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

cytoplasm of liver parenchymal cells

emulsify fats (soap molecules, hydrophobic on one side hydrophilic on the other)

mainly ionized

7-alpha-hydroxylase enzyme (CYP7A1)

rate limiting enzyme in bile acid production, installs the OH group at position 7

by bacterial enzyme cleave og primary bile salts in intestines

hormones

portal vein

30g

2%

HMG CoA reductase

bile supersaturated with cholesterol

made from cholesterol

C21 steroid hormones (Ex.progesterone) made in the adrenal cortex

C19 steroid hormones (Ex.androgens) made in the testis

C18 steroid hormones (Ex.estrogen) made in the ovary

preprocessed to be more water soluble then excreted via the kidney --> in urine

act via nuclear action

act via cytoplasmic receptors to form steroid-receptor complex--->receptor dimerizes-->nuclear localization signal exposed-->complex enter nucleus and binds to SRE (specific response element)-->functions as transcription factor-->enhance/repress gene expression

Zinc Finger on the receptor feels the DNA to find the palandromic

it has four cysteine instead od 2 cysteines and 2 histidines

synthesized in pancreatic beta cells, anabolic hormone-->acts to decrease glucose in the blood

synthesized in pancreatic alpha cells, catabolic hormone-->action to increase blood glucose

preproinsulin-->signal peptide cleaved=proinsulin---->C-peptide cleaved= insulin

phase 1, five steps (glucose comes into B-cells-->glucose is phosphorylated-->glycolysis-->increase in ATP-->close ATP gated K channel-->depolarization-->open voltage gated Ca channels-->trigger insulin release

because GI hormones help to increase insulin secretion

dimerizes tyr-kinase receptor-->autophosphorylates-->phosohporylates IRS1-->activated a lot of pathways-->recruits GLUT4 to membrane

Glucose-6-phosphatase-->can't release glucose in the bloodstream

independent, it is always one regardless of insulin level

dependent, glucose transport in muscle and adipose tissue depends on insulin levels

carbohydrate, lipid, protein, ALSO PROMOTES POTASSIUM UPTAKE

intracellularly, 90% is inisde the cell waiting to be mobilized to plasma membrane

insulin doubles recruitment of GLUT-4 receptors to plasma membrane

Defective insulin signaling (also, decreased # and affinity of receptors)

impaired glucose tolerance

post-receptor signal transduction defects (defective tyr-kin, mutations in genes coding for IRS1, defective translocation of GLUT2 to cell membrane)

mobilizes glucsoe from every available fuel source, increases lipolysis and ketogenesis from acetyl CoA

binds to its own receptor via G-protein couple proteins-->activates Adenyl Cyclase-->activates cAMP cascade--> activates PKA-->phophorylates PFK2-F2,6BPase-->activates F2,6BPase-->stimulate gluconeogenesis

No

Epinephrine stimulates glycogenolysis and gluconeogenesis (and inhibits glycolysis and lipogenesis)

alpha and beta adrenergic

epinephrine

fork-head winged-helices, transcription factors that promote gluconeogenesis, synthesis is regulaated by insulin

promotes gluconeogensis in the liver in the fasting states by inducing the PEPCK and G-6-Pase enzymes (insulin phosphorylates foxo1 to blocks gluconeogenesis)

regulates fatty acid oxidation in fasted state by induing genes encoding for enzymes of glycolysis, FA oxidation and ketogenesis (insulin phosphorylates foxa2 to inhibits FA oxidation)

>126 mg/dL fasting glucose or >200mg/dL after glucose tolerance test

<110 mg/dL

110

allows recycling of lactate (from muscle anaerobic glycolysis) back to glucose (in liver) via gluconeogenesis

allows recycling of alanine (from muscle proteolysis) back to glucose (in liver) via gluconeogenesis

hypermetabolic state

epinephrine, glucagon, cortisol-->stimulates catabolism (glycogenolysis, lipolysis, proteolysis)

yes-->glucocorticoid hormone (GLUCAGON) stimulate gluconeogenesis by encoding genes for G6Pase and PEPCK

hyperglycemia and vascular complications

oxidative damage of the small (microangiopathy) and large (macroangiopathy) arteries via ROS and AGE products

kidney (diabetic nephropathy) and retina (diabetic retinopathy)

caused by glycated proteins through sorbitol oxidation

insulin independent, insulin resistant caused by B-cell failure

caused by autoimmune attack of pancreatic B-cells (insulin-dependent)--> leads to fasting hyperglycemia

polyuria, polydypsia, ketonemia (increased blood ketone bodies), ketonuria, overproduction of acetoacetic acids, metabolic acidosis

