Lec 6: Metabolism

Question 1

Metabolism

Answer 1

the chemical processes that occur within a living organism in order to maintain life

Question 2

Digestion

Answer 2

the process of breaking down food to its smallest components so that it can be absorbed in the intestine

Question 3

Absorption

Answer 3

the transport of nutrients from the intestine into the blood or lymph system

Question 4

Carbohydrate classification (4)

Answer 4

Carbs broken down into:
1. Monosaccaride (1 sugar molecule)
-glucose, fructose, galactose
2. Disaccharide (2 sugar molecules)
-sucrose, lactose, maltose
3. Oligosaccharide (3-10 sugar molecules)
-Raffinose, stachyose
4. Polysaccharide (10+ sugar molecules)
-starch, glycogen, cellulose

Question 5

Key enzymes in carb metabolism (3 areas, 5 enzymes)

Answer 5

1. Mouth- salivary amylase from salivary glands
   *breaks down starch
2. Duodenum- pancreatic amylase from pancreatic juice
   *breaks down starch
3. Small intestine- maltase, sucrase, lactase from brush border
   *breaks down maltose, sucrose and lactose

Question 6

Carb digestion in mouth

Answer 6

-Digestion begins in the mouth
-Saliva secreted from parotid glands, sublingual glands and submandibular glands
-Chewing food mixes in saliva and increases surface area so amylase can start breaking down glucose chains in starches
-Products of starch breakdown= disaccharides like maltose and monosaccharides like glucose

Question 7

Carb digetsion in stomach

Answer 7

-food is swallowed and arrives at stomach, amylase activity decreases due to stomach acidic environment
-Carb digestion still occurs (HCl) but at much slower rate
-Chyme (semifluid mass of partly digested food) is expelled by stomach into duodenum

Question 8

Carb digestion and absorption in small intestine

Answer 8

-Disaccharides (lactose, maltose, sucrose) broken down by their enzymes into absorbable monosaccharides

-amylase is secreted in pancreatic juice to further break down starches into smaller glucose units in the duodenum
-at the small intestine, disaccharides and small polysaccharides are digested by specific enzymes located in the brush borders of epithelial cells

-glucose and galactose absorbed through SGLT and then GLUT2
-fructose absorbed through GLUT5 and then GLUT2
-all enter bloodstream (hepatic portal vein to liver)
*most absorption happens at duodenum and jejunum of small intestine, breakdown almost complete at ilieum

Question 9

Blood glucose regulation

Answer 9

High blood sugar:
-insulin released from beta cells in pancreas
-stimulates glycogen synthesis into liver and tissues
-lowers blood glucose

Low blood sugar:
-glucagon released from alpha cells in pancreas
-stimulates glycogen breakdown (glycogenolysis)minto glucose
-raises blood glucose

Question 10

Insulin

Answer 10

-Hormone that acts to increase cell uptake of glucose from the blood
-When blood glucose increases see an increase in beta cell insulin release, which increases blood insulin and therefore activation of insulin receptor mediated signalling leading to increased tissue glucose uptake and restoration of blood glucose

Question 11

Hyperinsulinemic-euglycemic clamp and insulin sensitivity

Answer 11

-Gold standard method for measuring insulin sensitivity
-Insulin sensitivity refers to how much of an increase in tissue blood glucose uptake occurs for a given increase in blood insulin
-Increased insulin sensitivity= rate of glucose removal from blood is increased at a given blood insulin conc. *more uptake
-Decreased insulin sensitivity= rate of glucose removal from blood is decreased at a given blood insulin conc. *less uptake

Question 12

Hyperinsulinemic-euglycemic clamp process

Answer 12

Step 1: infuse insulin to elevate blood insulin, and it is maintained at a constant elevated conc.
-increasing insulin will increase the uptake of glucose in tissues so there’s an increase in outflow of blood glucose meaning blood glucose decreases

Step 2: infuse glucose to increase blood glucose
-glucose infusion rate (inflow) is then matched to insulin induced glucose uptake (outflow) so that blood glucose becomes stable *clamped

*measures at what level glucose infusion is needed to match insulin related uptake (increased insulin sensitivity= higher glucose infusion rate needed to match outflow/uptake, higher at the clamp/plateaus higher)

Question 13

Diabetes

Answer 13

Type 1= insulin deficiency as pancreatic beta cells are unable to produce insulin

