Week 4 Flashcards

Question

Vitamin B7 - what does it do? - co-factor for what enzymes? - deficiency - what can it help with anatomically?

Answer 1

- promotes carboxylation reactions at cellular levels - Pyruvate carboxylase (Carboxylates pyruvate, reduces oxaloacetate from TCA-- Conversion of pyruvate to oxaloacetate is the first step of gluconeogenesis) and Acetyl CoA carboxylase (Carboxylates Acetyl CoA to produce Malonyl CoA which goes into fatty acid synthesis - yes, raw egg whites has anti microbial agent called Avidin which binds to Biotin and prevents its absorption. If 2 or more raw eggs a day eaten, overtime they become Biotin deficient. However, We don't normally get biotin deficient bc intestinal bacteria make it - adequate level helps with skin, nails, hair, etc.

Answer 2

- catalyzes reaction of methyl group from MTHF to homocysteine which converts it to methionine; if not enough then MTHF builds up and THF cant be recylced - macrocytic anemia with hypersegmentation of neutrophils - B12 and folate are needed for DNA synthesis. - Demyelination from B12 deficiency

Answer 3

- Loss of memory, Disorientation, Mild chest pain. Macrocytic anemia, Folate levels low - there will be autoimmune attack against parietal cells within stomach; - parietal cells make intrinsic factor and acid production - GI disturbances (difficulty digesting bc not enough acid in stomach) - Antibody against intrinsic factor and Anti parietal cell antibodies (more specific to autoimmune gastritis) - B12 (cobalamin) and folic acid supplementation give a dose of 1000 micrograms of B12 IM once a week for about a month, then recheck levels, If levels come up then do maintenance dose of once a month injections

Answer 4

pan gastritis

Answer 5

- use cyanocobalamin (synthetic form) because it is easiest and cheapest to produce; however, Vast majority of people can probably convert cyanocobalamin into Vitamin B12, but there may be some people with single nucleotide polymorphisms that can't make the conversion quite as well - Methylcobalamin and Adenosyl cobalamin are the bioactive forms within the body, so for some people that may be more helpful for them

Answer 6

- comes into body as dihydrofolate, which is then reduced to tetrahydrofolate by DHFR because THF is the biologically active form of folic acid - THF, in folate cycle, picks up methylene group and become methylene tetrahydrofolate (MTHF)which will then donate methyl group to dUMP (deoxyuridine) converting it into dTMP making thiamine and Formyl Tetrahydrofolate (FTHF). FTHF then donates single carbon groups to help in synthesis of purines. - folate deficiency, you have enlarged erythroblasts without well developed nucleus. Large in size bc cytoplasmic activities happening ok in blast cells but bc the low levels DNA and RNA, division not happening well. Cell uses all energy to grow big and they appear as megaloblasts in the peripheral blood smear.

Answer 7

- Increase in homocysteine and affects rest of cycle as well. - super common, heterozygous mutations in this gene occur in up to 2/3 of population. - Important to have good sources of folate in diet. For homozygous mutations, may want to go straight to bioactive form of 5 MTHFR supplement.

Answer 8

give more folic acid to patient, everything gets stuck as MTHR and at one point there's no THF recycling

Answer 9

B12 helps add methyl group to homocysteine making methionine which then picks up adenine group from ATP to form SAM (S Adenosyl Methionine) which will donate its methyl group for different Methylation reactions - With B12 deficiency, once SAM gives off methyl group, recycles back to homocysteine and build up of homocysteine results in neuro toxicity - In order to prevent Homocysteine build up, supplement with B6 bc it helps converts excess homocysteine to cysteine

Answer 10

- Retinol: transport form; has OH group - Retinal: important for visual cycle; used by rods and cones - Retinoid acid: modifies gene expression so important for cellular growth; in skin creams; has COOH - Retinaldehyde: storage form in liver of animals; has aldehyde - Beta carotene: precursor of vitamin A, will make 2 molecules of retinol, broken down by Beta carotene dioxygenase

Answer 11

- get retinal ester (storage form) vs getting beta carotene - absorbed and converted to retinol for transport, bind to retinol binding protein, transported to different cells for use - interconvertible: Retinol can be converted to retinal in the RPE (retinal pigmented epithelium), can get converted to retinoic acid in different cells

