Term
|
Definition
absorption dependent on gut (ileum) and pancreas
malabsorption syndromes (steatorrhea) such as CF, sprue, mineral oil intake can cause deficiencies
A - vision
D - bone calcification, Ca homeostasis
E - antioxidant
K - clotting factors
toxicity more common |
|
|
Term
|
Definition
Folate - blood, neural development
Cobalamin (B12) - blood, CNS
C - ascorbic acid, antioxidant, collagen synthesis
Metabolic
B1 - thiamine: TPP
B2 - riboflavin: FAD, FMN
B3 - niacin: NAD+
B5 - pantothenic acid: CoA
B6 - pyridoxine: PLP
B12 - cobalamin
all wash out easily from body except B12 and folate (stored in liver)
B complex deficiencies often result in dermatitis, glossitis, and diarrhea |
|
|
Term
Vitamin A
Function, deficiency, excess |
|
Definition
Retinol
F: Antioxidant, constituent of visual pigments (retinal)
D: night blindness, dry skin
E: arthralgias, fatigue, HA, skin changes, sore throat, alopecia, teratogenic (cleft palate, cardiac abnormalities)
Found in liver and leafy veggies |
|
|
Term
Vitamin B1
Function, deficiency, |
|
Definition
Thiamine
F: in thiamine pyrophosphate, a cofactor for several enzymes
1. pyruvate dehydrogenase (glycolysis)
2. alpha-ketoglutarate dehydrogenase (TCA cycle)
3. transketolase (HMP shunt)
4. Branched-chain AA dehydrogenase
D: Wernicke-Korsakoff syndrome (confusion, opthalmoplegia, ataxia+memory loss, confabulation, personality change)
beriberi - dry (polyneuritis, symmetrical muscle wasting), wet (high output cardiac failure, DCM, edema)
(both W-K and BIBI neuro and cardiac manifestations)
seen in malnutrition and alcoholism (secondary to malnutrition and malabsorption) |
|
|
Term
Vitamin B2
Function, deficiency, |
|
Definition
Riboflavin
F: cofactor in oxidation and reduction (FADH2), FAD and FMN are derived from riboFlavin
D: cheilosis (inflammation of lips, scaling and fissures at corners of mouth), corneal vascularization |
|
|
Term
Vitamin B3
Function, deficiency, excess |
|
Definition
Niacin
F: constituent of NAD+, NADP+ (used in redox reactions), derived from tryptophan, synthesis requires Vit B6
D: glossitis, severe? pellagra, which can be caused by Hartnup disease (decreased tryptophan absorption), malignant carcinoid syndrome (increased tryptophan metabolism), and INH (decreased vit B6)
pellagra - diarrhea, dermatitis, dementia
E: facial flushing (due to pharm doses for treatment of hyperlipidemia) |
|
|
Term
Vitamin B5
Function, deficiency |
|
Definition
pantothenate
F: essential component of CoA (cofactor for acyl transfers) and fatty acid synthase
D: dermatitis, enteritis, alopecia, adrenal insufficiency |
|
|
Term
Vitamin B6
Function, deficiency |
|
Definition
pyridoxine
F: converted to pyridoxal phosphate, a cofactor used in transamination (ALT and AST), decarboxylation reactions, glycogen phosphorylase, and heme synthesis. Required for synthesis of niacin from tryptophan
D: convulsions, hyperirritbaility, peripheral neuropathy (deficiency inducible by INH and oral contraceptives) |
|
|
Term
Vitamin B12
Function, deficiency, excess |
|
Definition
Cobalamin
F: cofactor for homocysteine methyltransferase (transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA mutase
homocysteine + N-methyl THF --(B12)--> methionine + THF
Methylmalonyl-CoA --(B12)--> succinyl-CoA
found in animal products
synthesized only by microorganisms, very large reserve pool in liver
D: macrocytic, megaloblastic anemia; neurologic symptoms (paresthesias, subacute combined degeneration) due to abnormal myelin. prolonged? irreversible nervous system damage
usually caused by malabsorption (sprue, enteritis, Diphyllobothrium latum), lack of intrinsic factor (pernicious anemia, gastric bypass surgery) or absence of terminal ileum (Crohn's)
use of schilling test to detect etiology of deficiency |
|
|
Term
Folic Acid
Function, deficiency |
|
Definition
F: converted to tetrahydrofolate (THF), a coenzyme for 1C transfer/methylation reactions.
Important for synthesis of nitrogenous bases in DNA and RNA.
