HB1- exam 2 note cards grabbag.txt

steriod ring system, an important part of membrane integrity, provides carbon platform with messages above and below rings (methyl or hydroxyl groups)

After absorption in the gut, transported to liver and tissues via chylomicrons

cholesterol is broken down into bile salts by hydroxylases, excreted form of cholesterol

return to the liver after reabsorption in the terminal ileum, recycled form of cholesterol

humans can synthesize up to 1g cholesterol per day

most cholesterol is stored as esters because you can store fatty acids on them, transported via lipoprotein

water soluble, fat glob, apolipoproteins on surface allow for cell recogniton, cholesterol ester, free fatty acids, triglycerides in the core

18 moles of aceytl CoA, 36 moles of ATP, 16 moles of NADPH

cytoplasm of hepatic liver cells, starts wth acetyl CoA

Acetyl CoA (2C)--(HMG CoA reductase)-->mevalonate (6C)--->farnesyl pyrophosphate( 15 C)---> combine 2 farnesyl--->squalene (30C)--->7-dehydro-cholesterol

HMG CoA reductase-->takes ester and reduces it down to an alcohol (mevalonate) **IRREVERSIBLE

Phosphorylated is inactive and non-phosphorylated is active

Hepatic HMG CoA reductase synthetase--> stimulated by well fed state, inhibited by dietary cholesterol intake

inhibit HMG-CoA reductase to prevent cholesterol biosynthesis-->lower intracellular cholesterol and lowers apo B/E recpetor

turns cholecterol in cholesterol ester

Oxysterols (hydroxylated cholexterol) bind to Liver X receptor (LXR)-->upregulates SREBPs-->SCAP bring SREBP to protease-->cleaved by protease-->activates SREBP in gene expression

de novo biosynthesis, Hydrolysis of cholesterol esters (cleave esters), Dietary intake of cholesterol and uptake from chylomicrons, receptor mediated uptake of cholesterol containing lipoproteins (LDL)

Inhibition of cholesterol biosynthesis, Downregulate the LDL receptor, Esterification of cholesterol by acyl-CoA, Release of cholesterol to HDL, Conversion of cholesterol to bile salts or steroid hormones

insulin and tri-iodo-->increases cholesterol biosynthesis, glucagon and cortisol-->decrease cholesterol biosynthesis

C21 corticoids in adrenal cortex, C19 androgens in testis, C18 estrogens in ovary

penetrate plasma membrane, bind to cytoplasmic locasted receptors-->causes conformational change in transcription factors

can't cross plasma membrane->bind to cell surface receptor-->termed first messengers-->intracellualr effects are mediated by small molecules like cAMP

vasodilator used for angina, nitro pakcets are nitrated glycerol molecules-->signal the relaxation of smooth muscle in blood vessels by stimulation of guanylate cyclase= changes in intracelluar Ca2+

cleaves specific phospholipis to generate lipids messengers (arachidonic acid, DAG)

C20 unsaturdated fatty acid-->lipid 2nd messenger or inflammatory messenger

synthesized in membranes from AA, signal via G-protein receptors, made via COX1 and COX2 enzymes

Made from AA via lipoxygenases, have roles in inflammation

cleaves DAG or phospholipid-->arachodonic acid

use arachodonic acid make prostaglandins thromboxane, prostacyclin

use arachodonic acid make leukotrienes

use arachodonic acid make HETE (CO/NO inhibit here)

start with AA --> make PGG2--> use peroxidase to make PGH2

vasoconstrictors

Vasodilators

Fever inducers (COX1 and COX2 convert AA to PGG2)

non selective COX inhibitors (aspiring, ibuprofen), block COX1 and COX2-->inhibits the synthesis of PGG2 from AA)

irreversibly acetylates COX1 and COX2, reduces inflammation, blocks the production of thromboxane (vasoconstrictor and clot builder)

Steroidal anti-inflammatory drugs, inhibit PLA2, block all eicosanoids from converting DAG and phospholipids---> Arachodonic acid

type of eicosanoid not made form COX1 and COX2, inflammatory/vasoactive mediators, made from AA via the action of lipoxygenases (which add O to lipid chains)

