Lec 6: Metabolism Flashcards
Metabolism
the chemical processes that occur within a living organism in order to maintain life
Digestion
the process of breaking down food to its smallest components so that it can be absorbed in the intestine
Absorption
the transport of nutrients from the intestine into the blood or lymph system
Carbohydrate classification (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
Key enzymes in carb metabolism (3 areas, 5 enzymes)
- Mouth- salivary amylase from salivary glands
*breaks down starch - Duodenum- pancreatic amylase from pancreatic juice
*breaks down starch - Small intestine- maltase, sucrase, lactase from brush border
*breaks down maltose, sucrose and lactose
Carb digestion in mouth
-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
Carb digetsion in stomach
-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
Carb digestion and absorption in small intestine
-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
Blood glucose regulation
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
Insulin
-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
Hyperinsulinemic-euglycemic clamp and insulin sensitivity
-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
Hyperinsulinemic-euglycemic clamp process
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)
Diabetes
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)
Glycated hemoglobin (HbA1C)
-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)
HbA1C diagnosis cutoff values
Not at risk/healthy= 5.5-5.7%
Prediabetes= 6-6.4%
Diabetes= > or = 6.5%
Carbohydrate uptake at skeletal muscle process (3)
- Glucose passes through sarcolemmal membrane from systemic circulation through GLUT4, paired with insulin
- Goes through glycolysis and produces pyruvate
- Pyruvate enters TCA cycle and ETC to produce energy
Mitochondria structure
Inside the mito matrix:
-Outer mitochondrial membrane
-Intermembrane space
-Inner mitochondrial membrane (has folds called cristae that contain ETC complexes to produce energy)
Cristae
ETC complexes reside in cristae and cristae density increases with exercise training
*more trained= more ETC complexes and mito adaptations
TCA cycle
-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
ETC
-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)
Undigested carbs
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
Amino acid metabolism
integrated across multiple tissues
-liver
-stomach
-small intestine
*basis of protein building
Protein structure
AA= carboxyl group and amino group (N2) and peptide bond
-peptide bonds broken down via hydrolysis reactions into polypeptide, tripeptide, dipeptide, monopeptide (smaller components)
Chemical digestion of protein
-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
Enzymes in protein breakdown
- Pepsin- stomach
- Trypsin
- Chymotrypsin
- Carboxypeptidase
- Elastase
*rest is from small intestine
Amino acid absorption
-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
Amino acid metabolism
-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
Transamination
-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
First-pass splanchnic extraction
-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)
Postprandial protein handling “you are what you ate”
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
Branched chain amino acid metabolism
-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
Deanimation
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
The liver a.a. involvement
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
The large intestine a.a. involvement
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
Fatty acid metabolism key enzymes (2)
- Lingual lipase- mouth (salivary glands)
- Pancreatic lipase- duodenom (pancreatic juice)
Fat digestion in the mouth
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
Fat digestion in the stomach
Lipase continues to breakdown triglycerides in the stomach but this hydrolysis is slow
Fat digestion at the duodenum
-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
Fat packaging in epithelial cells of the intestine
-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
Fatty acid uptake at skeletal muscle
-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
Beta-oxidation activation steps
-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
Beta-oxidation products
-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