Folate from foliage, small reserve in liver
D: macrocytic, megaloblastic anemia; no neurologic symptoms (as opposed to B12 deficiency)
most common deficiency in US, can be caused by several drugs (phenytoin, sulfonamides, MTX), seen in alcoholism and pregnancy (supplemental folic acid in early pregnancy reduces NTD) |
|
|
Term
|
Definition
ATP+methionine --> SAM (methyl CH3 donor man)
SAM transfers CH3 to recipeint and becomes Homocysteine
regeneration of methionine from homocysteine (and thus SAM) depends on B12 and folate |
|
|
Term
Biotin
Function, deficiency |
|
Definition
F: cofactor for carboxylation enzymes
1. Pyruvate carboxylase: pyruvate --> oxaloacetate
2. Acetyl CoA carboxylase: acetylCoA --> malonyl CoA
3. Propionyl-CoA carboxylase: Propionyl-CoA --> methylmalonyl CoA
D: relatively rare, dermatitis, alopecia, enteritis, caused by antibiotic use or excessive ingestion of raw eggs |
|
|
Term
Vitamin C
Functions (4), deficiency |
|
Definition
ascorbic acid
F: antioxidant, facilitates iron absorption by keeping iron in reduced state which is more absorbable, necessary for hydroxylation of proline and lysine in collagen synthesis (which occurs in the ER), Necessary for dopamine B-hydroxylase, which converts dopamine to NE
D: scurvy (swollen gums, bruising, anemia, poor wound healing, perifollicular hemorrhage) |
|
|
Term
|
Definition
D2 = ergocalciferol (plants, used as pharmacological agent)
D3 = cholecalciferol (milk, sun exposure)
25-OH D3 = storage form (liver)
1,25-(OH)2 D3 (calcitriol) = active form (1 alpha hydroxylase in kidney)
F: increased intestinal absorption of Ca and PO4, increased bone resorption
D: rickets (kids, bending bones), osteomalacia (adults, soft bones), hypocalcemic tetany
E: hypercalcemia, hypocalciuria, loss of appetite, stupor
can occur in sarcoidosis (increased activation of D by epitheloid macrophages) |
|
|
Term
|
Definition
F: antioxidant (protects erythrocytes and membranes from free radical damage)
D: increased fragility of erythrocytes (hemolytic anemia), muscle weakness an neurodysfunction
Looks like B12 deficiency |
|
|
Term
|
Definition
F: catalyzes gamma carboxylation of glutamic acid residues on various proteins concerned with blood clotting, synthesized by intestinal flora
Clotting factors: II, VII, IX, X, protein C and S
D: neonatal hemorrahge with increased PT and increased aPTT but normal bleeding time (neonates have sterile intestine and are unable to synthesis vitamin K) Can also occur after prolonged use of broad-spectrum antibodies
Warfarin = vitamin K antagonist |
|
|
Term
|
Definition
F: essential for activity of 100+ enzymes. Important in formation of ZINC FINGERS (transcription factor motif)
D: delayed wound healing, hypogonadism, decreased adult hair (axillary, facial, pubic). May predispose to alcoholic cirrhosis |
|
|
Term
|
Definition
Ethanol --(alcohol dehydrogenase)--> acetaldehyde --(acetaldehyde dehydrogenase)--> acetate
NAD+ is the limiting reagent (NAD+ --> NADH)
Alcohol dehydrogenase: located in cytosol, operates via 0 order kinetics, inhibited by fomepizole
acetaldehyde dehydrogenase: located in mitochondria, inhibited by disulfiram (causing buildup of acetaldehyde with contributes to hangover symptoms) |
|
|
Term
|
Definition
1. Ethanol metabolism (requires NAD+ --> NADH)
2. Increased NADH/NAD+ ratio in liver
3. Diversion of pyruvate to lactate and OAA to malate (consumes NADH)
4a. Inhibition of gluconeogenesis --> hypoglycemia
4b. stimulation of fatty acid synthesis --> hepatic fatty change (hepatocellular steatosis) |
|
|
Term
|
Definition
protein malnutrition
causes skin lesions, edema, liver malfunction (fatty change)
small child with swollen belly
MEAL
malnutrition, edema, anemia, liver (fatty) |
|
|
Term
|
Definition
energy malnutrition
tissue and muscle wasting
loss of subcutaneous fat and variable edema |
|
|
Term
| Metabolism in the mitochondria (4) |
|
Definition
fatty acid oxidation
acetyl-CoA production
TCA cycle
oxidative phosphorylation
Heme synthesis, Urea cycle, gluconeogenesis (occurs in cytoplasm as well) |
|
|
Term
| Metabolism in the Cytoplasm (5) |
|
Definition
glycolysis
fatty acid synthesis
HMP shunt
protein synthesis (RER)
steroid synthesis (SER)
Heme synthesis, urea cycle, and gluconeogeneis (occurs in mitochondria as well) |
|
|
Term
|
Definition
| phosphofructokinase 1 (PFK1) |
|
|
Term
|
Definition
| Fructose 1,6 bisphosphatase |
|
|
Term
|
Definition
|
|
Term
| RDE of glycogen synthesis |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Glucose-6-phosphate dehydrogenase (G6PD) |
|
|
Term
| RDE of De novo pyrimidine synthesis |
|
Definition
| carbomyl phosphate synthetase II |
|
|
Term
| RDE of de novo purine synthesis |
|
Definition
| glutamine-PRPP amidotransferase |
|
|
Term
|
Definition
| carbamoyl phosphate synthetase |
|
|
Term
| RDE of fatty acid synthesis |
|
Definition
| acetyl-CoA carboxylase (ACC) |
|
|
Term
| RDE of fatty acid oxidation |
|
Definition
| carnitine acyltransferase I |
|
|
Term
|
Definition
|
|
Term
| RDE of cholesterol synthesis |
|
Definition
|
|
Term
Aerobic metabolism of glucose
ATP production |
|
Definition
32 ATP (malate-aspartate shuttle in heart and liver)
30 ATP (glycerol-3-phosphate shuttle in muscle |
|
|
Term
Anaerobic glycolysis
ATP production |
|
Definition
| 2 net ATP per glucose via substrate level phosphorylation |
