Molecular Nutrition Final Exam

metabolic syndrome

combination of disorders that increase risk for heart disease, diabetes and stroke

3 out of 5 of the following must be present for diagnosis:

high blood glucose, low HDL, high blood triglycerides, large waist circumference, or high blood pressure

obesity

abnormal or excessive fat accumulation impairing health

BMI

body mass index→greater than 25 is overweight and greater than 30 is obese

calculated by taking weight in kilograms divided by height in meters squared

what is the proper nomenclature regarding obesity

NOT obese patients; people living with obesity

what are problems with BMI and better ways to overcome this

BMI does not account for body composition therefore people with a lot of muscle but a low body fat such as athletes may have an overweight BMI without the higher fat percentage normally associated with it

in to overcome is by measuring waist circumference which is associated with visceral fat accumulation or a DEXA scan which measures body composition

how does obesity impact health

immediate effects=excessive extra weight placing more stress on joints, impaired sleep quality, effects on thermogenesis

long term=increased risk for diabetes, heart and liver disease, PCOS

2 types of excessive fat

visceral=surrounding the organs

hepatic=in the liver

Irish obesity rates and policies to overcome this

60% of adults are overweight or obese with the rates doubling in the last 20 years

childhood obesity decreased from 25 to 15 percent

2018 irish sugar sweetened beverage tax may have helped decrease obesity in children

what groups have the highest prevalence of metabolic syndrome in the USA

non-hispanic white men and mexican american women

first law of thermodynamic related to obesity

energy cannot be created or destroyed

its a myth that some people have slow metabolism→when caloric intake doesn’t match expenditure changes in body composition will occur

although food intake is an environmental factor it is genetically encoded->mutations in genes encoding brown adipose tissue metabolism and lipid handling

gene associated with obesity

FTO gene increases risk of obesity due to the impairing ability to control how much food is eaten due it interfering with impulse control

gene associated with poor lipid handling

PCSK9→familial hypercholesterolemia; genetics disorder impacting bodies ability to clear LDL cholesterol from blood so LDL increases

PCSK9 inhibitors versus statins

PCSK9 inhibitors=inject PCSK9 protein which binds to LDL receptors on liver degrading them→LDL remains in blood since liver cannot process it→inhibiton leads to an increase in LDL uptake and synthesis by the liver therefore taking it our of blood; helpful for people with statin intolerance

STATINS: impacts cholesterol production in liver by blocking HMG CoA reductase which is used to create cholesterol

leptin and ghrelin

leptin is produced by the fat cells fullness

ghrelin is produced by gastric emptying hunger

mechanism is leptin and implications in mutation

leptin stimulates the leptin-receptor in the hypothalimus producing POMC which stimulates MC4R on vagus nerve controlling satiety and it also blocks neuropeptide-Y which signals to inhibit hunger

leptin deficiency in children leads to unregaulted appetite→recombinant leptin can be used to restablize weight

GLP-1

glucagon like peptdide-1→triggers satiety=orexigenic; produced by L-cells of intestine and some central nervous system neurones

GLP-1 agonsits

Ozempic and semaglutide; intially prescribed for type 2 diabetes

stimulates glucose clearance so it reduced adiposity and stabilizes weight

how to improve obesity and why is it a problem now

exercise; expending more calories

we are more sedentary and dramatic increase in sugar intake; processing of food leads to pre chewed and lower satiety which stimulates reward center along with novel chemicals impacting celluar functions

diabetes mellitus

condition causing high blood sugar greater than 7 mmol/L

diabetes=pass through(urine) mellitus=maltose sugar

English doctors used to taste the pee for sweetness in order to diagnose while Chinese doctors would put pee on an ant hill to detect sugar

why is fructose more dangerous than glucose

10x more glycation than glucose

markers of diabetes

HBA1C=glycated hemoglobin on RBC; more than 6.5 % means you have diabetes→good indicator because it illustrates last 3 months of blood sugar(red blood cells replaced every three months)

experiments relating to diabetes

1889 Minkowski removed pancreas from dog triggering hyperglycemia

1920 Best injected chilled dog pancreas extract in sick pancreatectomized dog, which led to a decline in blood sugar, illustrating insulin function