Type 2= pancreatic beta cells can still produce some insulin but the level is insufficient to compensate for insulin resistance resulting in hyperglycemia

Type 2 diabetes demonstrate impaired insulin-stimulated glucose uptake into tissues and fasting blood glucose concs. are often very high

Prediabetes refers to elevated fasting glucose or an HbA1C of 6-6.4% (prediabeteic= increased risk of developing type 2 diabetes)

Question 14

Glycated hemoglobin (HbA1C)

Answer 14

-Glucose in the bloodstream can bind to hemoglobin in RBCs forming glycated hemoglobin
-Glycated hemoglobin (HbA1C) tests are used to assist the diagnosis of diabetes
-HbA1C tests reflect average plasma glucose over previous 2-3 months (more reflective of lifestyle than single blood sample)

Question 15

HbA1C diagnosis cutoff values

Answer 15

Not at risk/healthy= 5.5-5.7%
Prediabetes= 6-6.4%
Diabetes= > or = 6.5%

Question 16

Carbohydrate uptake at skeletal muscle process (3)

Answer 16

1. Glucose passes through sarcolemmal membrane from systemic circulation through GLUT4, paired with insulin
2. Goes through glycolysis and produces pyruvate
3. Pyruvate enters TCA cycle and ETC to produce energy

Question 17

Mitochondria structure

Answer 17

Inside the mito matrix:
-Outer mitochondrial membrane
-Intermembrane space
-Inner mitochondrial membrane (has folds called cristae that contain ETC complexes to produce energy)

Question 18

Cristae

Answer 18

ETC complexes reside in cristae and cristae density increases with exercise training
*more trained= more ETC complexes and mito adaptations

Question 19

TCA cycle

Answer 19

-In mito matrix
-Pyruvate broken down into acetyl-CoA by PDH
-Citrate synthase breaks down acetyl-CoA
-Produces NADH and FADH2 (with ATP reactions as well), which enter ETC to produce more ATP

Question 20

ETC

Answer 20

-located on cristae on inner mitochondrial membrane
-4 complexes
-NADH and FADH2 enter
-Paired with O2, creates H+ gradient into intermembrane space and back into matrix
-This gradient drives proton motor force/ATP synthase to poroduce ATP

*foods converted to energy, using O2, through ETC complexes (H+ gradient drives ATP synthase)

Question 21

Undigested carbs

Answer 21

Fiber is a form of dietary carb that contains cellulose
-cellulose is resistant to digestive enzymes (some cellulose excreted in feces but some of it is fermented by bacteria in the large intestine
-Peristaltic movements push undigested carbs including fibrous substances to the colon

Question 22

Amino acid metabolism

Answer 22

integrated across multiple tissues
-liver
-stomach
-small intestine
*basis of protein building

Question 23

Protein structure

Answer 23

AA= carboxyl group and amino group (N2) and peptide bond
-peptide bonds broken down via hydrolysis reactions into polypeptide, tripeptide, dipeptide, monopeptide (smaller components)

Question 24

Chemical digestion of protein

Answer 24

-Begins in the stomach
-Gastrin (hormone secreted by the stomach) increases HCl-parietal cells- and pepsinogen-chief cells- secretion
-HCl helps denature protein and increases active pepsin
(pepsinogen is the inactive form of pepsin that is activated by HCl in an acidic environment)
-Pepsin converts proteins into smaller polypeptides

Question 24

Enzymes in protein breakdown

Answer 24

1. Pepsin- stomach 2. Trypsin 3. Chymotrypsin 4. Carboxypeptidase 5. Elastase *rest is from small intestine

Question 25

Amino acid absorption

Answer 25

-The small intestine is the site of the majority of amino acid absorption -Pancreatic proteases (trypsin, chymotrypsin, carboxypeptidase, elastase), brush border enzymes and peptidases free individual amino acids

Question 26

Amino acid metabolism

Answer 26

-The liver is a central hub for amino acid metabolism -amino acids are transported to the liver via the hepatic portal vein -undergo protein synthesis, transamination and oxidation

Question 27

Transamination

Answer 27

-transfer amino acids -transanimation reactions involve the transfer of the amino group from one amino acid to a keto acid like a-ketoglutarate via aminotransferase enzymes -produce alanine, pyruvate, glutamate, a-ketoglutarate

Question 28

First-pass splanchnic extraction

Answer 28

-impacts circulating amino acid levels =the uptake and utilization of amino acids by the GI tract and liver to support turnover and metabolic processes (influence how much a.a. in protein put into excretion)