HLA genes on chromosome 6, siblings have 10% increased risk of Type I diabetes if their siblings are affected

macrovascular components-->leads to coronary artery disease

glycated hemoglobin, most highly studied (AGE) glycated proteins

Advanced glycated endproducts-->bind to membrane receptor-->make ROS-->recruit inflammatory proteins and cytokines

glucose-->sorbitol

caused by sorbitol build up in the brain/nerve tissue

insulin increases cellular uptake

lack of insulin= K efflux from cells-->osmotic diuresis-->

A,D,E,K-->stored in tissues (not as readily extracted from diet as watr soluble vitamins)

stored in liver, 3 compounds: retinol, retinoic acid, retinal-->retinoic acid most active, visual pigment rhodopsin found in the rod cells of the retina

Beta carotene

common most cause of blindness in the world (defective night vision-->prgressive keratinization and blindness)

leads to bone loss, hair loss, hepatosplenomegaly. nausea, vomiting

is really a hormone, usually only vitamin required in diet, produced by the action of UV light on provitamins (7 dehyydroxycholesterol)

insufficient sunlight, increased vitamin D metabolism due to low calcium intake

Vitmain D deficieny Rickets as a result of deficiency of calcium mineral (low circulating calcium concentrations

causes enhanced calcium absorption and bone reabsorption-->leads to hypercalcemia and calcium deposition-->develop kidney stones

mixture of several compounds alled tocopherol and present in 90% of human tissue, richest sources are vegetable oils and nuts

Vitamin E, prevents free radical damage by donating hydrogen to free radical

neurological symptoms, hemolytic anemia, thrombocytosis

necessary for blood coagulation, absorption of vitamin K depends on appropriate fat absorption ( like vitamin E), dietary sources green leafy vegetavle, dairy, veg oils

by intestinal microflora-->ensure dietary deficiency does not occur

can occur rarely in newborns with bleeding disorders (given a shot of Vitamin K at birth because the gut of a newborn is sterile)

antithrombin drugs

with the exception of vitamin B12, the body has no storage capacity for water soluble vitamins, No toxicity associated with excess, any excess is excreted in urin

Act as coenzyme, Not toxicity associated with excess

essential for carboxylation reaction and carbohydrate metabolism, deficiency associated with alcoholism and Beri-Beri disease

alcoholism and Beri Beri disease, early sign are loss of appetite, constipation and nausea

thiamine deficiency resulting in ataxia, neuropathy, loss of eye coordination

associated iwth oxidoreductase, attached to sugar alcohol ribitol, found in oxidoreductases as FMN and FAD, required for energy metabolism

causes inflammation of the mouth and tongue, scaly dermatitis-->Pellagra

erythtrocyte glutathione reductase activity

required for NAD+ and NADP+ synthesis-->oxidoreductase reactions, synthesized from tryptophan in liver

important in amino acid metabolism and participates as cofactor for amino acid metabolism especially transamination and decarboxylase

causes irritability, nervousness, depression-->leads to neuropathy, convulsions and coma

Important in carboxylation reaction, lipogenesis, gluconeogenesis, catabolism of branched chain AAs, normally synthesized by intestinal flora

consumption of raw eggs can cause biotin deficiency because egg white protein, avidin, combine with biotin preventing its absorption

part of CoA

important in single carbon transfer reactions such as methylation reactions in metabolism and gene expression

leads to hyperhomocysteinemia-->increased risk of cardiovascular disease

folic acid

folic acid-->enlarged blast cells in bone marrow

pregnancy--due to increased demand

Similar structure to heme, excpet Iron replaced by cobalt, participates in recycling of folates, found only in food of animal origin

megaloblastic anemia characteristic of B12 deficiency-->due to reduced folate and accumulation of methyl THF

vitamin B12

active form is ascorbic acid-->oxidised to generate vitamin E-->essential nutrient in humans-->fragile and easily destroyed, found in citrus fruits

Vitamin C

causes scruvy-->hemorrhages, muscle weakness, soft/swollen/bleeding gums, poor wound healing

