Metabolism Flashcards
(90 cards)
1
Q
Mitochondria reactions
A
BOAT - B-oxidation, Oxidative phosphorylation, Acetyl-coA production, and TCA cycle
2
Q
Cytoplasm and mitochondria reactions
A
HUGs take two (Heme synthesis, Urea cycle, Gluconeogenesis)
3
Q
Glycolysis rate limiting enzyme
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PFK-1 — increased by AMP and fructose-2,6-bisphosphate — decreased by ATP and citrate
4
Q
Gluconeogenesis rate limiting enzyme
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Fructose - 1,6-bisphosphatase – increased by ATP and acetyl-coA — decreased by AMp and fructose-2,6-bisphosphate
5
Q
TCA cycle rate limiting enzyme
A
Isocitrate dehydrogenase – increased by ADP – decreased by ATP and NADH
6
Q
Glycogenesis rate limiting enzyme
A
Glycogen synthase – increased by G6P, insulin, cortisol — decreased by epinephrine, glucagon
7
Q
Glycogneolysis rate limiting enzyme
A
Glycogen phosphorylase – increased by epinephrine, glucagon, and AMP — decreased by G6P, insulin, ATP
8
Q
HMP shunt rate limiting enzyme
A
G6PD - increased by NADP — decreased by NADPH
9
Q
De novo purine synthesis rate limiting enzyme
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PRPP – decreased by AMP, inosine monophosphate, and GMP
10
Q
De novo pyrmidine synthesis rate limiting enzyme
A
Carbamoyl phosphate synthetase II — increased by ATP, decreased by UTP
11
Q
Urea cycle rate limiting enzyme
A
Carbamoyl phosphate synthetase I — increased by N-acetylglutamate
12
Q
Fatty acid synthesis rate limiting enzyme
A
Acetyl-CoA carboxylase — increased by insulin and citrate — decreased by glucagon and palmitoyl CoA
13
Q
Fatty acid oxidation rate limiting enzyme
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Carnitine acyltransferase I — decreased by malonyl-coA
14
Q
Ketogenesis rate limiting enzyme
A
HMG-CoA synthase
15
Q
Cholesterol synthesis rate limiting enzyme
A
HMG-CoA reductase — increased by insulin and thyroxine — decreased by glucagon and cholesterol
16
Q
Heme synthesis rate limiting enzyme
A
Aminoleuvulonate snythase
17
Q
Bile acid synthesis rate limiting enzyme
A
7a-hydroxylase
18
Q
ATP production
A
Aerobic metabolism makes 32 net ATP via malate aspartate shuttle (heart and liver), and 30 net ATP via glycerol-3-phosphate shuttle (muscle) — anaerobic only makes 2 net ATP (erythrocytes)
19
Q
Universal electron acceptors
A
Nicotinamids and flavin molecules — NAD is used in catabolic processes — NADPH used in anabolic processes
20
Q
Hexokinase
A
Located in most tissues except liver and B cells of pancreas — lower Km (higher affinity), lower Vmax (lower capacity) — feedback inhibited by G6P — steady state
21
Q
Glucokianse
A
Liver, B cells of pancreas — higher Km (lower affinity), higher Vmax (higher capacity) — induced by insulin — gene mutation associated with maturity onset diabetes of the young – works at high glucose concentrations
22
Q
Glycolysis reactions that require ATP
A
Glucose to G6P (G6P inhibits hexokinase, F6P inhibits glucokinase) and Fructose-6-P to Fructose-1,6-BP
23
Q
Glycolysis reactions that produce ATP
A
1,3-BPG to 3-PG (and vice versa – Phosphoglycerate kinase) — PEP to pyruvate (Pyruvate kinase – increased by fructose-1,6-BP, decrased by ATP and alanine)
24
Q
Fructose-2,6-BP regulation
A
Fasting state: increased glucagon –> increased cAMP –> increased protein kinase A –> increased FBPase-2, decreased PFK2, less glycolysis and more gluconeogensis
Fed state: increased insulin –> decreased cAMP –> decreased protein kinase A –> decreased FBPase-2, increased PFK2, less gluconeogensis, more glycolysis
25
Pyruvate dehydrogenase complex
Links glycolysis to TCA cycle --- 5 cofactors (Tender Loving Care For Nancy): pyrophosphate (B1, thiamine, TPP), FAD (B2, riboflavin), NAD (B3, niacin), CoA (B5, pantothenic acid), and lipoic acid (inhibited by arsenic) --- complex is activated by exercise --- deficiency leads to buildup of pyruvate leading to increased lactate (via LDH) and alanine (via ALT): neurologic defects, lactic acidosis, increased serum alanine - Tx: increase intake of ketogenic nutrients (lysine and leucine)
26
Pyruvate metabolism