|
|
Term
Activated carriers of
phosphoryl
electrons
acyl
CO2
1Carbon units
CH3 groups
aldehydes |
|
Definition
phosphoryl - ATP
Electrons - NADH, NADPH, FADH2
Acyl - coenzyme A, lipamide
CO2- biotin (cofactor for carboxylation reactions)
1C units- tetrahydrofolates
CH3 groups - SAM
Aldehydes - TPP |
|
|
Term
| Universal electron acceptors |
|
Definition
Nicotinamides and flavin nucleotides
(NAD+: generally used in catabolic processes to carry reducing equivalents away as NADH)
(NADPH - product of HMP shunt, used in anabolic processes (steroid and FA synthesis) as a supply of reducing equivalents) |
|
|
Term
|
Definition
product of HMP shunt
used in anabolic proceses, respiratory burst, and P-450 |
|
|
Term
|
Definition
phophorylates glucose to G6P in 1st step of glycolysis
ubiquitous,
high affinity (low Km),
low capacity (low Vmax),
uninduced by insulin
feedback inhibited by G6P |
|
|
Term
|
Definition
phosphorylates glucose to G6P serving as 1st step of glycolysis
Liver and B-cells
low affinity (high Km)
high capacity (high Vmax)
induced by insulin
no direct feedback
phosphorylates excess glucose (after a meal) to sequester in liver, allows liver to serves as a blood glucose buffer |
|
|
Term
Glycolysis reaction formula
(cytoplasm) |
|
Definition
| Glucose+2Pi+2ADP+2NAD+ --> 2 pyruvate + 2ATP + 2NADH + 2H+ + 2H20 |
|
|
Term
|
Definition
hexokinase/glucokinase, requires ATP
negative feedback to hexokinase via G6P |
|
|
Term
| How does Fructose6P --> Fructose 1,6 BP? |
|
Definition
phosphofructokinase-1
requires ATP
Inhibited by ATP, citrate
Enhanced by AMP, fructose 2,6BP |
|
|
Term
| What are the two substrate level phosphorylation steps of glycolysis? |
|
Definition
1,3 BPG --> 3PG (phosphoglycerate kinase)
Phosphoenolpyruvate --> pyruvate (pyruvate kinase)
inhibited by ATP, alanine
enhanced by fructose 1,6BP |
|
|
Term
| How does pyruvate --> acetyl coA |
|
Definition
pyruvate dehydrogenase
inhibited by ATP, NADH, acetyl-CoA |
|
|
Term
| How does F2,6BP regulate glycolysis/gluconeogenesis? |
|
Definition
PFK 2 is active in fed state
converts F6P to F 2,6 BP
F2,6BP is the most potent activator of PFK1 (overrides inhibition by ATP and citrate)
PFK1 acts of F6P to F1,6BP and entry to glycolysis
In fasting state, fructose bisphosphatase 2 is active, converting F2,6P back to F6P
F6P is driven towards gluconeogenesis |
|
|
Term
| Glycolytic enzyme deficiencies |
|
Definition
deficient in pyruvate kinase (95%), phosphoglucose isomerase (4%), and other glycolytic enzymes
leads to inability to maintain Na/K atpase, causing RBC (depend on glycolysis) swelling and lysis --> hemolytic anemia |
|
|
Term
| Glycolytic enzyme deficiency association |
|
Definition
hemolytic anemia
inability to maintain activity of Na/K ATPase leading to RBC swelling and lysis
RBCs metabolize glucose anaerobically (no mitochondria) and thus depend solely on glycolysis |
|
|
Term
Pyruvate dehydrogenase complex
reaction and cofactors |
|
Definition
pyruvate + NAD+ + CoA --> acetyl CoA + CO2 + NADH
cofactors:
1. pyrophosphate (B1, thiamine; TPP)
2. FAD (B2, riboflavin)
3. NAD (B3, niacin)
4. CoA (B5, pantothenate)
5. Lipoic acid (inhibited by arsenic)
complex is similar to alpha-ketoglutarate |
|
|
Term
| Activators of pyruvate dehydrogenase complex |
|
Definition
| Exercise (increases NAD+/NADH ratio, ADP, and Ca2+) |
|
|
Term
|
Definition
inhibits lipoic acid (involved in pyruvate dehydrogenase complex)
causes vomiting, rice water stools, and garlic breath |
|
|
Term
| pyruvate dehydrogenase deficiency |
|
Definition
backup of substrate (pyruvate and alanine) causes lactic acidosis, neurologic defects
can be congenital or acquired (alcoholics due to B1 deficit) |
|
|
Term
| treatment for pyruvate dehydrogenase deficiency |
|
Definition
increased intake of ketogenic nutrients
-high in fat content
-high in lysine or leucine (only purely ketogenic aa) |
|
|
Term
| Relationship of alanine and pyruvate |
|
Definition
| alanin carries amino groups (derived from breakdown of pyruvate) to the liver from muscle |
|
|
Term
| Relationship of oxaloacetate and pyruvate |
|
Definition
oxaloacetate can replenish TCA cycle or be used in gluconeogensis
Pyruvate --> oxaloacetate
enzyme = pyruvate carboxylase
consumes: Co2 and ATP |
|
|
Term
| Relationship of pyruvate and acetyl-CoA |
|
Definition
transition from glycolysis to TCA cycle
Pyruvate --> acetyl CoA
Enzyme: Pyruvate dehydrogenase
Consumes: NAD+
Produces NADH+H+ and CO2
requires: thiamine cofactor (TPP) |
|
|
Term
| Relationship of pyruvate to lactate |
|
Definition
end of anaerobic glycolysis (major pathway of RBCs, leukocytes, kidney medulla, lens, testes, and cornea)
Pyruvate --> Lactate
enzyme: LDH
consumes: NADH+H+
produces: NAD+ |
|
|
Term
|
Definition
lactate generated during anaerobic metabolism undergoes hepatic gluconeognesis --> source of glucose for muscle/RBCs
costs 4 ATP/cycle
shifts metabolic burden to the liver
Anaerobic Glycolysis (muscle/RBCs)
Glucose -- (makes 2ATP)--> 2 pyruvate --(LD)--> 2 lactate
Gluconeognesis (liver)
2 lactate --(makes 6 ATP) -->2 pyruvate --(uses 12 ATP)--> glucose |
|
|
Term
TCA cycle
substrate and product |
|
Definition
Pyruvate --> acetyl CoA (1NADH, 1Co2)
TCA cycle produces 3 NADH, 1 FADH2, 2 CO2, 1GTP (per acetyl CoA = 12 ATP/acetyl coA)
Occurs in mitochondria |
|
|
Term
