urea?
4
645
Asterixis (liver flap) is directly related to high concentrations of which molecule in the brain?
Glutamate
646
Urea contains two nitrogen atoms. One comes from ammonia the other from?
amino acid aspartate,
647
Which amino acids are both ketogenic and glucogenic?
Isoleucine
648
Mobilization of fats from adipose tissue involves which proteins and hormones?
Perilipin
649
Mobilization of fats from adipose tissue does NOT involve?
Transport of fats through the adipocyte membrane
650
Bile salts are used to do what?
Emulsify fats in the small intestine and solubilize them
651
In the small intestine fats are broken down into?
fatty acids and glycerol by enzymes like lipase.
652
Chylomicrons are the main vesicles used for what?
Transport of fats in the bloodstream
653
Fatty acids are transported from adipose tissue to other tissues via?
Albumin
654
Which enzymes/cofactors/substrates are involved in transporting fatty acids to mitochondria?
ATP
655
The first step of ketone body production from acetyl-CoA is catalyzed by which enzyme?
Thiolase
656
A person with uncontrolled diabetes will NOT display which condition?
Metabolic alkalosis
657
A person with uncontrolled diabetes will display what signs?
Labored breathing
658
Which drug decreases beta-1 3-glucan production and can be given orally?
Ibrexafungerp (brand name Tivdak
beta-1,3-glucans (β-glucans), derived from sources like yeast and fungi, can be given orally and are studied for immune suppo
659
Which enzyme is NOT involved in degradation of ingested proteins to amino acids?
Thrombin
660
Which enzymes ARE involved in degradation of ingested proteins to amino acids?
Pepsin
661
Which statements are true regarding transamination reactions?
Catalyzed by aminotransferases; allow transfer of amino group from amino acid to ketoacid; L-glutamate acts as temporary storage of nitrogen
662
Which statement regarding transamination reactions is false?
Use biotin as cofactor
663
Cancer growth can be inhibited through the use of which drug?
5-fluorouracil
664
Which compound is NOT a metabolic precursor of amino acids?
Glucose-6-phosphate
665
Which compounds are metabolic precursors of amino acids?
3-phosphoglycerate
666
d-Aminolevulinic acid is formed from succinyl-CoA and which amino acid?
Glycine
667
d-Aminolevulinic acid is an intermediate in the biosynthesis of?
Porphyrins
668
Acetyl CoA for fatty acid synthesis is generated by which enzyme?
Citrate lyase
669
Which component is part of acyl carrier protein (ACP)?
Pantothenic acid
670
A decarboxylase is NOT involved in the biosynthesis of which molecule?
Glutamine
671
Which electron transport complex has enzyme activity shared with the Krebs cycle?
Complex II
672
Which electron transfer is NOT accompanied by proton pumping and ATP production?
Succinate dehydrogenase (Complex II)
673
Which electron transfers ARE accompanied by proton pumping and ATP production?
Cytochrome c to O2
674
How many protons are pumped by Complex IV per O2 molecule?
4
675
How many protons translocate through ATPase to make 3 ATP molecules?
9
676
In Complex III electrons are passed from?
electrons are passed from ubiquinol (QH2) (reduced coenzyme Q) and ultimately donated to cytochrome c, with some electrons recycled back to ubiquinone in the Q-cycle, generating a proton gradient for ATP synthesis.
677
Which of the following is NOT specifically required in fatty acid synthesis?
Malate
678
Which molecules ARE specifically required in fatty acid synthesis?
Biotin
Med Chem
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