Answer 12

- High doses of synthetic retinol are toxic (50,000 IU/day or more) but if getting carotenoids from diet, you can control how much of the carotenoid is converted - Basically impossible to have Vitamin A toxicity from food sources

Answer 13

Vitamin D3 to 25-hydroxyvitamin D3 to 1alpha25-dihydroxy vitamin D3

Answer 14

- Balance of catabolic and anabolic reactions w/in the body | - balance btwn food nutrient availability, nutrient utilization, and nutrient storage

Answer 15

- It can be both - If the cell has too much glucose then it will store it if it is a hepatocyte and then prob will utilize some of it for oxidation

Answer 16

- chemical form of a fuel | - fats, carbs, and proteins (indirectly) help in prod of chemical fuel (ATP),

Answer 17

- Hormonal signals from the endocrine pancreas (insulin & glucagon) - Other hormones that help maintain metabolic homeostasis: epinephrine (comes from adrenal medulla), incretins (to some extent. Through insulin and glucagon will link the insulin glucagon pathway), cortisol (from the cortex)

Answer 18

- How much nutrient is present in blood | - Insulin and glucagon signals the cells about the nutrient levels in blood

Answer 19

- Stimulate - Parasympathetic - is highly activated during fed state (Vagus, rest and digest) - Sympathetic - is your fasting state, uses Epinephrine

Answer 20

○ It is an anabolic state and Glycogenesis (glucose to glycogen), protein synthesis (AA to protein), lipogenesis (glucose to FA, the excess glucose is converted and stored as fat) is occurring

Answer 21

- After liver makes fat it has store it in other areas so it mobilizes it out via VLDL - In order to maintain homeostasis, the triglycerides are broken down and the FA are put into VLDL which will dump the FA into the tissue which will then be formed back into triglycerides

Answer 22

○ They are using up the blood glucose immediately also via oxidation and they are storing the excess into glycogen - Protein synthesis is happening, excess AA are used for protein synthesis - Insulin because it is an anabolic hormone. All anabolic cycles are on in the fed state so that makes sense

Answer 23

- In the liver: glycogenesis & lipogenesis - In the muscles: glycogenesis, oxidation of glucose (glycolysis, TCA, ETC), and protein synthesis - Adipocyte - storage of FA into triglycerides

Answer 24

- glycogen is being broken down and glucose is being released into the bloodstream by the Liver - FA are being released from adipocyte (Lipolysis-fat mobilization of stored fat into the blood in form of FA to be used) - The muscle is releasing AA into the blood to travel to the liver to make glucose through gluconeogenesis - To maintain an adequate level of nutrients in the blood so that all other cells can get the nutrients from the blood and produce energy for survival - Catabolic - glucagon: primary one released from pancreatic alpha cells

Answer 25

- In the liver: glucagon stimulates gluconeogenesis and glycogenolysis - In the muscle: glucagon is doing nothing bc it doesn’t have glucagon receptors. There is no glucagon, but glycogenolysis does happen in the muscle. So what activates the glycogen phosphorylase there? High levels of AMP - Adipose is doing mobilization

Answer 26

- Mature insulin is 2 chains (alpha and beta chain or A or B chain) - Proinsulin are 3 peptides (a, b, & c chain) - Maturation removes the C chain

Answer 27

- No, before proinsulin there is a pre-proinsulin which undergoes post translational modifications btwn the ER and the golgi - It is released as a single peptide at the N terminal end and this happens in the ER so a pre-pro converts into the pro - in the storage vesicles, proinsulin gets packaged into vesicles and released from the golgi into the cytoplasm of the beta cells and the cells will store them and the secretory vesicles are packed w/ a protease enzyme, while in the vesicles the protease cleaves the C peptide out and converts proinsulin into mature insulin in the vesicles, so the vesicles are now storing C peptide and mature insulin.