| What are the 5 cofactors required by alpha-kethglutarate? |
|
Definition
B1, B2, B3, B5, lipoic acid
same ones for pyruvate dehydrogenase |
|
|
Term
|
Definition
Acetyl CoA
Citrate -> Isocitrate -> alpha-ketoglutarate -> succinyl CoA -> Succinate -> Fumarate -> malate -> oxaloacetate -> citrate
Can I keep selling sex for money, officer? |
|
|
Term
| Negative feedback for pyruvate to acetyl coA |
|
Definition
ATP, Acetyl CoA, NADH
enzyme: pyruvate dehydrogenase |
|
|
Term
| Negative feedback for acetyl CoA + oxaloacetate --> citrate |
|
Definition
ATP
enzyme: Citrate synthase |
|
|
Term
| Feedback for isocitrate --> alpha ketoglutarate |
|
Definition
Negative: ATP, NADH
Positive: ADP
enzyme: isocitrate dehydrogenase
produces: CO2 and NADH |
|
|
Term
| Feedback to alpha-ketoglutarate --> succinyl CoA |
|
Definition
Negative: succinyl CoA, NADH, ATP
Cofactor: CoA-SH
Enzyme: alpha-KG dehydrogenase |
|
|
Term
| Reactions of TCA cycle producing NADH |
|
Definition
Isocitrate --> alpha ketoglutarate (CO2 also made)
alpha-KG --> succinyl Co A (CO2 also made)
Malate --> Oxaloacetate |
|
|
Term
| Reaction of TCA cycle producing FADH2 |
|
Definition
|
|
Term
| Reaction of TCA cycle producing GTP |
|
Definition
Succinyl-CoA --> succinate
produces GTP and CoA |
|
|
Term
| Mechanism for NADH electron entry to mitochondria |
|
Definition
malate-aspartate shuttle (NADH)
glycerol-3-phosphate shuttle (NADH) |
|
|
Term
| Electron transfer sites (ATPs made) for NADH and FADH2 |
|
Definition
Complex I (NADH) - 3 ATP
Complex II (FADH2) - 2ATP, lower energy than NADH
passage of electrons --> formation of proton gradient --> coupled to oxidative phosphorylation --> ATP production |
|
|
Term
| Electron transport inhibitors |
|
Definition
directly inhibit electron transport, decreased proton gradient, block ATP synthesis
Rotenone, CN-, antimycin A, CO |
|
|
Term
|
Definition
| Electron transport inhibitor |
|
|
Term
|
Definition
| Electron transport inhibitor |
|
|
Term
|
Definition
| Electron transport inhibitor |
|
|
Term
|
Definition
| Electron transport inhibitor |
|
|
Term
|
Definition
directly inhibit mitochondrial ATPase, causing an increased proton gradient
No ATP production because e transport stops
oligomycin |
|
|
Term
|
Definition
|
|
Term
|
Definition
increase permeability of membrane, causing a decreased proton gradient and increased oxygen consumption.
ATP synthesis stops, but e transport continues
2,4-DNP, aspirin, thermogenin in brown fat |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Irreversible enzymes of gluconeogenesis |
|
Definition
Pyruvate carboxylase (mitochondria)
PEP carboxykinase (cytosol)
Fructose 1,6 bisphosphatase (cytosol)
Glucose 6 phosphatase (ER)
pathway produces fresh glucose |
|
|
Term
|
Definition
| liver (kidney and intestinal epithelium to lesser extent) |
|
|
Term
|
Definition
Mitochondria
Pyruvate --> oxaloacetate
requires biotin, ATP
Activated by acetyl-CoA |
|
|
Term
|
Definition
cytosol
Oxaloacetate --> phosphoenolpyruvate
requires GTP |
|
|
Term
| Fructose 1,6 - bisphosphatase |
|
Definition
cytosol
Fructose 1,6 bisphosphate --> fructose 6P |
|
|
Term
|
Definition
|
|
Term
| Deficiency of key gluconeogenic enzymes |
|
Definition
| causes hypoglycemia (muscle cannot participate in gluconeogenesis) |
|
|
Term
| Gluconeogenesis and fatty acids |
|
Definition
odd chain - yield 1 propionyl-CoA, able to enter TCA cycle, undergo gluconeogenesis and serve as glucose source
Even chain - yield acetyl CoA equivalents, cannot produce new glucose |
|
|
Term
|
Definition
pentose phosphate pathway
produces NADPH (required for FA and steroid biosynthesis, glutathione reduction inside RBCs)
2 phases: oxidative and nonoxidative
occurs in cytoplasm
No ATP used or produced |
|
|
Term
| HMP shunt product and uses |
|
Definition
pentose phosphate pathway
NADPH
required for FA and steroid biosynthesis and glutathione reduction inside RBCs |
|
|
Term
| Anatomical sites of HMP shunt |
|
Definition
| lactating mammary glands, liver, adrenal cortex, (all sites of FA and steroid synthesis), RBCs |
|
|
Term
| Oxidative reaction of HMP shunt |
|
Definition
irreversible
RDE: G6P dehydrogenase
Product: NADPH (later used in FA and steroid synthesis, glutathione reduction, and cytochrome P450) |
|
|
Term
| Nonoxidative reaction of HMP shunt |
|
Definition
reversible
Key enzyme: Transketolases (needs thiamine)
Prodcut: ribose-5P (for nt synthesis); G3P, F6P (glycolytic intermediates) |
|
|
Term
| Extracellular reactions of respiratory burst |
|
Definition
1. membrane bound NADPH oxidase (02 --> O2e)
2. Superoxide dismutase (O2e --> H2O2)
3. Myeloperoxidase (H2O2+ Cl --> HOCLe)
HOCLe = bleach (hypochlorite) |
|
|
Term
|
Definition
membrane bound
in nuetrophils and macrophages
activated in respiratory burst |
|
|
Term
| Intracellular reactions of respiratory burst |
|
Definition
(EC = NADPH oxidase, SOD, myeloperoxidase)
IC: H2O2 brought intracellular
4. Catalase/glutathione peroxidase (H2O2+GSH --> H20+GSSG)
5. Glutathione reductase (NADPH+GSSG --> NAD+ + GSH)
6. G6P dehydrogenase (NADP+ + G6P --> NADPH+6PG)
GSH/GSSG = reduced glutathione/oxidized glutathione |
|
|
Term
|
Definition
chronic granulomatous disease
(inability to create HOCle for bacteria killing) |
|
|
Term
| Glucose 6P dehydrogenase deficiency: clinical finding |
|
Definition
causes hemolytic anemia