40% of myeloproliferative disorders-->reduced lipoxygenases activity and increased synthesis of thromboxane

AA uses 5-LO and FLAP to make HPETE--> becomes LTA4 uses enzyme LTA4 hydrolase--> LTB4 (power attractant for immune cells)

power attractant for immune cells, involved in ashmatic and allergic reactions

blood glucose levels low-->glucagon is released-->leads to the degradation of glycogen--> and gluconeogenesis--.synthesize glucose from small molecules

on liver and recetpros

increases glucose uptake and storage-->decreases cAMP-->dephosphorylates-->increase glycogen synthesis,fatty acid synthesis, decreasse gluconeogenesis

increase in cAMP-->activates PKA-->phosphorylates-->increase glood glucose, gluconeogenesis

occurs in the cytoplasm

sole source of ATP for RBC, total glucose oxidation supplies almost all the ATP for brain (fatty acids can't cross BBB)

supplies almost all the ATP under aerobic conditions

function depends on nutritional and hormonal state (well fed vs. fasting state)

GLUT1 in Brain and RBC, GLUT2 in intesinal epithelial, liver, GLUT4 in muscle and adipose tissue

first step in converting glucose-->gluc 6-P, high Km, low affinity for glucose, never saturated, can always take up glucose

first step in converting glucose-->gluc 6-P, low Km, high affinity for glucose, saturated all times

PEP and 1,3-BP have high energy bond that can drive the synthesis of ATP (only other molecule that does this is creatine phosphate)

Glucose+ 2NAD+ + 2ADP + 2Pi--->2 pyruvate + 2 NADH + 2 ATP

Glucose + 2ADP + 2 Pi --> 2 lactate + 2 ATP

Niacin

Riboflavin

Thiamine

B5 Pantothenic acid

Powerful odizing agent: NADPH Oxidase, superoxide dismutase, myeloperoxidase

O2-, H2O2, HOCl

most important enzyme in pentose phosphate pathway, primary regulation step,causes hemolytic anemia due to inability to detoxift oxidizing enzyme (in pentose phosphate)

deficiency is hypoxanthin-guanine phosphoribosyl transferase (HGPRT)-->overaccumulation of PRPP (substrate for step 2 in purine biosynthesis), X-linked disorder

Hexokinase, Glucokinase, PFK-1,PK

liver

overnight fasting begin gluconeogenesis

The first 2-3 h after birth, newborn uses gluconeogensis

first intermediate in gluconeogenesis is oxaloacetate-->translocated to cytosol as malata where NAD+ is needed to regenerate oxaloacetate-->large amt of alcohol reduces NAD+

enters at DHAP

enters at pyruvate

in mitochondira, turns Pyruvate-->oxaloacetate, needs ATP + Biotin as CO2 carrier

glucogenic AAs, Lactate, Glycerol

from degradation of skeletal muscle protein--only 2 of 20 cant be used for glucose synthesis--can enter back in as pyruvate or other places in TCA cycle

leucine and lysine

from anaaerobic muscle of RBC-->LDH convers lactate to pyruvate-->goes into gluconeogenesis

3C compound from adipose tissue to liver-->to be converted back to glycerl-3P-->oxidation to DHAP-->goes into gluconeogenesis

Lactate cycle to take lactate back to the liver to convert them back to glucose--uses enzyme LDH

Takes alanine back to the liver to convert it back to glucose--uses enzyme alanine transaminase

the energy storage polysaccharide in animals

liver and skeletal muscle

glycogenin

glycogen synthesis

glycogen breakdown (epinephrine triggers cAMP, epnephrine is important in muscle)

epinephrine (muscle doesn't have glucagon receptors)

60,000 (in liver there are more)

polysaccharide core alpha 1,4 and alpha1,6 bonds, protein coat has all the enzymes to synthesize, degrade and regulate glycogen

the core protein at the center of glycogen core, only reducind end, everything else is non reducing

significant for break down, the more branch points you have the more effeicient in taking up glucose in hyper glycemia