Question 29

Postprandial protein handling "you are what you ate"

Answer 29

20g casein ingestion -~55% available in systemic circulation (lose rest through first-pass splanchnic extraction) -~20% of it absorbed into skeletal muscle -~11% used for muscle protein synthesis

Question 30

Branched chain amino acid metabolism

Answer 30

-branched chain= leucine, isoleucine and valine -primarily intiated in skeletal muscle -branched chain a.a. largely bypass metabolism in splanchnic tissues like the liver so a large proportion of catabolism is initiated in skeletal muscle -can go through transanimation and deanimation -impacts numerius metabolic pathways, a.a. breakdown can help produce energy but very small amount

Question 31

Deanimation

Answer 31

During deanimation reactions the amino group is removed from the amino acid producing ammonia -Ammonia is a toxic byproduct which needs to undergo conversion to ammonium prior to urea cycle

Question 32

The liver a.a. involvement

Answer 32

The liver processes nitrogenous by-products and houses the urea cycle -Ammonia (toxic byproduct of deanimation) is transported to the liver and converted to ammonium prior to urea cycle which leads to the formation of urea -urea transported to the kidneys for excretion as urine

Question 33

The large intestine a.a. involvement

Answer 33

Remnant undigested and unabsorbed components of dietary proteins travel to the large intestine where they are metabolized by microbiota or digested by remaining proteases and peptidases

Question 34

Fatty acid metabolism key enzymes (2)

Answer 34

1. Lingual lipase- mouth (salivary glands) 2. Pancreatic lipase- duodenom (pancreatic juice)

Question 35

Fat digestion in the mouth

Answer 35

Saliva contains small amounts of lingual lipase- enzyme that splits tricglycerides into fatty acids and glycerol Triglyceride: -Saturated (no double bonds, all carbons bonded to H+) -Monounsaturated (one carbon double bond) -Polyunsaturated (2+ double carbon bonds) Hydrocarbon chain: Short chain- C4-6 Medium chain- C8-10 Long chain- C12-24

Question 36

Fat digestion in the stomach

Answer 36

Lipase continues to breakdown triglycerides in the stomach but this hydrolysis is slow

Question 37

Fat digestion at the duodenum

Answer 37

-When chyme enters the duodenum, bile salts and pancreatic lipase are secreted into duodenum -Bile salts emulsify large lipid droplets into small lipid droplets while pancreatic lipase breaks them down into fatty acids, diacylglycerols and monoacylglycerols -Micelles are circular/disk shaped structures comprised of compounds like phospholipids and fatty acids -Micelles transport fatty acids to the villi where the contents of the micelle enter epithelial cells

Question 38

Fat packaging in epithelial cells of the intestine

Answer 38

-In epithelial cells, fatty acids are re-esterified to triglycerides which combine with cholesterol and phospholipids to form chylomicrons -Chylomicrons allow the transport of long chain fatty acids in plasma but are absorbed into the lymphatic system via lacteals prior to transport in the circulatory system -Short and medium chain fatty acids enter the epithelial cell but are not re-esterified to triglycerides -Short and medium chain fatty acids diffuse into the bloodstream where they are bound to albumin and are transported to the liver

Question 39

Fatty acid uptake at skeletal muscle

Answer 39

-When chylomicrons arrive at skeletal muscle lipoprotein lipase (LPL) breaks down triglycerides into FFA and glycerol -The contents of the chylomicrons are transported into skeletal muscle via various transporters such as CD36 and FABPPm -Short and medium chain fatty acids do not require fatty acid transport protein binding to cross the sarcolemmal membrane

Question 40

Beta-oxidation activation steps

Answer 40

-CPT-1 is the rate limiting step in long-chain fatty acid oxidation -Carnitine activates CPT-1 -Palmitoyl-CoA produced (can't enter mito), combined with carnitine and activated CPT-1 forms palmitoylcarnitine which can then enter mitochondria -CPT-2 activates conversion of palmitoylcarnitine (fatty acyl carnitine) to palmitoylCoA (fatty acyl CoA) -Fa CoA then goes through b-oxidation, increase acetyl CoA and goes through cycles to increase ATP

Question 41

Beta-oxidation products

Answer 41

-Each round of beta-oxidation removes 2 carbons from the fatty acid chain and generates acetyl-CoA -Some FADH2 and NADH are also formed -Acetyl CoA enters TCA cycle