G6P dehydrogenase normally generates NADPH (G6P+NADP+ --> 6PG+NADPH)
NADPH is used to reduce glutathione
which is then used to detox free radicals and peroxides
decreased NADPH in RBCs = poor RBC defense against oxidizing agents |
|
|
Term
| exogenous oxidizing agents |
|
Definition
| fava beans, sulfonamides, primaquine, antiTB drugs |
|
|
Term
| G6P dehydrogenase deficiency: inheritance and associations |
|
Definition
| X linked Recessive, most common human enzyme deficiency, more prevalent among blacks, increased malarial resistance, heinz bodies, bite cells |
|
|
Term
|
Definition
altered Hemeglobin precipitated within RBCs
phagocytosis = Bite bodies
seen in G6P dehydrogenase deficiency |
|
|
Term
|
Definition
result form phagocytic removal of Heinz bodies by macs
seen in G6P dehydrogenase deficiency |
|
|
Term
| Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting |
|
Definition
|
|
Term
| Treatment of fructose intolerance |
|
Definition
| decreased intake of both fructose and sucrose (glucose+fructose) |
|
|
Term
| Fructose intolerance inheritance |
|
Definition
deficiency of aldolase B
AR |
|
|
Term
| Fructose intolerance mechanism |
|
Definition
Deficiency of aldolase B
Fructose1P accumulates
decreases available phosphate
causes inhibition of glycogenolysis and gluconeogenesis |
|
|
Term
| Symptoms: fuctose appears in blood and urine |
|
Definition
|
|
Term
| Essential fructosuria inheritance |
|
Definition
|
|
Term
| Essential fructosuria outcome |
|
Definition
benign, asymptomatic condition because fructose does not enter cells
disorders of fructose metabolism cause milder symptoms than analagous disorders of galactose metabolism |
|
|
Term
|
Definition
1. Fructokinase (fructose+ATP --> F1P+ADP)
2.Aldolase B (F1P --> dihydroxyacetoneP and glyceraldehyde)
eventually to G3P --> glycolysis
see first aid 106 |
|
|
Term
| Symptoms: failure to thrive, jaundice, hepatomegaly, infantile cataracts, MR |
|
Definition
|
|
Term
| Classic galactosemia inheritance |
|
Definition
Absence of galactose-1P uridyltransferase
AR |
|
|
Term
| Classic galactosemia mechanism |
|
Definition
absence of galactose1P uridyltransferase (enzyme normally facilitates Galactose1P --> Glucose1P)
damage is caused by accumulation of toxic substances (galactitol accumulates in the eye) |
|
|
Term
| Treatment of classic galactosemia |
|
Definition
| exclude galactose and lactose (galactose+glucose) from diet |
|
|
Term
| Galactokinase deficiency inheritance |
|
Definition
|
|
Term
| Symptoms: galactose appears in blood and urine, failure to track objects or to develop social smile |
|
Definition
Galactokinase deficiency
Vision problems due to infantile cataracts |
|
|
Term
| Galactokinase deficiency mechanism |
|
Definition
Galactokinse works on Galactose --> Galactose 1P
deficiency leads to accumulation of galacitol (promoted by aldose reductase)
relatively mild |
|
|
Term
|
Definition
see first aid 107
1a. aldose reductase (galactose --> galacitol)
1b. Galactokinase (galactose --> galactose 1p) uses ATP
2. Uridyl transferase (Galactose 1P --> glucose 1P)
glucose1P --> glycolsis |
|
|
Term
| Symptoms: bloating, cramps, osmotic diarrhea |
|
Definition
|
|
Term
| Treatment of Lactase deficiency |
|
Definition
avoid dairy
add lactase pills to diet |
|
|
Term
| Lactase deficiency mechanims |
|
Definition
age-dependent and/or hereditary lactose intolerance
blacks, Asians
due to los of brush border enzymes |
|
|
Term
| Amino acids found in proteins |
|
Definition
|
|
Term
|
Definition
Glucogenic: Met, Val, Arg, His
Glucogenic/ketogenic: Ile, Phe, Thr (threonine), Trp (tryptophan)
Ketogenic: Leu, Lys |
|
|
Term
|
Definition
| Asp and Glu (negatively charged at body pH) |
|
|
Term
|
Definition
Arg (most basic)
His (no charge at body pH)
Lys |
|
|
Term
| Amino acids required during periods of growth |
|
Definition
|
|
Term
| Amino acids increased in histones |
|
Definition
| Arg and Lys (both basic, bind negatively charged DNA) |
|
|
Term
|
Definition
draw cycle (p108)
Ornithine --(carbamoyl phosphate)--> citruline, --(aspartate)--> argininosuccinate -->(fumarate) + arginine --> (Urea) + ornithine
Ordinarily, careless crappers are also frivolous about urination |
|
|
Term
|
Definition
| carbamoyl phosphate synthetase I |
|
|
Term
| Catabolism of amino acid (products) |
|
Definition
pyruvate, acetyl CoA
NH4+ (converted to urea and excreted by kidneys) |
|
|
Term
|
Definition
NH2-C0-NH2
NH2 (from NH4)
C=O (from CO2)
NH2 (from aspartate) |
|
|
Term
| Transport of ammonium in muscle |
|
Definition
NH3 from amino acids is taken by alpha-ketoglutarate
amino acids (NH3) + alpha-ketoglutarate --> alpha ketoacids + glutamate (NH3)
pyruvate takes the NH3 from glutamate to generate alanine (NH3)
Glutamate (NH3)+pyruvate --> alpha-ketoglutarate + alanine (NH3)
Alanine is transferred to the liver |
|
|
Term
| Transport of ammonium in the liver |
|
Definition
Alanine (NH3) from muscle transfers NH3 to alphaketoglutarate, making glutamate (NH3)
NH3 enters the urea cycle and is made into urea |
|
|
Term
|
Definition
| ammonia intoxication - tremor, slurring of speech, somnolences, vomiting, cerebral edema, blurring of vision |
|
|
Term
| Hyperammonemia pathogenesis |
|
Definition
acquired (liver disease) or hereditary (urea cycle enzyme deficiencies)