Dorothy Hodgkin 1969→ described 3D structure of insulin using x-ray crystallography

islets of the pancreas

composed of beta and alpha cells

alpha=glucagon

beta=insulin

fasted state versus fed state

fasted=glucagon→increased glycogenolysis, gluconeogensis, ketogensis; trying to increase blood sugar to normal level of 5mM/L

fed=insulin→inhbits actions of glucagon and promotes glycogen syntehsis and glucose oxidation to lower blood glucose

what type of transporter allows cell to take up glucose

GLUT transporter→GLUT 2 in the liver and pancrease

GLUT 4=insulin dependent in the skeletal muscle

what organ does not require GLUT transporters

the brain

what does insulin do regarding glycogen synthase

blocks glycogen synthase inhibitor→GSK3 which allows the storage of glucose as glycogen

what happens in the adipose tissue when insulin is high

insulin signaling triggers gene transcription for lipid synthesis

when no insulin is present to get glucose inside the cell

stress hormones increase and the liver triggers other subtrate breakdown to increase glucose levels in the blood which only makes the problem worse; leads to lipid breakdwown and ketosis and the breakdown of the TCA cycle therefore increase in lactic acid production and acidosis

is type 1 or type 2 diabetes an auto immune disease

type 1→T-cells attack the beta cells of the pancreas

Alpha cells survive due to expressing more of the ANTiapoptic gene BCL2L1

what causes insulin resistance

nutrient overload

treatments for diabetes

type 1=insulin

type 2= metformin=acts on liver by activating AMP kinase leading to a starvation type response where gluconeogenesis is inhibited along with promoting catabolic pathways to decrease fat synthesis

excercise→skeletal muscle during excerzie can uptake glucose wtihout the need for insulin

weightloss→less fat means less neeed for insulin

sulfonylureas→when metformin does not work; bumps insulin release in the beta cells when exhausted blood suagr drops however increases fat because insulin increases

how are adipose tissue expansion and insulin resistance linked

through inflammation→immune cells infliltrate adipose tissue leads to accumulation of DAMPS causing systematic ctyokine inflammation

type 2 diabetes

adult onset→insulin signaling loses functions in periphery limiting glucose clearance in the blood due to defective GLUT 4 membrane expression causing insulin resistance

oversimulation of insulin signalling leading to phosphyrlation and degradation of insulin receptor subatres adpaator proteins and inhibiits PI3 kinase activity

• The phosphoinositide 3-kinase (PI3K) signalling cascade, which is activated by insulin, regulates cellular metabolism and cell fate decisions, including cell survival and proliferation.

• High insulin levels can promote and sustain tumour growth.

high GI versus low GI foods

glycemic index in foods how much blood sugar is spiked after eating

PI3 kinase

• The phosphoinositide 3-kinase (PI3K) signalling cascade, which is activated by insulin, regulates cellular metabolism and cell fate decisions, including cell survival and proliferation.

• High insulin levels can promote and sustain tumour growth.

gestational diabetes

placental hormones causing mother to have a degree of insulin desensitization leading to an increase in blood sugar and baby then also being exposed

what causes type 1 diabetes

beta cell destruction→T-cell attacking beta cells of pancreas with 80-90 percent beta cell destruction before symptoms arise

which diabetes is associated with kidney and retina probelms

type 2 because it generally manifests as high blood sugar for long amounts of time causing glycation of proteins

whereas type 1 is diagnosed and controlled in childhood

microvascular function destruction and immunity decrease

what is AGE in diabetes

advanced glycosylated end products leading to micro and macro vascular structure destruction and immunity decrease

describe DKA

diabetic ketoacidosis→lipolysis breaks down fat and the liver forms ketone bodies which causes a drop in pH; more likely in type 1

changes in the anion gap: normally at 12 mEq/L but in acidosis, hydrogen ions are released and bicarbonate binds to them leading to its reduction. Therefore the gap increases to 16 mEq/L