Answer 28

- High ratio of ATP caused by glucose coming in going through glycolysis, TCA, ETC to make a lot of ATP and so it leads to ATP build up --the ATP sensitive K+ channels close which leads to depolarization and that will open up the calcium channels and the calcium then helps the cell exocytose insulin and c peptide into the blood from the cell

Answer 29

- It is a marker/measure of the endogenous insulin that the pts pancreas is releasing - C peptide has a longer half life; Insulin is degraded very quickly so its very hard to catch endogenous insulin - Yes, if you have high C peptide we can say that a large amount of the pts beta cells are working in the pancreas

Answer 30

- First phase - post prandial insulin so when you eat, the insulin spike is the first phase - Second phase: helps maintain normal glycemia; After the post prandial spike of the first phase, it doesn’t remain elevated forever, it will come down btwn the basal and first phase and that will help maintain the normal glycemia and keep everything balanced - Basal level: the sugar level. 5mmol/microliter is your homeostatic sugar level so at that 5mmol the basal level of insulin is always there. The basal level of insulin prevents too much mobilization of fats and glycogen. So prevents excess lipolysis & glycogenolysis in order to maintain the stores.

Answer 31

- protein hormone so itll be a gene product. - Prepro is much longer (120 AA) vs the mature one which is 29 AA; The mature is folded one & prepro is the straight one - If you have a glucose level below 5 mmol/liter that is a stimulus for glucagon height and when glucose is greater than 5 mmol that inhibits glucagon synthesis - greater than 5 mmol will stimulate insulin and inhibit glucagon and less than is going to increase glucagon and decrease insulin

Answer 32

- there is always a ratio of glucagon to insulin; so even when sugar is above 5 mmol there will be some glucagon secretion - insulin to glucagon ratio will be increased bc high carb spike in insulin dip in glucagon - if there are high amounts of AA in the blood following a protein meal that is a stimulus for insulin to be released bc it is getting the cells ready for protein synthesis. So there will be a spike in insulin, - glucagon will increase bc you have less glucose in blood and that is a stimulus to the alpha cells to secrete more glucagon. So the insulin glucagon ratio will be low bc glucagon is prob higher and stays higher for a longer time than insulin. Insulin will spike a little and then dip; Insulin stimulates protein synthesis. So therefore high AA levels is a stimulation to the beta cells to release insulin, but if you compare the insulin release when the beta cells are stimulated by high glucose increase vs the AA increase, there is a difference, the level will be less than the glucose stimulation

Answer 33

- liver | - Glycogenolysis and gluconeogenesis

Answer 34

- skeletal muscle | - Go into liver and make glucose via gluconeogenesis

Answer 35

- Liver, when fasting there is still glucose in the blood bc the liver is working hard to keep glucose at the homeostasic level. - Glucose and Ketones (used in extreme starvation)

Answer 36

- Fat. - Adipose: during extreme starvation, adipose tissue is doing a lot of mobilization of fats into FA and glycerol in the blood, - The liver: FA get into the liver, get oxidized, and the liver is taking up a lot of fats to make a lot of AcetylCoA. The liver is using some Acetyl CoA for its own TCA/ETC and the abundant ones are converted into ketones, released out in blood and gets to the brain. - Ketoacidosis: This is when someone who hasn’t eaten for a long time will faint

Answer 37

- glucagon

Answer 38

- A glucagon binds to its GPCR (G alpha S) which is a plasma membrane bound receptor. Activates AC which breaks ATP to cAMP and that activates PKA which will recruit other kinases and those kinases are going to phosphorylate and activate diff rate limiting enzymes involved in the diff metabolic cycles that are turned up by glucagon - PKA: has transcriptional regulation and activates CREB which binds to CRE sections of the DNA and activates the transcription of PEPCK - also inhibits the transcription of PFK-1 (rate limiting enzyme of glycolysis) which leads to inhibition of transcription of pyruvate kinase so it stops glycolysis and increases gluconeogenesis

Answer 39

(phosphoenol pyruvate carboxykinase) this is a gluconeogenesis enzyme, it is one of those bypass steps of gluconeogenesis, so PEP cannot go back in the other way so it has to take this bypass step and this is the bypass enzyme.