results in excess NH4+, which depletes alpha-ketoglutarate, leading to inhibition of TCA cycle |
|
|
Term
| Treatment of hyperammonemia |
|
Definition
| benzoate or phenylbutyrate to lower serum ammonia levels |
|
|
Term
| Ornithine transcarbamoylase deficiency pathogenesis |
|
Definition
conversion of ornithine+carbamoyl phosphate to citruline is interrupted, can't eliminate ammonia
excess carbamoyl phosphate synthetase I is converted to orotic acid |
|
|
Term
| Ornithine trancarbamoylase deficiency findings |
|
Definition
| orotic acid in blood and urine, decreased BUN, symptomse of hyperammonemia (somnolence, vomiting, tremor, slurring of speech, cerebral edema, blurring of vision) |
|
|
Term
| Ornithine transcarbamoylase deficiency inheritance |
|
Definition
most common urea cycle disorder
X-linked recessive (vs. other urea cycle enzyme deficiencies which are AR) |
|
|
Term
| Derivatives of phenylalanine |
|
Definition
tyrosine --> Thyroxine and Dopa
Dopa--> melanin and dopamine
Dopamine --> NE
NE --> Epi |
|
|
Term
| Derivatives of tryptophan |
|
Definition
Tryptophan --> Niacin --> NAD+/NADP+
Tryptophan--> serotonin --> melatonin |
|
|
Term
|
Definition
|
|
Term
|
Definition
| glycine --> porphyrin --> heme |
|
|
Term
|
Definition
arginine -->
1. creatinine
2. Urea (and ornithine)
2. Nitric Oxide |
|
|
Term
|
Definition
1. GABA (glutamate decarboxylase, requires B6)
2. Glutathione |
|
|
Term
| Phenylketonuria pathogenesis |
|
Definition
unable to convert Phenylalanine to tyrosine due to either
1. decreased phenylalanine hydroxylase 2. decreased tetrahydrobiopterin cofactor
This makes tyrosine an essential amino acid
Intake of phenylalanine leads to excess phenylketones |
|
|
Term
|
Definition
See FA 109
Phenylalanine+THB --> tyrosine+ DHB (phenylalanine hydroxylase)
DHB+NADPH --> THB+NADP+ (dihydropterin reductase) |
|
|
Term
| Findings of phenylketonuria |
|
Definition
| MR, growth retardation, seizures, fair skin, eczema, MUSTY body odor (disorder of aromatic amino acid metabolism) |
|
|
Term
|
Definition
| phenylketnouria (disorder of aromatic amino acid metabolism) |
|
|
Term
|
Definition
| decrease phenylalanine (contained in aspartame) and increase tyrosine in diet |
|
|
Term
|
Definition
| phenylacetate, phenyllactate, phenylpyruvate |
|
|
Term
|
Definition
| lack of proper dietary therapy during pregnancy. Infant: microcephaly, MR, growth retardation, congenital heart defects |
|
|
Term
|
Definition
AR
1:10,000
screened for 2-3 d after birth |
|
|
Term
| Alakaptonuria (ochronosis) pathogenesis |
|
Definition
| congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine, benign |
|
|
Term
| Inheritance of alkaptonuria |
|
Definition
|
|
Term
|
Definition
| dark CT, pigmented sclera, urine and ear wax turns black on standing, debilitating arthralgias (sometimes) |
|
|
Term
|
Definition
Congenital deficiency of either:
1. tyrosinase (inability to synthesize melanin from tyrosine) - AR
2. defective tyrosine transporters (decreased amounts of tyrosine and thus melanin)
3. can result from lack of migration of neural crest cells |
|
|
Term
|
Definition
| Lack of melanin = increased risk of skin cancer |
|
|
Term
|
Definition
| variable due to locus heterogeneity |
|
|
Term
| Ocular albinism inheritance |
|
Definition
|
|
Term
| Homocystinuria inheritance and causes |
|
Definition
all 3 AR, cystine becomes essential
1. cystathionine synthase deficiency
2. decreased affinity of cystathionine synthase for pyridoxal phosphate
3. homocysteine methyltransferase deficiency |
|
|
Term
|
Definition
FA 110
Methionine -1-> homocysteine -2-> cystathionine -3-> cysteine
1. homocysteine methyltransferase (forward via SAM, revers via THF and B12)
2. Cystathionine synthetase, B6 |
|
|
Term
|
Definition
| increased homocysteine in urine, MR, osteoporosis, tall stature, kyphosis, lens subluxation (down and in) and atherosclerosis (stroke, MI) |
|
|
Term
| Disease caused by cystathionine synthase deficiency and treatment |
|
Definition
homocystinuria
Tx: decrease Met, increase Cys, increase B12 and folate
This treatment will cause reaction to move towards generation of methionine, decreasing homocysteine levels |
|
|
Term
| disease caused by decreased affinity of cystathionine synthase for pyridoxal phosphate and treatment |
|
Definition
Homocystinuria
Tx: increase B6, overcome decreased affinity |
|
|
Term
|
Definition
| hereditary defect of renal tubular amino acid transporter for cysteine, ornithine, lysine and arginine in the PCT of the kidneys |
|
|
Term
| Cystinuria clinical findings |
|
Definition
| excess cystine in urine leading to precipitaiton of cystine kidney stones (cystine staghorn calculi) |
|
|
Term
| Inheritance of cystinuria |
|
Definition
|
|
Term
|
Definition
| acetazolamide to alkalinize the urine |
|
|
Term
|
Definition
| 2 cysteines connected by disulfide bond |
|
|
Term
| Maple syrup urine disease cause |
|
Definition
decreased alpha-ketoacid dehydrogenase causes blocked degradation of branched amino acids (Ile, Leu, Val)
leads to increased alpha ketoacids in blood (especially Leu)
I Love Vermont maple syrup from maple tees with branches |
|
|
Term
| Clinical findings of maple syrup urine disease |
|
Definition
Severe CNS defects, MR, death
urine smells like maple syrup |
|
|
Term
| adenosine deaminase deficiency |
|
Definition
pruine salvage deficiency
excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase --> prevents DNA synthesis and thus decreased lymphocyte count
major cause of SCID |
|
|
Term
|
Definition
adenosine deaminase deficiency
Severe combined immunodeficiency disease, affects kids |
|
|
Term
|
Definition
purine salvage deficiency
defective purine salvage owing to absence of HGPRT, which converts hypoxanthine to IMP and guanine to GMP. Results in excess uric acid production. |
|
|
Term
| Clinical findings of Lesch Nyhan syndrome |
|
Definition
| MR, self-mutilation, aggression, hyperuricemia, gout, choreathetosis |
|
|
Term
| inheritance of Lesch-Nyhan syndrome |
|
Definition
X-linked recessive
absent HGPRT (he's got purine recovery trouble) |
|
|
Term
|
Definition
|
|
Term
|
Definition
inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) due to defect in either
1. orotic acid phosphoribosyltransferase
2. orotidine 5'phosphate decarboxylase |
|
|
Term
| Inheritance of orotic aciduria |
|
Definition
|
|
Term
| Clinical findings of orotic aciduria |
|
Definition
| increased orotic acid in urine, megaloblastic anemia (does not improve with administration of B12 or folic acid), failure to thrive, no hyperammonemia (vs. OTC deficiency which would have increased orotic acid with hyperammonemia) |
|
|
Term
| Treatment of orotic aciduria |
|
Definition
| oral uridine administration |
|
|
Term
|
Definition
B-cells of pancreas in response to ATP from glucose metabolism acting on K channels and depolarizing cells
required for adipose and muscle uptake of glucose |
|
|
Term
| Sites that don't require insulin for glucose uptake |
|
Definition
Brain
RBCS
Intestine
Cornea
Kidney
Liver |
|
|
Term
|
Definition
found in RBCS and brain
don't require insluin |
|
|
Term
|
Definition
| round in B islet cells, liver, kidney |
|
|
Term
|
Definition
found in adipose, skeletal, muscle
require insulin |
|
|
Term
| regulators of glycogen synthase |
|
Definition
+ insulin, glucose (muscle - insulin only)
- glucagon, epinepherine (muscle - epi only)
Insulin dephosphorylates (GS-P to GS) (decreased cAMP --> decreases PKA)
glucagon phosphorylates (increases cAMP --> increasing PKA) |
|
|
Term
| regulators of Glycogen phosphorylase |
|
Definition
Liver
+ epi, glucagon
- insulin
Muscle
+ AMP, Epi
- ATP, insulin |
|
|
Term
|
Definition
branches have a(1,6) bonds
linkages have a(1,4) bonds |
|
|
Term
| Glycogen metabolism in muscle |
|
Definition
| glycogen undergoes glycogenolysis to form glucose, which is rapidly metabolized during exercise |
|
|
Term
|
Definition
| glycogen is stored and undergoes glycogenolysis to maintain blood sugar at appropriate levels |
|
|
Term
| Steps of G6P to Limit dextran |
|
Definition
G6P --> G1P -1->UDP glucose -2->storage form of glycogen -3-> branched glycogen -4-> limit dextran
1. UDP-glucose pyrophosphorylase
2. Glycogen synthase
3. Branching enzyme
4. glycogen phophorylase
limit dextran = (4 glucose residues in branched configuration) |
|
|
Term
| Glycogenolysis/glycogen synthesis |
|
Definition
FA 113
Overview
G6P --> glycogen
Glycogen --> G1P and limit dextran
Limit dextran --> glucose |
|
|
Term
| Role of lysosomal alpha-1,4-glucosidase (II) |
|
Definition
| degrades small amount of glycogen to glucose+Pi |
|
|
Term
|
Definition
| Generate Limit dextran and G1P |
|
|
Term
|
Definition
| degrades Limit dextran to glucose |
|
|
Term
| Glucose 6 phosphatase (I) |
|
Definition
|
|
Term
| Glycogen storage diseases |
|
Definition
12 types, abnormal glycogen metabolism and accumulation of glycogen within cells
Von Gierkes, Pompes, Coris, McArdles
Very Poor Carbohydrate Metabolism |
|
|
Term
Von Gierke's disease
deficient enzyme |
|
Definition
Glycogen storage disease Type I
Glucose 6 phosphatase
no gluconeogenesis or glycogenolysis |
|
|
Term
| Findings: severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, hepatomegaly |
|
Definition
Von Gierke's disease (type I)
Enzyme: Glucose 6 phosphate |
|
|
Term
|
Definition
Glycogen storage disease Type II
Lysosomal a-1,4-glucosidase (acid maltase) |
|
|
Term
| Findings: cardiomegaly and systemic findings leading to early death |
|
Definition
Pompe's disease (II)
enzyme: lysosomal a1,4 glucosidase
pompe's trashes the pump (heart, liver, muscle) |
|
|
Term
|
Definition
Glycogen storage disease Type III
Debranching enzyme (a1,6 glucosidase)
milder form of Type I |
|
|
Term
| Findings: mild fasting hypoglycemia and increased glycogen in liver, normal blood lactate levels |
|
Definition
Cori's disease (III)
enzyme: debranchin enzyme a1,6 glucosidase
gluconeogenesis is intact |
|
|
Term
|
Definition
glycogen storage disease Type V
Enzyme: skeletal muscle glycogen phosphorylase |
|
|
Term
| Findings: increased glycogen in muscle, painful muscle cramps, myoglobinuria with strenuous exercise |
|
Definition
McArdle's disease (V)
enzyme: skeletal muscle glycogen phosphorylase
can't break down glycogen in muscle |
|
|
Term
| Deficiency: glucose 6 phosphatase |
|
Definition
|
|
Term
| Deficiency: lysosomal a-1,4 glucosidase |
|
Definition
|
|
Term
| Deficiency: debranching enzyme (a1,6 glucosidase) |
|
Definition
|
|
Term
| Deficiency: skeletal muscle phosphorylase |
|
Definition
|
|
Term
|
Definition
Lysosomal storage disease
sphingolipidoses
enzyme: alpha-galactosidase A
accumulated substrate: ceramide trihexoside
XR |
|
|
Term
|
Definition