HHS

hyperosmol hyperglycemia syndorme(HHS) type 2 diabetics don’t create ketones rather it is due to the liver over breaking down proteins→no ketones little insulin puts little sugar into the cell→slower onset

why is insulin given in subcutaneous shots and not ingested

it would break down in the digestive system

how do sulfonylureas work

they trigger insulin release in pancreatic beta cells by triggering intracellular flux of Ca2+ promoting insulin release

whos most at risk for lactic acidosis with metformin

kidney failure patients since the kidney plays a role to clears lactic acid

level of blood sugar wanted to be maintained by body

5 mM/L

what happens when blood sugar is low

lipolysis breaks down triglycerides into glycerol and fatty acids

glycerol goes into the Krebs cycle and the fatty acids turn into acetyl CoA, which binds together to form ketones and go to the brain, whereas oxaloacetate is not limited

definition of lipid

macromolecules soluble in nonpolar solvents

are fats or carbs more reduced

fats→9 kcal verus 4 in carbs

nonpolar so fats dont bind to water therefore giving 6x more energy than carbs

describe the process of fat digestion(lipolysis)

1. small amounts of lipid digestion occur in the stomach due to gastric lipase; fats form fat globules

2. majority of digestion occurs in the small intestine since bile is produced in the liver via cholesterol and then is stored in the gall bladder, which gets released into the small intestine

3. this breaks down the large fat globules to allow pancreatic lipase and colipases to break down triglycerides into monoglycerides→micelles=broken down parts of fat surrounded by bile salts

4. microvilli allow the micelles to diffuse into mucosal cells while the bile salts get left behind, where they reassemble into triglycerides and cholesterol and become chylomicrons with the addition of the ApoB48

5. through exocytosis chylomicron goes into the lymph because its too big to go into the blood stream which allows it to go to the organs of the body

what are all of the lipids we consume

fat-soluble vitamins ADEK

cholesterol

triglycerides

small amounts of phospholipids

describe micelles

lipase and colipases breaking down fat globules with the help of bile salts which surround the broken-down triglycerides and cholesterol facilitating the movement into mucosal cells where the bile salts get left behind

what is cholesterol used for

creating cell membranes, sterol hormones, and bile salts

purpose of insulin beta cell in adipocytes

drives fatty acid and glucose uptake while driving triglyceride synthesis and inhibiting hormone-sensitive lipase which detects glucagon and breaks down fat

what food is high in cholesterol

eggs→70% RDA with 211 mg

structure of cholesterol and formula

4 linked hydrocarbon rings; biological steroid; polar end has hydroxyl group that is oriented in membranes with hydroxyl group interacting with phospholipid polar head

C27H46O

is cholesterol required in diet

no in a fasted state, humans will synthesize cholesterol from polymerized isoprene units at about 800 mg per day

what levels of cholesterol and triglycerides are ideal in the blood

describe the steps in cholesterol synthesis

step 1: occurs in the cytosol; acetyl CoA to HMG-CoA via HMG CoA synthase and is regulated by feedback inhibition by cholesterol and its derivates

step 2: occurs in the ER; HMG CoA to mevalonate via HMG CoA reductase RATE LIMITING STEP

step 3: mevalonate to isoprene units

step 4: isoprene units to squalene; condensing 6 isoprene units to form 30-carbon sequence squalene

step 5: squalene to cholesterol; first it cyclized to lanosterol then rearranged into cholesterol

AH HM MI IS SC

A Happy Ham Misses My Ingredients So She Laugh Cries

what’s a focus for statins

HMG CoA reductase→they competitively inhibit

effect of cholesterol on membrane fluidity

sterol hormones built by cholesterol

progesterone-=prepares the uterine lining for pregnancy and maintains pregnancy

androgens including testosterone which is responsible for male secondary characteristics such as deeper voice and body hair and estrogen which is the ovarian cycle

cortisol=promotes gluconeogenesis and is a stress response released by the adrenals

how does cholesterol build vitamin D

1. takes 7-dehydrocholesterol in the epidermis and combines with UVB light to create pre vitamin D3

2. heat is required to convert pre-vitamin D3 to cholecalciferol which gets activated by the liver to vitamin D

   BOTH DONT REQUIRE ENZYMES

discuss bile

made by liver held in the gallbladder→primary bile acids are cholic and chenodeoxycholic, which become secondary bile salts by losing OH at C7 and becoming deoxycholic and lithocholic

bile salts coming from cholesterol or glycocholate and taurocholate which are highly polar and are effective detergents due to having both polar and non polar elements

name the lipoproteins and their functions

chylomicrons: intestinal transport dietary TAGS and cholesterol APOproteinB48

very low density lipoproteins(VLDL): liver transport endogenous synthesized TAGS

Low density lipoproteins(LDLS): deliver cholesterol to peripheral tissues(arteries): B100 proteins