Vitamin C

by lowering homocystein concentration

metal ions required as active components in proteins

affects growth, skin integrity, wound healing

causes skin lesions, sexual impairment, loss of hair (in patients with burns, and renall damage)

copper scavenges oxidase and other ROS, associated with cytochrome oxidase and superoxidedismutase, also important in crosslinking collagen

through bile--chronic excessive copper intake results in liver cirrhosis

Copper

forms part of antioxidant enzyme glutathione reductase peroxidase

found in mushroom-->leads to hemolytic anemia

bound to albumin, small Vd (mostly in plasma), often hydrophilic, often renally excreted, less extensively metabolized

Bound to alpha1-acid glycoprotein, often lipophilic (distrubted more in tissue), usually metabolized (first pass)

LPL gene defect, Autosomal recessive, increase in chylomicrons, find erruptive xanthoma, hepatoslpenomegaly, pancreatitis

apoE gene defect, Autosomal dominant or recessive, increase in chylomicrons and VLDL remnants, symptoms: xanthomas, CHD, PVD

defect in LDL receptor, autosomal dominant, increased LDL, symptoms include tendon xanthomas and CHD

defect in apoB-100, autosomal dominant, increased LDL, symptoms include tendon xanthomas and CHD

Rare

low

ABCA1 deficiency-->results in low levels of HDL

increase

alcohol,exercise, estrogen

obesity, smoking, type II diabetes, malnutrition, anabolic steroid, beta blockers

autoimmune disease, type II diabetes

renal insufficiency, hypothyroidism, menopause, nephrosis

statin, decrease LDL levels, increased HDL, decreases triglycerides

Fibrate, for hypertriglyceridemia, functions as PPAR-alpha agonist, stimulate beta oxidation of FAs, stimulate lipoprotein lipase activity

inhibits lipolysis by blocking hormonsensitive lipase, stops FFAs from being mobilized from adipocytes, inhibits triglyceride synthesis-->decrease synthesis of LDLs, INCREASE HDL, decrease Lp(a)

both treat hypertriglycerimedia, use Niacin is patient is on Warfarin

undergoes first pass metabolism, converted to NAD and other metabolites because excreted in urine

cutaneous flushing due to prostaglandin release-->corrected with administration of aspirin

increase beta-oxidation , increase lipoproteinlipase activity, adjunct therapy in combo with other drugs

Bile acid binding resin, anion exchange resins that bind up bile acids and bile salts in small intestine

decrease LDL, can combine with statin, prevent reabsorption and enterohepatic recirculation of bile,indirect way of depleting the body of cholesterol

interfere with the absorption of anionic drugs, and fat soluble vitamins (ADEK)

inhibits the absorption of cholesterol at the brush border of the small intestine (adjunct) only effects exogenous cholesterol taken in by food (30-40%)

oral, very water soluble, intestinal glucuronidation facilitates absorption (usually glucuronidation decreases absorption)

grapefruit juice (DHB) and nifedipine

CYP 3A4

ketone bodies

HMG CoA lyase

Transmethylglutaconate shunt (escape hatch)

36

18

16

Pentose phosphate pathway

ACAT

inhibiton of cholesterol biosynthesis and inhibition of LDL receptor

inhibited, downregulated, activated

brings SREBP to the protease-->activates SREBP--->activates transcription of LDL receptor and HMG CoA reductase

25-hydroxycholesterol

oxysterols

apoA

moves cholesterol from the peripheral tissue-->HDL

Steroid hormones can directly effect gene transcription, whereas polypep can only indirectly affect gene transcription

Cannot cross membrane, must bind to cell surface receptors and initiate effects via second messengers (cAMP, Ca2+, etc)

Nitric oxide

give angina patients glycerol trinitrate-->convert to NO-->NO stimulates guanylate cyclase-->changes intracellular Ca2+-->dilation of blood vessel

C20 unsaturated fatty acid, lipid 2nd messenger or inflammatory messenger

second messengers synthesized in membrane from AA, signal via G-coupled proteins, made via COX-1 and COX-2 enzymes (prostaglandins, prostacylins, thromboxanes, leukotrienes)