Alanine (alanine aminotransferase requires B6) --- Oxaloacetate (pyruvate carboxylase requires biotin) --- Acetyl-coA (pyruvate dehydrogenase requires B1, B2, B3, B5, lipoic acid) --- Lactate (lactic acid dehydrogenase requires B3)
27
TCA cycle products
3 NADH, 1 FADH2, 2 CO2, 1 GTP per acetyl coA = 10 ATP (all times 2 per glucose) -- all reactions in mitochondria --- order of molecules: Citrate Is Kreb's Starting Substrate For Making Oxaloacetate
28
Electron transport ATP production and poisons
1 NADH (2.5 ATP) and 1 FADH2 (1.5 ATP) --- Electron transport inhibitors (Rotenone, cyanide, antimycin A, CO) --- ATP synthase inhibitors (oligomycin) --- uncoupling agents (increase membrane permeability, leading to decreased proton gradient, no ATP synthesis but heat is produced - 2,4 dinitrophenol - aspirin - thermogenin in brown fat)
29
Gluconeogensis, irreversible enzymes
Pathway Produces Fresh Glucose --- Pyruvate carboxylase (mitochondria), PEP carboxykinase (cytosol), Fructose-1,6-BP (cytosol), Glucose-6-phosphatase (ER) --- occurs mostly in liver --- odd chain fatty acids make 1 propionyl-coA that can enter the TCA and undergo gluconeogenesis (glucose source)
30
HMP shunt
Source of NADPH (glutathione reduction inside RBCs, fatty acid and cholesterol biosynthesis) --- all reactions occur in cytoplasm --- occurs in lactating mammary glands, liver, adrenal cortex, and RBCs --- oxidative (irreversible) has G6P to 2 NADPH and Ribulose-5-P via G6PD ---- Nonoxidative (reversible has Ribulose-5-P to Ribose-5-P, GLyceraldehyde-3-P, Frucose-6-P via Phosphopentose isomerase and transketolases (requires B1)
31
G6PD deficiency
NADPH is necessary to keep glutathione reduced, detoxifies free radicals and peroxides (decreased NADPH in RBCs leads to hemolytic anemia - due to drugs, infection, or fava beans) --- X linked recessive disorder -- Heinz bodies and bite cells
32
Essential fructosuria
Defect in fructokinase - autosomal recessive - benign, asymptomatic -- frucose in blood and urine
33
Fructose intolerance
Deficiency of aldolase B - autosomal recessive -- Fructose-1-P accumulates causing a decrease in phosphate leading to an inhibition of glycogenolysis and gluconeogenesis --- symptoms following fruit, juice, or honey -- urine dipstick will be negative (only tests for glucose) but can see reducing sugar in urine --- Hypoglycemia, jaundice, cirrhosis, vomiting --- decrease fructose and sucrose intake
34
Galactokinase deficiency
Galactitol accumulates, relatively mild, autosomal recessive --- galactose in blood and urine, infantile cataracts
35
Classic galactosemia
Absence of galactose-1-phopshate uridyltransferase --- autosomal recessive -- damage caused by accumulation of toxic substances --- failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability --- exclude galactose and lactose
36
Sorbitol
Traps glucose in the cell via aldose reductase --- can be converted to fructose in liver/ovaries/seminal vesicles via sorbitol dehydrogenase --- Schwann cells, retina, and kindneys have a risk for osmotic damage (cataracts, peripheral neuropathy) due to sorbitol accumulation -- common in chronic diabetics
37
Lactase deficiency
Lactose intolerance --- loss of brush border due to gastroenteritis, autoimmune disease, etc. --- stool has decreased pH and increased osmotic gap, breath shows increased hydrogen content -- osmotic diarrhea - avoid dairy
38
Essential amino acids
Glucogenic (methionine, valine, histidine) --- Glucogenic/ketogenic (isoleucine, phenylalanine, threonine, tryptophan) --- Ketogenic (leucine, lysine)
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Acidic amino acids
Aspartic acid and glutamic acid
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Basic amino acids
Arginine, lysine, histidine
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Urea cycle substrates
Ordinarily, Careless Crappers Are Also Frivolous About Urination --- Excess nitrogen is converted to urea and excreted by kidneys -- any urea cycle disorder has protein restriction as treatment
42
Hyperammonemia
Excess NH4, which depletes aKG leading to inhibiton of TCA cycle, decreased glutamate --> increased glutamine --> astrocyte swelling and dysfunction ---- tremor, slurring of speech, vomiting, cerebral edema -- Tx: limit protein, lactulose (acidify GI tract and trap NH4 for excretion), Rifaximin (decrease colonic bacteria), Benzoate or phenylbutyrate (decrease ammonia levels)