Answer 40

- Glycogen phosphorylase - this enzyme is phosphorylated and it is activated by a downstream kinase from PKA

Answer 41

- Insulin binds the extracellular α domain of the insulin receptor tyrosine kinase--> receptor dimerizes--> transmembrane β domains auto-phosphorylate eachother--> IRS (insulin receptor substrate) is recruited to the β domains and are phosphorylated--> PI3K is phosphorylated/activated---> convers PIP2 to PIP3--> Increases PIP3 concentration activates PDK1--> Phosphorylates/activates AKT--> goes on to do a number of things

Answer 42

- AKT recruits GLUT4 transporter-containing vessicles to the cellular membrane by inhibiting AS160 which allows for an increase in expression of GLUT4 on the cellular membrane so glucose can now enter the cytoplasm of muscle and adipose cells from the blood. - also phosphorylates/inhibits GSK3 which is always acting to inhibit glycogen synthase glycogen synthesis can now occur. - activates mTOR pathway which activates SREBP and releases it from the ER,it translocates to the nucleus, and acts as a transcription factor for the genes responsible for fatty acid synthesis. - Note that a lot of the actions that occur due to the binding of insulin will result in activation by DEPHOSPHORYLATION.

Answer 43

- inhibit the transport of GLUT4 vessicles to the membrane

Answer 44

- She would have increased insulin levels. - Poor diet and sedentary lifestyle result in low energy demands, low energy expenditure, and increased storage of glucose in adipose tissue.

Answer 45

- stuck in a catabolic state and is in a state of starvation - He would have increased levels of glucagon by breaking down muscle to obtain protein for gluconeogenesis and ketone production and breaking down fat due to stress-induced epinephrine in blood circulation.

Answer 46

- It can be disrupted by prolonged periods of anabolism/catabolism because any prolonged/chronic state causes stress on the body and can cause a sympathetic response to protect vital organs such as the brain and heart. - The fatty acids generated by this stress response used by the heart; breakdown of protein will contribute to ketone production which can be used by the brain as fuel. - If we subject our body to a prolonged/chronic state of one or the other metabolic states (either catabolic or anabolic), homeostasis will be disrupted resulting in starvation or obesity.

Answer 47

- released by the hypothalamus, - inhibits orexigenic peptides (AgRP and NPY) and increases production of anorexigenic peptides (α-MSH and CART)--> turns down appetite so you don't want to eat. - more adipose tissue you have, the more Leptin you produce --> more orexigenic peptide inhibition and more anorexigenic peptide stimulation--> will hopefully decrease appetite--> will hopefully make her eat less/lose some of her fat stores. - Less adipose/fat--> less leptin production--> less orexigenic peptide inhibition and less anorexigenic peptide stimulation--> will increase appetite--> will hopefully make him eat more/replace energy stores as a result.

Answer 48

- She is becoming leptin resistant so the leptin receptors in the hypothalamus are not responding adequately and she is not having satiety occur in the food-inhibiting center. - Now she is more prone to over-eat which will feed into the vicious cycle of more fat deposition--> more leptin--> more desensitization of leptin receptors--> still hungry--> eat more--> more fat deposition---> repeat.

Answer 49

- produced by the adipose tissue and functions to promote insulin sensitivity. - When adipose tissue is low, adiponectin is increased--> increases the body's ability to respond to insulin levels--> increasing effectiveness of glucose intake--> increase glucose storage/fat deposition - When adipose tissue is high, adiponectin is decreased--> decreases the body's ability to respond to insulin levels--> decreasing effectiveness of glucose intake--> decrease glucose storage/fat deposition

Answer 50

- CCK: comes from I cells in the duodenum during the intestinal phase of digestion; It helps stimulate satiety by inhibiting orexigenic peptides (food-inducing) and increasing anorexigenic peptides (food-inhibiting), It does this because the meal has reached the intestines and there is no need to continue eating. - PYY: Does the same thing as CCK but is produced in the ilium and colon, Tells the hypothalamus that food is in the intestines and colon so there is no need to eat a meal while you are currently digesting a meal. - Ghrelin- is the opposite of lectin; increased during fasting to tell your brain that it is hungry and needs a meal decreased in patients with obesity and increased in patients consuming low calorie diets (also low in patients who are exercising)

Answer 51

- The apple (central adipose tissue) is worse due to the increased risks that come along with abdominal fat. - Abdominal fat is in close proximity to the liver and fatty-acid breakdown products of the adipose tissue can easily enter the portal circulation. The free fatty acids will stimulate gluconeogenesis/glucose production at the level of the liver--> will stimulate the pancreas to produce more insulin--> chronically desensitizes insulin receptors--> insulin resistance - chronic metabolic imbalance induces a state of stress and epinephrine release which has more of a lipogenic effect on centralized fat than it does on peripheral fat so under stress, abdominal fat will break down a lot more. Additionally, its' location will allow for easy entrance of free fatty acids into the portal circulation.