G6Pase

oxidizes glucose via glycolusis to cupply muscle with ATP for contraction-->does not release it into the bloodstream

supplies blood with glucose between meals

GLUT4

GLUT2

Enzyme that converts Glucose-6 phosphate (G6P)-->Glucose-1 phosphate (G1P)

condition caused by monosodium urate monohydrate (MSU) crystals in and around the tissues of joints,

elevated serum urate above 6.8 mg/DL

age (serum urate increases with age, gender (women get symptoms after menopause, men 10 yrs after puberty), diet (high in purines)

stage 1; acute gouty arthritis, stage 2: intermittant gout, stage 3: chronic gouty arthritis

identification of MSU crystals in synovial fluid leukocytes

deficiency in HPRT-->leads to increase in PRPP, guanine and adenine-->increase urate levels, only incident of prepubescent gout

treatment for gout that blocks the activity of xanthine oxidase-->stops the conversion of purines to urate

take a sample of tophus fluid

order cell count, gram stain, crystal analysis

occurs in the cytosol,, branches from glycolysis, generates pentose phosphates for synthesis of RNA and DNA, important for RBCs, generates NADPH (anabolic)

generated from pentose phosphate pathway found in liver, adrenal cortex, RBC, involved in the biosynthesis of fatty acid, cholesterol, steroid hormones, bile salts

NADPH/NADP+= 10/1 NADH/NAD+=1/1000

reduction of glutathione (GSH), maintenance of reduced glutathione, fatty acid and steroid synthesis

AN ANTIOXIDANT (made of: SH+ glycine + cysteine + glutamate) maintain membrane integrity in its reduced state

gets energy by converting glucose into two molecules of lactate-->gains 2 ATP

10%

No, they are irreversible

Yes

1. G6P (NADP+-->NADPH + Glucose-6 phosphate dehydrogenase) -->6-phosphogluconolactone, 2. 6-phosphogluconolactone (lactonase) --> 6-phosphoglucanate, 3. 6-phosphoglucanate is oxidatively decarboxylated (6-phosphogluconate dehydrogenase, NADP+-->NADPH)-->ribulose-5-phosphate

6-phophogluconolate (lactonase, NADP+-->NADPH)-->6-phosphoglucanate dehydrogenase, Irreversible and not rate limiting

Causes hemolytic anemia due to inability to detoxify agents (owing to insufficient amt of reduced glutathione)

class 1 (very severe, 2%) --> class IV (none, 60-150%)

To create NADPH: transketolase and transaldolase convert carbon skeletons of 3 molecules of ribulose-5-phosphate -->form 2 molecules of Fru-6-P and one Glyceraldehyde-3-P

To create riboseL nonoxidative reactions can synthesize ribose-5-P from Glyceraldehyde-3-P

Thiamine diphosphate (TPP) is cofactor for transketolase, need thiamine for pentose 5- phosphate production

cofactor for transketolase, pyruvate carboxylase, alpha-ketoglutarate dehydrogenase (TCA cycle), brnached alpha keto acid dehydrogenase

reduce TPP-->reduce the amount of NADPH synthesis via pentose-5 phosphate pathway

cytoplasm of hepatic cells (liver)

HMG CoA reductase

Cleave phospholipids-->make Arachadonic Acid

synthesized in membrane-->made from AA-->signal via G-proteins made via COX 1 and COX 2

made from arachadonic acid via lipoxygenases

made from AA via cytochrome P450--> 20-HETE implicated in hypertension-->inhibited by NO/CO

cyclooxygenase 1, constituitive found in platelets, kidney and stomach

inducible, responsible for imflammatory prostaglandin synthesis

NSAIDS-aspirin, tylenol-->irreversibly inactivates COX 1 and 2 by blocking PGG2-->block production of thromboxane (vasoconstrictor) and clot builder

celecoxib and rofecoxib

Prednisone-->inhibits PLA2 from converting DAG to arachadonic acid

used to convert AA to 5HPETE

used to convert AA to 5HPETE

Activated leukocytes-->send signals for PLA2 to cleave membrane phospholipids-->AA is liberates-->5-LO and FLAP convert AA-->5-HPETE--->LTA4---> converted by LTA4 hydrolase to LTB4