Lysosomal storage disease
sphingolipidoses
enzyme: B glucocerebrosidase
accumulated substrate: glucocerbroside
AR (most common) |
|
|
Term
|
Definition
Lysosomal storage disease
sphingolipidoses
enzyme: sphinomyelinase
accumulated substrate: sphinomyelin
AR |
|
|
Term
|
Definition
Lysosomal storage disease
sphingolipidoses
enzyme: Hexosaminidase A
accumulated substrate: GM2 ganglioside
AR |
|
|
Term
|
Definition
Lysosomal storage disease
sphingolipidoses
enzyme: Galactocerebrosidase
accumulated substrate: Galactocerbroside
AR |
|
|
Term
| Metachromatic leukodystrophy |
|
Definition
Lysosomal storage disease
sphingolipidoses
enzyme: Arylsulfatase A
accumulated substrate: Cerebroside sulfate
AR |
|
|
Term
| Findings: Peripheral neuropathy of hands/feet, angiokeratomas, CV/renal disease |
|
Definition
Fabry's disease
Lysosomal storage disease
sphingolipidoses
enzyme: alpha-galactosidase A
accumulated substrate: ceramide trihexoside
XR |
|
|
Term
| Findings: Hepatosplenomegaly, aseptic necrosis of femur, bone crises, macrophages that look like crumpled tissue paper |
|
Definition
Gaucher's disease
Lysosomal storage disease
sphingolipidoses
enzyme: B glucocerebrosidase
accumulated substrate: glucocerbroside
AR (most common) |
|
|
Term
| Findings: progressive neurodegeneration, hepatosplenomegaly, cherry red spot on macula, foam cells |
|
Definition
Neimann Pick disease
Lysosomal storage disease
sphingolipidoses
enzyme: sphinomyelinase
accumulated substrate: sphinomyelin
AR |
|
|
Term
| Findings: peripheral neuropathy, developmental delay, cherry-red spot on macula, lysosomes with onion skin |
|
Definition
Tay-Sachs disease
Lysosomal storage disease
sphingolipidoses
enzyme: Hexosaminidase A
accumulated substrate: GM2 ganglioside
AR |
|
|
Term
| Findings: Peripheral neuropathy, developmental delay, optic atrophy, globoid cells |
|
Definition
Krabbe's disease
Lysosomal storage disease
sphingolipidoses
enzyme: Galactocerebrosidase
accumulated substrate: Galactocerbroside
AR |
|
|
Term
| Findings: central and peripheral demyelination with ataxia, dementia |
|
Definition
Metachromatic leukodystrophy
Lysosomal storage disease
sphingolipidoses
enzyme: Arylsulfatase A
accumulated substrate: Cerebroside sulfate
AR |
|
|
Term
| Findings: central and peripheral demyelination with ataxia, dementia |
|
Definition
Metachromatic leukodystrophy
Lysosomal storage disease
sphingolipidoses
enzyme: Arylsulfatase A
accumulated substrate: Cerebroside sulfate
AR |
|
|
Term
|
Definition
Lysosomal storage disease
Mucopolysaccharidoses
enzyme: a-L-iduronidase
accumulated substrate: Heparan sulfate, dermatan sulfate
AR |
|
|
Term
| Findings: developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly |
|
Definition
Hurler's syndrome
Lysosomal storage disease
Mucopolysaccharidoses
enzyme: a-L-iduronidase
accumulated substrate: Heparan sulfate, dermatan sulfate
AR |
|
|
Term
|
Definition
Lysosomal storage disease
Mucopolysaccharidoses
enzyme: iduronate sulfatase
accumulated substrate: heparan sulfate, dermatan sulfate
XR |
|
|
Term
| Findings: mild developmental delay, no corneal clouding, mild hepatosplenomegaly, aggressive behavior, mild airway obstruction, mild gargoylism |
|
Definition
Hunter's syndrome
Lysosomal storage disease
Mucopolysaccharidoses
enzyme: iduronate sulfatase
accumulated substrate: heparan sulfate, dermatan sulfate
XR |
|
|
Term
| Which lysosomal storage diseases have increased incidence in Ashenazi Jews? |
|
Definition
| Tay-Sachs, Niemann Pick, Gauchers |
|
|
Term
| How are fatty acids synthesized? |
|
Definition
Acetyl CoA is exported from mitochondrial matrix by the citrate shuttle in the inner mitochondrial membrane
in the cell cytoplasm: acetyl CoA combines with CO2 (cofactor biotin for carboxylation) to form malonyl-CoA which enters fatty acid synthesis |
|
|
Term
|
Definition
Fatty acid + CoA is broken down to acyl CoA by fatty acid CoA synthetase
Acyl CoA is transported by the carnitine shuttle in the inner mitochondrial membrane into the mitochondrial matrix (shuttle is inhibited by malonyl coA)
Acyl CoA undergoes B-oxidation (breakdown to acetyl CoA groups)
Acetyl CoA groups can become Ketone bodies or enter the TCA cycle |
|
|
Term
|
Definition
| inability to use LCFAs and toxic accumulation |
|
|
Term
| Where does FA degradation occur? |
|
Definition
| in the mitochondria, where the products will be consumed |
|
|
Term
| Acyl CoA dehydrogenase deficiency |
|
Definition
increased dicarboxylic acids
decreased glucose and ketones |
|
|
Term
|
Definition
acetoacetate and B-hydroxybutyrate
from metabolism of fatty acids and amino acids in the liver
used in muscle and brain |
|
|
Term
| What happens in prolonged starvation and DKA? |
|
Definition
oxaloacetate is depleted for gluconeogenesis
stalls the TCA cycle
Glucose and FFA shunted toward ketone body production |
|
|
Term
| Why are ketones produced in alcoholism? |
|
Definition
Excess NADH shunts oxaloacetate to malate
stalls the TCA cycle
Glucose and FFA shunted toward ketone body production |
|
|
Term
| What are ketone bodies made from? metabolized to? |
|
Definition
HMG-CoA
metabolized by brain to 2 molecules of acetyl CoA
excreted in urine |
|
|
Term
| What would a urine test to ketone bodies show? |
|
Definition
presence of ketones but
No B-hydroxybutyrate (favored by high redox state) |
|
|