43
N-acetylglutamate syntahse deficiency
Cofactor for carbamoyl phosphate synthetase I --> hyperammonemia --- presents in neonates as poorly regulated respiration and body temp, poor feeding, developmental delay
44
Ornithine transcarbamylase deficiency
x-linked recessive --- excess orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia
45
Phenylalanine convers to
Requires B4 --> Tyrosine (then Thyroxine) --> Dopa (requires B4, then Melanin) --> Dopamine (requires B6) --> NE (requires vitamin C) --> Epi (requires SAM)
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Tryptophan converts to
Niacin with B6 or Serotonin with BH4 and B6
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Histidine converts to
Histamine with B6
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Glycine converts to
Porphyrin with B6 --> Heme
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Glutamate converts to
Glutathione or GABA with B6
50
Arginine converts to
Creatinine, urea, or nitric oxide (BH4)
51
Phenylketonuria
Decreased phenylalanine hydroxylase or BH4 cofactor --- TYROSINE BECOMES ESSENTIAL --- growth retardation, seizures, fair skin, MUSTY BODY ODOR --- Tx: decrease phenylalanine and increase tyrosine in diet, BH4 supplementation --- autosomal recessive -- avoid aspartame (contains phenylalanine) ----- Maternal PKU (microcephaly and congenital heart defects in baby)
52
Maple syrup urine disease
Blocked degradation of branched amino acids (Isoleucine, Leucine, Valine) due to decreased aKG dehydrogenase --- severe CNS defects, intellectual disability, death, burnt sugar urine -- autosomal recessive --- Tx: restriction of branched amino acids, thiamine supplementation
53
Alkaptonuria
Deficiency of homogenistic oxidase in degradative pathway of tyrosine to fumarate -- autosomal recessive -- dark connective tissue, brown pigmented sclerae, urine turns black
54
Homocystinuria
3 types: Cystathionine synthase deficiency (tx: decrease methionine, increase cysteine, B12, and folate) --- Decreased affinity of cystathionine synthase for PRP (tx: HUGELY increase B6 and increase cysteine) --- Homocysteine methyltransferase deficiency (tx: increase methionine) ---- All have increased homocysteine in urine, osteoporosis, intellectual disabilities, lens subluxation (down and in), marfanoid habitus, atherosclerosis, thrombosis
55
Cystinuria
Defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of COLA (Cysteine, Ornithine, Lysine, Arginine) --- hexagonal cysteine stones (excessive cysteine in urine) - urinary cyanide nitroprusside test is postitive --- Tx: urinary alkalinization (potassium citrate) and chelating agents (penicillamine)
56
Glycogen regulation
Gucagon and Epinephrine increase adenylate cyclase --> cAMP --> protein kinase A --> glycogen phosphorylase kinase (also increased by calcium-calmodulin in muscle contraction) --> glycogen phosphorylase --> glucose
Insulin binds to tyrosine kinase dimer --> activates glycogen synthase and protein phosphatase --> glycogen
57
Glycogen
Branches have a(1,6) and linkages have a(1,4) --- skeletal muscle (glycogen undergoes glycogenolysis which is rapidly metabolized during exercise) --- hepatocytes (glycogen is stored and udnergoes glycogenolysis to maintain blood sugar --- requires debranching enzymes to get glucose off -- limit dextrin refers to one of 4 resides remaining on a branch after glycogen phosphorylase
58
Von Gierke disease
Type I glycogen storage disease (deficient glucose-6-phosphatase) - fasting hypoglycemia, LOTS of glycogen in liver, increase blood lactate, increase TGs, increase uric acid) --- Tx: frequent oral glucose/cornstarch
59
Glycogen storage diseases
Very Poor Carbohydrate Metabolism (Von Gierke, Pompe, Cori, McArdle) --- all are autosomal recessive
60
Pompe disease
Type II glycogen storage disease (lysosomal a-1,4-glucosidase deficiency) -- CARDIOMEGALY, exercise intolerance
61
Cori disease
Type III glycogen storage disease (Debranching enzyme) -- normal blood lactate levels, accumulation of small dextrin like material -- gluconeogenesis is intact
62
McArdle disease