Answer 52

- High glucose levels despite high C peptide levels (adequate insulin production by the pancreas) indicates insulin resistant Type 2 Diabetes. - AKT pathway including AS160 is likely not working which means that GLUT4-containing vessicles are not being released or expressed on the cellular membrane despite insulin binding. This decreases the amount of glucose being taken up into muscle and adipose cells. Hyperglycemia (increased glucose in the blood) is the result. - Even though AS160 pathway is not working the SREBP is still being activated by AKT due to bound insulin, causing increased fatty acid synthesis. High insulin levels--> increased SREBP activity--> increased fatty acid synthesis--> hyperlipidemia - The protein synthesis pathway still works and is accelerated by insulin levels. - Type 1: There is no insulin produciton--> with no insulin signal, there is decreased fatty acid and protein synthesis--> these patients are thin; Type 2: There IS insulin produciton--> the fatty acid and protein synthesis pathways are still able to respond to insulin--> increased fat and muscle density - Gluconeogenesis is upregulated in diabetic patients despite high blood glucose levels due to metabolic dysregulation (one of the most important things that metformin does as a treatment is decrease gluconeogenesis)

Answer 53

- ® 2 pyruvtaes from 1 glucose because pyruvate is a 3 carbon structure and glucose is a 6 carbon structure - Insulin and glucagon - PFK 1: Insulin will activate PFK2; insulin with dephosphorylate PFK2 making it a kinase and PFK2 will make more Fructose-2,6-bisphophate. And if there is high amount of F-2,6-BP that will activate PFK1 to make more fructose-1,6-bisphopshate. ; indirect regulation but it is still regulation - High levels of glucagon will phosphorylate PFK2 which makes it a phosphatase and will take off the phosphate from 6th position of F-2,6-BP and then it will down regulate PFK1 - pyruvate, ATP( 2), NADH (2)

Answer 54

- Limits too much production of G6p, it prevents cells from absorbing too much glucose

Answer 55

- regulated by insulin and glucagon | - Insulin will activate and glucagon will de-activate

Answer 56

- PDH- pyruvate dehydrogenase - It is an enzyme complex: E1, E2, E3 - Co enzymes: Vit B 1 (thymine)--most important because E1 is dependent on it; Vit B2--riboflavin, lives in form FAD+/FMN so it is needed to make FADH2; Vit B 3- niacin, because glycolysis produces NADPH and will require niacin because it lives in form of NAD+ - Down regulate PDH because PDH is making acetyl CoA so if you already have it you wouldn't want to make more - No, acetyl CoA cannot be made back into pyruvate--cannot go from fat to glucose directly

Answer 57

- Dehydrogenases will be down regulated because they make NADH and you already have too much so you want to prevent making more - Will turn off a lot of TCA enzymes, PDH, and GAP-DH in glycolysis

Answer 58

- Iso citrate dehydrogenase, Citrate synthase, Alpha ketogluterate dehydrogenase - Producing 3 NADH and 1 FADH2 and a GTP that can be converted to ATP - Electron carriers for the ETC

Answer 59

- NADH dehydrogenase- it converts NADH to NAD+, this is redox reaction; NADH is giving up 2 electrons as hydride ions and oxidizes to NAD+ - Called NADH co-enzyme Q oxidoreductase: because it is redox reaction occurring - FMN: Also known as vit B2--riboflavin; will grab the electrons and give it to Fe-S and then give the electrons to the main acceptor (Co-enzyme Q) - Lipid derivative that moves freely in the mitochondria and is not attached to membrane; Acts as electron carrier and will carry (2) electrons to complex III; it waits for another one, but if another one doesn’t come then it becomes semi-quinone which is a free radical

Answer 60

- Succinate dehydrogenase is attached to FADH2 and FADH2 will pass electrons to the Iron-sulfur complex to Co-Q - Succinate dehydrogenase is also in TCA enzyme and is shared by ETC; succinate dehydrogenase is what turns FAD into FADH2 in the TCA then will immediately take the FADH2 to complex 2 of the ETC - Carrier between complex II and III is Co-Q

