Metabolism Flashcards
Carbs: uses in body
■ Glucose - fuel used by cells to make ATP
-Some cells use fats for energy
-Neurons and RBCs ~ entirely on glucose; neurons die quickly without glucose
■ Excess glucose converted to glycogen or fat and stored
■ Fructose and galactose converted to glucose by liver before circulation
Liver makes _% of cholesterol
85%
Lipids: uses in body
■ Help absorb fat-soluble vitamins
■ Major fuel of hepatocytes and skeletal muscle
■ Phospholipids essential in myelin sheaths and all cell membranes
■ Adipose tissue à protection, insulation, fuel storage
■ Prostaglandins à smooth muscle contraction, BP control, inflammation
■ Cholesterol stabilizes membranes; precursor of bile salts, steroid hormones
All-or-none rule
All amino acids needed must be present for protein synthesis; if not, amino acids used for energy
4 types of nitrogen compounds
1) Amino acids:
■ framework of all proteins, glycoproteins, and lipoproteins
2) Purines and pyrimidines:
■ nitrogenous bases of RNA and DNA
3) Creatine:
■ energy storage in muscle (creatine phosphate)
4) Porphyrins:
■ bind metal ions
■ essential to hemoglobin, myoglobin, and cytochromes
Nitrogen balance occurs when
■ nitrogen absorbed from the diet (mainly protein)
■ balances nitrogen lost in urine and feces
(+) nitrogen balance
■ Individuals actively synthesizing N compounds:
-need to absorb more nitrogen than they excrete
-e.g., growing children, athletes, and pregnant women
(-) nitrogen balance
■ When excretion exceeds ingestion
-Starvation or muscle wasting
7 minerals required in moderate amounts
Calcium, phosphorus, potassium, sulfur, sodium, chlorine, and magnesium
Fat-soluble vitamins
■ Vitamins A, D, E, and K:
-are absorbed primarily from the digestive tract along with lipids of micelles
-normally diffuse into cell membranes and lipids in liver and adipose tissue
Vitamin A
■ Provitamin A (Beta –carotene)
■ A structural component of rhodopsin pigment retinal; Antioxidant
-needed for scotopic (low light) vision
-Deficiency Þ night blindness
■ OD toxic signs & symptoms include:
-Headache, Chapped lips, Blurred vision, Liver toxicity, Alopecia (hair loss), Menstrual irregularities, Tinnitus (ringing in ears)
Vitamin D (calciferol)
■ Is converted to calcitriol:
-which increases rate of intestinal calcium and phosphorus absorption
Deficiencies result in:
-Osteomalacia in adults leading to weakening of the skeleton and pathologic fracture
-Rickets in children marked by poorly mineralized, soft bone
■ Common cause of deficiency is steatorrhea – a fat malabsorption syndrome
■ Toxicity:
-Brain, cardiovascular and kidney damage.
Vitamin E (tocopherol)
■ Stabilizes intracellular membranes
■ popular antioxidant
■ Needed for Hair/skin maintenance, reproductive patency
■ No reproducible, clinical signs and symptoms of overdose toxicity
Vitamin K (aquamephyton, antihemorrhagic vitamin)
■ Helps synthesize several proteins:
-including 3 clotting factors including Prothrombin
■ produced by bacteria in large intestine bowel
■ Note: Coumadin (anticoagulant) - blocks Vit. K uptake and utilization to decrease Prothrombin formation by liver and prolongs clotting times
■ overdose toxicity can lead to liver damage and anemia
Vitamin reserves
■ The body contains significant reserves of fat-soluble vitamins
■ Normal metabolism can continue several months without dietary sources
Water-soluble vitamins
■ Are components of coenzymes
■ Are rapidly exchanged between fluid in digestive tract and circulating blood:
-excess is excreted in urine
Bacterial inhabitants of intestines produce small amounts of:
■ fat-soluble vitamin K
■ some water-soluble vitamins
Vitamin C- Absorbic Acid
▪ Promotes the laying down of collagen in connective tissues – antioxidant
▪ Overdose toxicity – Gi upset
▪ Deficiency results in scurvy – a connective tissue disorder