Made from AA via lipoxygenases

a fatty acid

leukotriene and prostaglandins

eicosanoid, fever inducers

eicosanoid, vascoconstrictors

eicosanoid, vasodilator

COX-1 and COX-2

peroxidase

lipoxygenases

cytochrome P450

CO/NO

Regulate inflammation, regulate blood flow to organs, control ion transport, induce sleep, vasoconstriction, platelet aggregation

from AA in membranes

Prednisone, enzyme: PLA2

aspirin, ibuprofen, acetominophen (inhibit COX-1 constituitive, COX-2 constituitive)-->affects large organ system (renal GI)

celecoxib and rofecoxib, inhibit the inducible COX-2, specifically ontrol pain, fever, inflammation

irreversibly blocks COX1 and COX2 by acetylation, preventing the production of PGG2

cyclooxygenase 1, constiutive, found in platelets, kidneys and stomach

inflammatory and vasoactive mediators, formed from cleaving arachidonic acid by lipoxygenases

converts AA-->5-HPETE this makes-->leukotriene A4

regulator of lipoxygenase enzymes, could be a drug targets

40% of myeloproliferative disorders (leukemias)

asthmatic and allergic reactions

neutrophils (chemoattractant)

neutrophils and monocytes

macrophages

omega-3 has a double bond at the 3 position, omega-6 has no double bond at the 3 position

omega-6

anit-inflammatory

prostaglandins and leukotrienes (less inflammatory for omega-3, more inflammatory for omega-6)

yes

flax seeds, salmon, walnuts, alpha-linolenic acid (ALA)

10:1

reduce inflammation by upregulating anti-inflammatory proteins, 2 classes (immunologic and metabolic), metabolic increase gluconeogenesis (Ie, cortisol)-->stimulate fat breakdown in adipose tissue to generate FFA

regulate water and salt balance (Na+ retention), aldosterone acts on the kidneys to activate reabsorption of sodium and passive reabsorption of water, active secretion of K, major function in blood pressure and blood volume

mineralocorticoid hormone, aldosterone produced in the adrenal gland and secretion mediated by angiotensin II (also by ACTH) and local potassium levels, that is activated by PKC

conversion of cholesterol to pregenenolone via 20,22 desmolase-->this is limited by the supply of cholesterol in the inner membrane

cortisol

aldosterone

via phosphorylation (cAMP-->PKA-->phosphorylates 20,22-desmolase)

ACHT->cAMP-->PKA-->phosphorylates 20,22-desmolase

angiotensin II-->increase IP3 and DAG-->cAMP-->PKC-->phosphorylates 20,22-desmolase

in combination with NADPH, FAD, Fe3+, O2 to form hydroxylated product

21-hydroxylase

The underactivation of renin (converts angiotensinogen-->angiotensin) because of a lack of aldosterone-->results in decreased sodium and water reabsorption by the kidneys

Niacin

increases

riboflavin

pyruvate is getting reduced (NADH gets oxidized-->NAD+)

electron transport chain

glycolysis and succinyl CoA-->succinate (releases GTP)

oxidative, exergonic

reductive endergonic

in extreme exercise conditions

80-100g

some energy generated from anaerobic splitting of a phosphate off of phosphocreatine-->maximum energy tield in about 10 seconds

takes ATP-->ADP (releases energy)

regenerates ATP by: PCr + ADP--> Cr + ATP

relies mostly on carbs

relies more on fat

mostly fats-->you have to slow down

carbs (anaerobic)

1,3 BPG, PEP, A third is creatine phosphate that has enough energy to synthesize ATP

H2O and CO2

allosteric

PFK-1

AMP (activates), ATP and citrate (inhibits)

F-2,6-BP

G6P

covalent: phosphorylation by PKA, allosteric: ATP and alanine

allosterically activated by AMP-->know ATP is low-->activates pathways that generate ATP (B-oxidation of fatty acids, glucose transport)-->inhibits those that require ATP (fat synthesis, PCr, Cholesterol synthesis)

Glyceraldehyde-3-P and DHAP

Fructose-->Fructose-1-P--(F1P aldolase)--> DHAP

F1P aldolase deficiency-->build up in F1P-->decrease in available phosphate-->looks like G1P so acts as competitive inhibitor for glycogenolysis-->HYPOGLYCEMIA

accumulate gal-1-P and galactose-->enlarge liver, jaundice, cataract formation, cataracts (build up of galactitol-->product of galactose in the lens)

cannot convert FAT to CARBOHYDRATE

TPP (B1), FAD (B2, riboflavin), NAD (B3, niacin), CoA (B5, panthothenate), lipoic acid