Type V glycogen storage disease (Skeletal muscle glycogen phosphorylase) -- increase glycogen in muscle leading to cramps, myoglbinuria, arrhythmias --- blood glucose levels unaffected -- Tx: vitamin B6
63
Fabry disease
a-galactosidase A deficiency -- accumulate ceramide trihexodside -- XR --- severe extremity pain, decreased sweating, GI changes, angiokeratomas
64
Gaucher disease
Glucocerebrosidase deficiency - accumulate glucocerebroside -- AR -- MOST COMMON! no neuro symptoms, hepatosplenomegaly, aseptic necrosis of femur, osteoporosis, Gaucher cells (crumpled tissue paper)
65
Niemann Pick disease
Sphingomyelinase deficiency -- accumulate sphingomyelin -- AR -- hepatosplenomegaly, cherry red spot on macula, foam cells (lipid laden macs), neurodegeneration (loss of motor skills in infant)
66
Tay Sachs disease
Hexosaminidase A deficiency -- accumulate GM2 ganglioside -- AR -- neurodegeneration, cherry red spot on macula, lysosomes with onion skin, NO HEPATOSPLENOMEGALY
67
Krabbe disease
Galactocerebrosidease deficiency -- accumulate galactocerebroside and psychosine -- AR -- peripheral neuropathy, optic atrophy, globoid cells
68
Metachromatic leukodystrophy
Arylsulfatase A deficiency -- accumulate cerebroside sulfate -- central and peripheral demyelination with ataxia
69
Hurler syndrome
a-L-iduronidase deficiency -- accumulate heparan sulfate and dermatan sulfate -- AR -- developmental delay, airway obstruction, corneal clouding, hepatosplenomegaly
70
Hunter syndrome
Iduronate sulfatase deficiency -- accumulate heparan sulfate and dermatan sulfate -- XR -- mild hurler + aggressive but NO CORNEAL CLOUDING (hunters see clearly)
71
Fatty acid synthesis
Requires transport of citrate from mitochondria to cytosol
72
Long chain fatty acid degradation
Requires carnitine dependent transport into mitochondrial matrix --- carnitine deficiency leads to toxic accumulation and hypoketotic hypoglycemia
73
Medium chain acyl-CoA dehydrogenase deficiency
AR disorder of fatty acid oxidation --- accumulation of 8-10 carbon fatty acyl carnitines in blood and hypoketotic hypoglycemia -- fasting leads to hypoglycemia nd decreased ketones
74
Ketone bodies
In alcoholism, excess NADH shunts oxaloacetate to malate --- prolonged starvation and DKA leads to oxaloacetate depletion --- both lead to buildup of acetyl-CoA which leads to ketone body production (can't be used for energy in RBCs (no mitochondria) or hepatocytes (no succinyl coA-acetotate coA transferase)
75
Fed state metabolism
Glycolysis and aerobic respiration
76
Fasting state metabolism
Hepatic glycogenolysis, hepatic gluconeognesis, adipose relase of FFA
77
Starvation 1-3 days metabolism
Blood glucose maintained by hepatic glycogenolysis, adipose release of FFA, muscle and liver, hepatic gluconeognesis (RBCs can't use ketones)
78
Starvation after day 3
Adipose stores (ketone bodies), protein degradation (organ failure and death)
79
Lipid transport enzymes
Pancreatic lipase (degrades TGs in small intestine) --- Lipoprotein lipase (degrades TGs circulating in chylomicrons and VLDLs - on vascular endothelial surface) --- Hepatic TG lipase (degrades TGs remaining in IDL) --- Hormone sensitive lipase (degrades TGs stored in adipocytes) --- LCAT catalyzes esterification of cholesterol
80
Apolipoprotein E
Mediates remnant uptake - all but LDL have it
81
Apolipoprotein A-I
Activates LCAT -- chylomicrons and HDL
82
Apolipoprotein C-II
Lipoprotein lipase cofactor -- chylomicrons, VLDL, HDL
83
Apolipoprotein B-48
Mediates chylomicron secretion - chylomicrons, chylomicron remnants
84
Apolipoprotein B-100
Binds LDL receptor - VLDL, IDL, LDL
85
Chylomicron
Delivers dietary TGs to peripheral tissue -- secreted by intestinal epithelial cells
86
VLDL
Delivers hepatic TGs to peripheral tissue -- secreted by liver
87
IDL
Delivers TGs and cholesterol to liver
88
LDL
Transports cholesterol from liver to tissues
89
HDL
Transports cholesterol from periphery to liver -- secreted from liver and intestine
90
Familial dyslipidemias
1-5 in alphabetical order - C, L R, T, V --- Type I (Chylomicrons - acute pancreatitis), Type II (LDL -- most common, causes accelerated atherosclerosis, tendon xanthomas, and corneal arcus), Type III (Remnants - coronary artery disease), Type IV (TGs), and Type V (VLDL)