involved in mineral balance, retention of sodium, excretion of potassium, regulating blood pressure

mineralocorticoid, stimulates sodium reabsorption and causes increase in blood pressure

steroid hormones important for anti-inflammatory and stress responses, immunosuppresive

key glucocorticoid, regulates cardiovascular and metabolic function, including stimulation of gluconeogenesis

cAMP-->PKA-->phsophorylates 20-22 desmolase-->forms cortisol

ACTH

Angiotensin II

mixed function oxygenases, converts arachidonic acid-->20 HETE via oxidation

angiotensin II--> DAG + IP3 (IP3 --> Ca2+)-->PKC-->phosphorylates 20-22 Desmolase-->forms aldosterone

20-22 desmolase, cleaves off all but 2 Cs of the side chain on the D ring of cholesterol, regulated by phosphorylation/dephosphorylation via the secondary messenger cAMP-->PKA

21-hydroxylase-->leads tot increased testosterone production--?decreased production of cortisol and aldosterone

cells of adrenal cortex-->produce angionentsin II--> activates the production of aldosterone

pituitary __>releases ACTH-->(regulated by corticaol feeding back and inhibiting productiond of ACTH)

decreased aldosterone production-->NA+ loss-->hyponatremic dehydration

21 hydroxylase deficiency causes lack of cortisol-->no gluconeogenesis-->drop in blood glucose-->hypoglycemia

citrate-->isocitrate-->alpha-ketoglutarate-->Succinyl CoA-->Succinate-->Fumarate-->Malate (shuttle)-->Oxalacetate

NADH and FADH2-->for aerobic production of ATP

generates bulk of ATP for maintaining homeostasis through oxidative phosphorylation

Inner mitochondrial membrane

Complex I-IV on inner mitochodrial membrane + 2 electron shuttles (CoQ and Cyt C) + Complex V generates ATP but has no enzyme activity

NADH Q reductase-->transfer 2 electrons from NADH and proteins to CoQ

succinate DH + Glycerol phosphate DH + Fatty actl CoA DH (+ CoQ electron shuttle)-->2 electronsof FADHs passes on to CoQ along with 2 protons

CoQ is small lipid soluble, diffues and shuttle electrons though membrane to compleX III

cytochrom bc 1 complex-->transfers electons to Cyto C

Water soluble protein-->accepts electons from II and shuttles them to complex IV

cytochrome oxidase-->uses Fe and Cu-->transfers electrons to O2-->1 molecule H2O produced for each molecules of NADH of FADHs oxidized-->4 electrons transferred=4H+-->O2-->2 H2O

NADH

monosodium urate monohydrate (MSU) crystals in and around the tissues of joints

elevated serum urate (hyperuricemia >6.8 mg/dL), recurrent acute arthritic attacks, presence of MSU crystals inside synovial leukocytes, MSU aggregates deposited in and around joint, renal disease

>6.8 mg/dL, anyone with hyperuricemia is arisk for gout

age (older you get the higher they are), gender (women don't get symptoms until after menopause), diet (high in purines like meat, shrimp, animal products)

preceded by asymptomatic hyperuricemia, Stage 1: Acute gouty arthritis, Stage 2: intermittant gout, Stage 3: chronic gouty arthritis

identification of MSU crystals in synovial fluid leukocytes, identification of MSU crystals from tophus

purines made de novo from Ribose 5-P + ATP---(PRPP synthetase)-->PRPP-->IMP--->Inosine-->Hypoxanthine-->Xanthine---(xanthine oxidase)->Urate

Adenine phosphoribosyltransferase (APRT)