Answer 61

○ Contributes to proton gradient like complex I (complex II does not) ○ Complex III has complex cytochrome b-C1 □ Similarity between cytochrome and hemoglobin is that they both have heme but the heme is different in that cytochrome heme is Fe+3 and hemoglobin heme is Fe+2

Answer 62

- Helps to recycle one electron from co-enzyme Q through cytochrome B and then back to co-enzyme Q - co enzyme Q from 1 is brining in 2 electrons and cytochrome C between complex 3 and 4 can carry only 1 electron, so the extra electron has to go through a cycle and come back again so that it can be loaded into cytochrome C. So Co-Q coming from complex 2 or 3 will donate 1 electron that will go through Fe-S and will keep going through cytochrome C1 and then cytochrome C which will bring it to complex 4; the other electron will go down to cytochrome b (there are two types of cytochrome b, bH and bL) and be held at the Q site by oxidized co-enzyme making it semi-Q (as known as co-Q H). When the next CoQ goes through the same cycle of donating 1 electron to go through cytochrome C and the other to the Q cite making the co-Q H into co-Q H2. - supplementation of Co-Q10 when on statins is important, because if you deplete the amount of cholesterol with long term use of a statin then you deplete co-Q10 and the effect will be most pronounced in muscles because of high energy demand

Answer 63

- takes electrons from cytochrome C and the electrons will go to Oxygen which will be reduced to water - AAC and has copper.

Answer 64

- there will be high NADH in the blood because NADH will not be able to donate its electron and will therefore stay in reduced form as NADH. - Everything beyond the complex will remain oxidized and everything before the complex will remain reduced; All CoQ will remain oxidized - No ATP will be produced; because there will not be any proton pumping - Lactate dehydrogenase will be activated; High NADH built up in mito which shuts down all dehydrogenases--this causes the TCA to shut down. To compensate for ATP production glycolysis will accelerate to make more ATP--this leads to an increase in pyruvate. In order to prevent a build up of pyruvate that would stop glycolysis and therefore ATP production the pyruvate will be converted to lactate. Over compensation will therefore lead to lactic acidosis.

Answer 65

- Complex 5 with the ATP anythase - Build up of proton gradient on outside - there is proton build up in intermembrane space, so then the protons will flow down their gradient in complex 5 (proton channel). The proton channel is linked to an F1 portion and as the protons flow down their gradient it will combine ADP with Pi making ATP.

Answer 66

- Oxidation of NADH ; every time two electrons moves from NADH to the next complex the energy that is released will pump out four protons from that complex - So at complex 1; from complex 1 to 3; from complex 3 to 4 only one electron is moved at a time so only 2 hydrogen will be pumped out at a time - FADH2 comes in at complex 2 and complex 2 does not do proton pumping.

Answer 67

- It will uncouple ETC from ATP synthesis - The proton gradient is diffused by the un-coupler so there is no more proton gradient and therefore the protons wont come back through complex 5 so ATP will not be produced - It will speed up TCA in order to make more NADH and FADH2 to try and speed up ETC in an effort to make ATP. Electrons are going to oxygen fine but because of presence of un- coupler and absence of proton gradient we are no longer making ATP. Increase in TCA will increase amount of NADH which will transport more electrons to oxygen leading to an increase in oxygen consumption. - Increased basal metabolic rate because at resting state you will have increase in oxygen consumption but less ATP production - When the electrons are being transferred you are producing energy which is normally used to pump out protons, however, since there is not a proton gradient we are not pumping out the protons so the energy comes out as heat and presents as hyperthermia.

Answer 68

- Fructose and galactose | - sucrose comes naturally from fruits (fructose and glucose) lactose comes from milk (galactose and glucose)

Answer 69

- Fructose will be phosphorylated into fructose-1-phosphate by fructokinase (this happens in order to lock it in cell, if not it can just leave the cell through the glut 5 transporter) and then that gets cleaved into DHAP (di-hydroxy acetone phosphate) and glyceraldehyde by aldelase B (also called F1P aldelase). Then the glyceraldehyde gets phosphorylated to glyceraldehyde 3 phosphate (GAP) by triose kinase. - DHAP is also seen in glycolysis, and is a glycolysis intermediate so it will go back into glycolysis immediately, GAP is also an intermediate in glycolysi, Once GAP and DHAP are formed and put into glycolysis they will continue and make pyruvate - Can go to lactate or to acetyl CoA into the TCA to make more fats - There is no feedback inhibition with fructose. So basically, nothing gets blocked at point number one with fructose kinase. So when there is excess fructose you continue to go down same pathway in excess. - no way to inhibit the pathway like we can with glucose since hexokinase is inhibited with product inhibition.