NADH and CO2

PDH kinase and PDH phosphatase

blowing off CO2

it is needed in the malatae shuttle to convert malate back to oxaloacetate in the cytosol

fasting hypoglycemia, neonatal hypoglycemia, alcoholic hypoglycemia

catalyzes first step in gluconeogenesis, converts pyruvate to oxaloacetate, happens in mitochondrial matrix

Biotin, B5, Acetyl CoA, ATP

converts oxaloacetate to PEP, happens in cytosol, regulation is mostly transcriptional response to glucagon-->CREB-->cAMP, allosteric inhibition by ADP

converts G-6-P to glucose (only in liver, NOT IN MUSCLE), happens in the smooth ER and regulated by transcriptiona (glucagon-->CREB-->cAMP)

deficiency in muscle glycogen phosphorylase-->abnormally high muscle glycogen because you are not breaking it down-->causes weakness, cramping, decreased serum lactate

Deficiency in Glucose-6-phosphatase (G6Pase)-->glycogen accumulation in liver and kidney-->hypoglycemia, ketosis

Lysosomal alpha-1,4 glucosidase-->glycogen accumulation in lysosomes, early death, normal blood glucose, normal glycogen structure, heart

deficiency in debranching enzyme-->abnormal glycogen with short outer chains, hypoglycemia

deficiency in Branching enzyme-->abnormal glycogen, having long unbranched chains, early death due to cardiac and liver failure

Deficiency in liver glycogen phosphorylase-->abormally high content in liver glycogen, mild hypoglycemia and ketosis

Dietary restrictions (high protein, low carb)

opsonization, phagoctosis, recruitment of other inflammatory cells, MAC complex

involved in all 3 complement pathway

Kinin, clotting, fibrinolytc, and complement

Intrinsic and extrinsic involvve Factor X-->produces soluble fibrin

To break down fibrin you use fibrinolytic pathway

Intrinsic and extrinsic involvve Factor X-->produces soluble fibrin

Plasmin iniaties degradation

Kinin, clotting, fibrinolytc, and complements

is synthesized in the liver: Hageman factor, Involves the cleavage of a few peptide bond to activate the clotting cascade and the kinin cascade

minutes to day, rapid onset, neutrophils (last 2-3 days in tissue), restoration

weeks to years, prolonged duration, macrophages and lymphocytes (B and T cells), angiogenesis

cardiovascular disease, obesity, type II diabetes, chrons disease

always present, always present, neutrophils and macrophages, natural killer cells

Normally silent, componets are lymphocytes (B and T), B lymphocytes generate antibodies and T lymphocytes, cytokines

involves innate and adaptive immune system

epithelial and mesenchyma; ce;;s

TNF, IL-1 IFN-gamma

macrophages have a huge amount receptors for oxidized and glycated LDL

T helper cells release IFN-gamma and signals MF to send signals to pro-inflammatory cytokines

lower LDL, do not lower HDL (olive oil, walnut oil, avocado)

lower LDL but also lower HDL (fish oil)

type of polyunsaturated fat, helps reduce the triglycerise

BAD! Increase LDL cholesterol

Leads 23% decreased of death risk, high fruit, potato, beans, nuts, seeds, whole grain bread, olive oil, wine, little dairy

the less inflammatory prostalgin

fever inducing prostaglandin

enzyme that participates in the cleavage reaction for glucogen phosphorylase

genetic defect, lacking TPP then you can't convert Pyruvate-->acetyl CoA, causes lactic acidosis

alcoholics and anorexia

All amine groups ge converted to Glutamine or urea

starvation, uncontrolled diabetes, infection, trauma

pregnancy, lactation, growth

deficiency in proten and calories (chronic)

deficiency in protein (onset precipitated by increased demand) not necessarily lacking in diet could be inability in protein synthesis

Marasmus has muscle wasting, albumin is moderately diminished and no body fat, Kwashiorkor has Edema and Hepatomegaly in still has some body fat, severely diminished serum albumin, normal insulin and cortisol levels

alpha-ketoglutarate

autosomal recessive, Deficiency in BCKA DH, so you can't degrade BCAAs, you get elevation in BCAAs, keto-acids and alpha-hydroxyacids in urine, vomiting lethargy, severe brain damage

anti-apoptotic protein, homologue of ced9, BCL2 is associated with mito and somehow associated with blocking the release of cytoC, overexpression in B Cell lymphoma

there are two types of proteinsin the BCL family, BH3 only and BH3+other, can be pro or anti apoptotic

proteases responsible for apoptosis, analogue in C. elegans is ced-3 (but in humans there are 14 different caspases), they are cystein dependent aspartate directed proteases AspHole, exist as zymogen activated by cleavage