High Density Lipoprotein(HDL): liver;; removes used cholesterol from tissues to liver

purpose of LPL

lipoprotein lipase removes fatty acids of chylomicrons

ATP binding cassette transporters

ABCA1 and ABCG1: in cell plasma membrane and regulate the removal of cholesterol from cells to HDLs

how does LDL get into cells to deposit cholesterol

through receptor-mediated endocytosis with its APO B-100 protein

process of HDL lowering cholesterol

the free cholesterol is converted by LCAT to cholesterol esters and placed inside HDL along with TAGS and then CEPT facilitates

the transfer of CE to VLDL and the VLDLs TAGS to HDL where the VLDL then brings the cholesterol to the liver to create bile

why do people with anorexia have high cholesterol

they have lower T3 levels due to downregulation of the thyroid and T3 is a regulator of CETP so it becomes dysregulated and thus an increase in cholesterol is seen

alchhol formula

CH3CH2OH

elimination rate of alchol

about 150 mg per hour with the liver doing about 9” percent of this while the remained gets excreted in urine, breath, sweat and tear

what amount of alchohol is metabolically produced

.39mg/liter

alchohol content of beer

.5L of beer with 4 % alc content contains 16g of ethanol

digestion of alchohol not inculuding enzymes

rapidly uptaken from digestive system through diffusion and the max blood alchol level reached at about one hour after consumption and it gets rapidly distributed throughout all tissues with most uptaken by muscle and the brain

what is the lethal amount

.3-.4 percent alchol in the blood

how is alchohol metabolized in the liver

1. alcohol dehydrogenase oxidizes ethanol into acetaldehyde

2. aldehyde dehydrogenase oxidizes to acetate

3. acetate gets converted to acetyl CoA by acetate CoA ligase in ATP dependent reaction

   another ADH substrate is methanol which a lot of people have recently died from in Asia due to drinks being homemade or having methanol added because it is cheaper and this breaks down to deadly formaldehyde

Asian flush

50% of asian have inactive ALDH which causes flushing elevated heart rate and nausea and vomiting→disulfram inhibits ALDH so it is used to help alcholhic

describe the mortality of alchohol in a graph

its a U shaped curve with 1-2 drinks per day decreasing risk of death and and more than that increasing

how does moderate alchol consumption influence HDL and what a compound in red wine that is healthy

increases by about 12 percent and resveratrol prevents platelet stickiness

why does alchohol cause liver damage

increases NADH and acetyl CoA which inhibits krebs cycle activity and encourages synthesis of fats and cholesterol therefore increasing fatty acid storage in liver

cirrhosis=chronic alchohoism and it kills liver cells and some liver functino tests are albumin and bilirubin

why is alchol bad for the brain

free radical build up alters cerebellum which leads to impaired thinking and slowed speech

what causes nausea with alchohol in the brain

5-HT3

alchhol effects on the brain and dependece

GABA=increased=inhibitory neutrotransmitter stops neurons from firiing

glutamate=excitaitry neurotransmitter

alchohol is a depressant because it increases GABA and inhibits glutamte

for a neuron to fire Ca2+ needs to jump into the neuron and this flow is decreased with alchohol

in response the brain decreased GABA receptors and increases GLUTamate recpetors thus causing anxiety and seizures in withdrawl due to overacitivity and increased Ca2+ flow

patients are given benzos which enhance GABA at the recpetor to increase relaxation

2 types of alcohol subtypes

type 1=mileiu limited→late onset high reward and harm avoidant

treatment=interaction skills

type 2=male limited→early onset, genentic, novelty seeking

treatment=coping skills

whats used to diagnose alchoholism

AUDIT→alchohol use disorder identificiation test

blood alchohl levels to drive and die

driving is .08 and death is .3

describe the reward pathway

VTA releases dopamine and the nuclease accumbens is sensitive to dopamine and the prefrontal cortex processes what is making the organism feel rewarded

example of experiment with the reward pathway

animals will bar press repeatedly for intracranial injections of alchohol into the VTA