Answer 70

- we will have a lot of pyruvate forming a lot of Acetyl CoA which will supply a lot of carbohydrate carbons to make fat from because we will form acetyl CoA it will go into the TCA, become citrate, and as citrate can get out of the mitochondria, it will get into cytoplasm become oxaloacetate and acetyl CoA and then Acetyl CoA can be used to make fatty acids and cholesterol. We will talk about this more on Monday when we get into lipids, but we can see some fat build up in the liver with excess fructose. Therefore, excess fructose is a risk factor for fatty liver. - lead to increase in lactate because if there is too much pyruvate it will start being shunted into lactate - if there is enough fructose then the liver cells will become exhausted and be unable to make ATP because they run out of phosphates, which will affect the functioning of the hepatocytes - Since pyruvate can also be turned back into glucose with gluconeogenesis then it will cause a higher amount of G6P which can go down pentose phosphate pathway which will form more NADPH and 5-carbon sugars and that will contribute to increase in uric acid - High fructose corn syrup-- some experts have said that high fructose corn syrup may be one of the contributing factors to the obesity epidemic and fatty liver epidemic in western countries.

Answer 71

- F1P aldolase cleaves fructose to glyceraldehyde to GAP and then to DHAP so if this is deficient the large amount of fructose being taken in would not be able to be utilized in glycolysis

Answer 72

No, because then all peripheral cells will have difficulty keeping glucose in the so that cannot be the problem here. It will be a much bigger problem and probably not a viable mutation.

Answer 73

• Glycogen is made up of a lot glucose molecules. Glucose is a monosaccharide and glycogen is a polysaccharide

Answer 74

- Glycogen is stored in the liver and muscle but more in muscle. - Muscle glycogen is for energy and liver glycogen maintains blood glucose homeostasis. - It is highly Branched - alpha 1-6 (at the branch point ) and 1-4 glycosidic bonds (main growing chain) - one reducing end and it is where the anomeric carbon( carbon 1) binds to glycogenin the protein that starts glycogen synthesis. - branches or the ends of the branches are non-reducing ends so they don’t have the anomeric OH available which means the exposed end of the last glucose is the 4th carbon. Having non-reducing ends is good because the enzyme glycogen phosphorylase acts at the non-reducing ends and breaks the glycogen to glucose.

Answer 75

- Glucose is converted to G6P by glucokinase or hexose kinase then it is turned into G1P by phosphoglucomutase. UDP glucose phosphorylase then converts UTP to UDP and adds it to the G1P to give UDP glucose which is ready to form glycogen. We also have a glycogen primer, glycogenin which is already made by the cell. Glycogen synthase will add 4 UDG glucose to the non-reducing end of the glycogenin and facilitate the formation of alpha 1,4 bonds. - When we reach about 11 glucose units in our growing glycogen chain, then the debranching enzyme comes in and cuts out 6-8 units and attach it as a branch forming an alpha 1,6 bond. The process is repeated after about every 10 units

Answer 76

- has a high energy bond like ATP so it is energy producing. When you convert the UTP to UDP you are hydrolyzing a highly phosphate bond which leads the release of energy.

Answer 77

- anabolic enzyme so an anabolic hormone like insulin can stimulate it. - Insulin will dephosphorylate glycogen synthase which activates it and glycogen phosphorylase which inactivates it. This is because synthesis and degradation cannot go on at the same time.