Apaf-1 (ced-4 homologue), ATP, cytochrome C (comprise the apoptosome)-->this starts the activation of the initiator caspase 9

pro-apoptotic, in the BCL family-->cause the release of cytoC

put the helical tail in the active site, sterically occluding their own active site (like CDKs), and inactivating them

have an open, hydrophobic BH3 pocket, and are active

Hydrophobic pocket is occupied by the BH3 domain of a pro-apoptotic, frees up the pocket of pro-apoptotic protein-->get apoptosis

caused by a dietary deficiency of folate or B12

Cyp 2C9

2 pyruvate, 2NADH, 2ATP

2 lactate and 2 ATP

Glyceraldehyde-3-P

used NADH to convert pyruvate to lactate-->generates NAD+

decrease (50% by 14 days)

increase in synthesis, increase degradation, overall net decrease in protein

negative

negative

catabolic

increase, hyperglycemia

hypermetabolic

converts (valine, leucine, isoleucine) BCAA-->BCKA

converts BCKA to BCKA analogues (propionyl CoA, acetyl CoA, acetoacetyl CoA)

essential amino acids

G6P DH, Heinz bodies

most common human enzymes deficiency

PPP, converts G6P-->phosphogluconolactone, IRREVERSIBLE

converts 6-phosphogluconolactone-->6-phosphogluconate, IRREVERSIBLE

converts 6-phosphogluconate--> ribulose 5-P

HYPOGLYCEMIA IS A COMMON SYMTPOM

transcription factos for fatty acid oxidation, targeted by Fibrates--fibrates are a PPAR agonist

VLCAD, LCAD, MCAD, SCAD

MCAD, on exon 11

HADHA alpha subunit, HADHB beta subunit, LCHAD on HADHA

involved in HELLP syndrome, on the HADHA alpha subunit

hemolysis, elevated liver enzymes, low platelets, LCHAD deficiency in the toxic baby

mostly nutritional, goal to stabilize day to day, avoid catabolic events

Try to supplment diet with medium-chain triglycerides

can't stay warm because these control the white/brown fats

anabolic process, replenishing the pool with odd chain FAs

7-alpha hydroxylase (CYP7A1)

peptidases

cholecystokinin

after pre-processing in the liver--> excreted via the kidney in the urine

zinc finger (2 zinc fingers because recptors dimerize

steroid hormones bind to receptor which binds specific response elements (transcription factors)

have 3 cysteine residues instead of 2 cysteine 2 histidine

True

Pancreatic beta cells-->formed as pre-proinsulin-->signal peptide cleaved-->proinsulin-->C-protein cleaved-->insulin

RER of pancreatic Beta cells

C-peptide

Glucose comes in through GLUT2-->phosphorylated by Glucokinase-->increase in ATP--> close ATP-gated K channel-->depolarizes cell--> Opens Ca2+ channels-->triggers release of insulin

leucine, arginine, lysine

GIP, cholecystokinin (also signals release of bile), GLP-1, and VIP

Because IV would bypass the GI hormones that potentiate insulin secretion

glucose binds insulin receptor--->tyr-kin-->IRS-->GLUT 4 brough to membrane

increases K uptake in cells

post-receptor signaling transduction defects, defective insulin signaling

selenium

Potassium

Vitamin C

Tryptophan

Vitamin K

Vitamin A

Acetyl CoA

FAD

Biotin

Thiamin/TPP

Folic acid- B12 (homocysteine+methylTHF-->mehtionine +THC)

Vitamin E

Vitamin D

Vitamin K

Carnitine

Niacin

B12

B12

B12

B12

Hyponatremia- people drink lots of water, but not sodium, also gives credit for electrolytes

Chromium

Calcium

Water soluble/B vitamins are susceptible to damage by high heat while cooking

antioxidant

riboflavin

Pyridoxine B6

glycogen synthase and transaminase

Phosphorous

Vitamin D

Thiamin

Because of its role as an antioxidant

Anemia

deficiency in B12-->prevents production of folate

Copper