Hypoxanthine-Guanine phosphoribosyltransferase (HGPRT)

let you reuptake purines and recycle them

X-linked disorder (pre-pubertal boys) HPRT deficiency--> increase in PRPP, guanine, adenine, urate

treatment for gout, blocks at xanthine oxidase

pKa (level at reactants=products) of uric acid is 6, at night when we are sleeping-->respiratory acidossi-->shifts products to less soluble side

gross appearance, order cell count and differential (look for neutrophils, microbiology culture, gram stain, crystal analysis if gout is suspected-->need resh specimen because solutes can dissolve

polarizing microscope with compensator (MSU found in 90% of acute attacks, lower percent chronically)--can differentiate from pseudogout

normal=clear, slightly viscous, WBCs low, no RBCs, no crystals, negative culture, gout fluid=tubid, opqaue, lots of WBCs, negative gram and culture, MSU cyrstals, negative birefringence

hypertension, obesity, high alcohol intake, high meat intake, hyperinsulinemia, metabolic syndrome

xanthine

xanthine oxidized by xanthine oxidase to form uric acid

provides half the oxidative energy required for liver, kidney, heart and skeletal muscle

Lipid mobilization (TAGs hydrolyzed in adipose tissue to fatty acids plus glycerol)-->transport FAs in blood to the tissues-->activation of fatty acids as CoA ester-->transport to mitochondria via carnitine shuttle-->metabolized to acetyl CoA

TAGs---(via DAG)---> glycerol + FFAs

transport fats

transfer TAGs made in liver

needed for the transportation of long chain fatty (12-20) acidsfrom cytosol into mito matrix

missing the methylmalonyl CoA mutase to convrt odd chain fatty acids to succinyl CoA-->huge build up of methylmalonyl CoA-->metabolic acidosis and developmental retardation

unable to convert B12 to coenzyme form-->flood urine with methylmalonic acid-->huge build up of methylmalonyl CoA-->metabolic acidosis and developmental retardation

propionyl CoA---(biotin as Co2 carrier)-->methylmalonyl CoA---(B12 coenzyme form + methylmalonyl mutase)-->succinyl CoA--->citric acid cycle

Beta-oxidation

alpha-oxidation of phytanic acid (releases CO2)-->now thiokinase can anneal CoA-->proceed to B-oxidation to make acetyl CoA OR propionyl CoA-->succinyl CoA

ackee plant contains hypoglycin-->inhibits medium and short chain dehydrogenases-->inhibits B-oxidations

no carnitine=no carnitine shuttle=you can't do b-oxidation of long chain FAs-->nonketotic hypoglycemia because you can't produces muscle aches and weakness following exercise

absence of peroxisomes in liver and kidneys-->can't degrade very long chain FAs-->accumulation of long chain FAs in the brain

defect in the enzyme phenylalanine hydroxylase which converts phenylalanine--> tyrosine ( unable to break down phenylalanine)-->build up toxic metabolites 2-hydroxyphenylacetic acid, phenylpyruvid acid, pneyllactic acid

some activity, but loss of function

no enzyme

deficient in the enzyme that converts biocytin to biotin-->results in problem in the catabolism of branch chain amino acid

disfunctional protein (hypomorphi or null), deficient cofactor (vitamin), deficient activator protein, deficient transcription factor

deficiency of product-->substrate for th next reaction-->energy (ATP) OR toxic metabolites

serum amino acids, serum ammonia, acylcarnitine (tandem mass spec)

urinary amino acids (UAA metabolites in TCA cycles), urinary organic acids, urinary acylcarnitine (tandem mass spec), GAGs

autosomal recessive inherited, potentially fatal disorders, intolerant of exercise

severe hypoglycemia/poor ketogenesis, sudden infant death, intolerance-muscle disease, heart disease (especiallyin long chain fatty acids), fatty liver

most common (1/60-->1/100 people are carriers), autosomal recessive, point mutation in exon 11, high concentration of Mchain FAs, acyl carnitines, acyl glycines in plasma and urine

2 subunits (alpha and beta)

involved LCHAD

ketoacyl CoA thiolase

toxic baby syndrome can cause the build of of LCHAD in fetal circulation, late in pregnancy mother will develop HELLP syndrome

hemolysis, elevated liver enzymes, low platelets seen in pregnant mothers, caused by an LCHAD deficiency in the fetus

used to detect urinary organic acids in mitochondrial fatty acid oxidation disorders

give MCADs, bypass the block OR give triheptanoin (C7) triglyceride-->KBs can be produced from odd chain FAs