Answer 78

- no because it involves different enzymes and they are called futile cycle because if the cell is doing both at the same time it will die - Glucagon will phosphorylate glycogen phosphorylase causing activation and glycogen synthase causing inactivation - glycogen phosphorylase will change glycogen to G1P. There is a debranching enzyme involved which comes in and cleaves the alpha 1,6 bonds because glycogen phosphorylase cannot cleave it. - Muscles don’t have glucose 6 phosphatase so when glycogen is degrading in muscles it will go to G6P and then go into glycolysis or pentose phosphate pathway route. It is also a high energy demand tissue - In the liver the G6P will do some glycolysis but most of it will be converted to glucose so it can be released into blood because it has the glucose-6-phosphotase which changes G6P back into glucose

Answer 79

- due to deficiency of G6P phosphatase, so liver wont be able to release glucose into the blood causing G6P to accumulate in the liver which will lead to low glucose. - Fatty acids leading to ketone bodies and high fatty acid in the blood. - There is G6P build which can go glycolysis, so we will have high pyruvate and then high lactate formation. - The G6P can back to glycogen synthesis and so we will have glycogen accumulation leading to the hepatomegaly.

Answer 80

- gycogen phosphorylase deficiency | - will have glycogen accumulation and not G6P and therefore there wont be lactate formation.

Answer 81

- McArdle affects muscle so would have a presentation of muscle weakness/myalgia - pompe is a glucosidase deficiency which is seen as cardiomyopathy and skeletal muscle damage, also very serious in infantile.

Answer 82

- No because glycolysis has 3 irreversible reactions which are mediated by enzymes that are highly regulated and so you cannot go back to those but you need to bypass them and you have a couple of new enzymes coming in

Answer 83

- pyruvate to oxaloacetate vy pyruvate carboxylase and biotin( B7) which requires ATP. - The formed oxaloacetate will form phosphoenolpyruvate which is a glycolysis intermediate using enzyme PEP carboxykinase - glucagon will activate PEP carboxykinase by increasing its expression and Acetyl CoA will also activate - Once we get to PEP we start to do opposite of glycolysis making 2-phosphoglycerate to 3-phosphoglycerate to 1-3 bisphosphoglycerate,then 2 glyceraldehyde 3- phosphate, and DAP, and both can be converted back to fructose 1, 6 bisphosphate - PFK-1 is an irreversible step so fructose 1,6 bisphosphate to fructose 6 phosphate through fructose 1,6 bisphosphate, then fructose-6-phosphate it will form glucose -6-phosphate by isomerization - G6P goes to glucose through the use of glucose -6-phosphotase

Answer 84

glucagon will phosphorylate and activate enzyme

Answer 85

only present in the liver

Answer 86

- gluconeogenesis is making glucose from non-carbohydrate sources specifically from AA in skeletal muscle including, alanine, serine, creonine, tryptophan

Answer 87

- Glycemic index: standard amount of available carbs and - Glycemic load: glycemic index times the actual amount of carbs in a serving - glycemic load

Answer 88

- vegetables, oatmeal, water(LOL), celery

Answer 89

- donuts, white bread, white pasta, processed food - If the starch looks white it is probably a higher glycemic load, if the starch looks pigmented it is probably a lower glycemic load because more colorful food is processed

Answer 90

- Because a lot of sugar in a liquid makes the liquid thick and viscous which will start to cause circulation dysfunction, first in the small vessels - Typical body range is 70-100

Answer 91

- insulin - High - yes, become hypoglycemic

Answer 92

- processing fiber, fat, protein - Removing the fiber content, increase glycemic load because it is a non-starch polysaccharide that is not digestible by human enzymes

Answer 93

- Big molecule that can obstruct smaller molecules - Fiber can uptake and trap other sugar molecules which improves insulin sensitivity, and lipid effects - brown flour lost its fiber so it is not trapping the sugar, so you can see a high glycemic spikes with processed grains - White grain has gotten rid of the bran and some of the germ which is unfortunate because it loses some of the vitamins which have to be added back (fortified) - Soluble: dissolves a bit in water and makes a gel like substance and changes viscosity (psyllium like meta-mucil in supplemental form, beta-glucan which is in cognac roots) vs Insoluble: Remains as particles dissolving - Oatmeal, barley, mushrooms - Insoluble fibers good for constipation

Answer 94

- Decreases glycemic index, absorb fats so it has to metabolize more than one thing at a time so it cant concentrate on glucose; if you have fat in there it will occupy its time to digest fat - Combining carbs with fat or especially protein can slow down the absorption (for diabetic patients)