B-complex vitamins
■ most act as coenzymes for enzymes of intermediary metabolism
■ NOTE : B6 (Pyridoxine) - is linked to sensory neuropathies in high doses with S & S including: Numbness of hands/feet, unstable gait, decreased deep tendon reflexes
■ Niacin (B3; Component of NAD+) - Low dose toxicity ® skin flush; High dose toxicity ® skin rash, liver toxicity
Metabolism
Biochemical reactions inside cells involving nutrients
■ Enzymes shift high-energy phosphate groups of ATP to other molecules (phosphorylation)
■ Phosphorylated molecules activated to perform cellular functions
Anabolism
synthesis of large molecules from small ones
■ Ex. Amino acids ➡️proteins
■ Endergonic = Energy Requiring with energy provided by ATP
Catabolism
hydrolysis of complex structures to simpler ones
■ Ex. Proteins ➡️amino acids
■ Exergonic = Releases energy used to synthesize high-energy compounds (e.g., ATP)
Cellular respiration
Catabolism of food fuels ➡️capture of energy to form ATP in cells
3 stages in processing nutrients
1) Digestion, absorption, and transport to tissues
2)Cellular processing (in cytoplasm)
■ Synthesis of lipids, proteins, and glycogen, or
■ Catabolism (glycolysis) into pyruvic acid and acetyl CoA
3) Oxidative (mitochondrial) breakdown of intermediates into CO2, water, and ATP
Cellular respiration
■ Goal= trap chemical energy in ATP
-Energy also stored in glycogen and fats
-Oxidation of food for fuel
-Step by step removal of pairs of hydrogen atoms (and electron pairs) from substrates à only CO2 left
■ Includes glycolysis, Krebs cycle, oxidative phosphorylation
Oxidation
Gain of oxygen or loss of hydrogen atoms
Oxidation-reduction (redox) reactions
■ Oxidized substances lose electrons and energy
■ Reduced substances gain electrons and energy
■ Catalyzed by enzymes
Dehydrogenases
Removal of hydrogen atoms
Oxidases
Transfer of oxygen
Oxidation-reduction (redox) reactions usually require the help of…
vitamin B derivatives
■ Coenzymes act as hydrogen (or electron) acceptors
■ Nicotinamide adenine dinucleotide (NAD+)
■ Flavin adenine dinucleotide (FAD)
NAD (coenzyme)
■ Nicotinamide adenine dinucleotide (NAD+, Oxidized form)
■ A derivative of vitamin B3 niacin
■ Is reduced to NADH + H+
■ NADH is the reduced containing form
FAD (coenzyme)
■ Flavin adenine dinucleotide (FAD+, Oxidized form)
■ A derivative of vitamin B2 riboflavin
■ Is reduced to FADH2 + H+
■ FADH2 is the energy containing form
■ Both accept hydrogen atoms from TCA cycle:
■ gaining 2 electrons
Metabolic pathway
These are a series of steps in the synthesis or breakdown of a molecule
Allosteric regulation of enzymes
■ Is the regulation of an enzyme by the binding of a substance at a site other than the active site
■ This substance is called an allosteric regulator
■ Phosphofructokinase is an enzyme important early in the glycolysis pathway which leads to the eventual build up of ATP
■ It is inhibited by ATP build up
■ It is stimulated by ADP build up
2 mechanism of ATP synthesis
1) Substrate-level phosphorylation
2) Oxidative phosphorylation
Substrate-level phosphorylation
■ High-energy phosphate groups directly transferred from phosphorylated substrates to ADP
■ Occurs twice in glycolysis and once in Krebs cycle
Oxidative phosphorylation
■ More complex; produces most ATP
■ Chemiosmotic process
■ Couples movement of substances across membrane to chemical reactions
■ Energy used to pump H+ across inner mitochondrial membrane à
■ As flows back through ATP synthase membrane channel ➡️energy used to phosphorylate ADP
Carb metabolism
Oxidation of glucose
■ C6H12O6 + 6O2 à 6H2O + 6CO2 + 32 ATP + heat
■ Glucose enters cells by facilitated diffusion
■ Phosphorylated to glucose-6-phosphate
■ Most cells lack enzymes for reverse reaction à traps glucose inside cell
■ Cells in intestine, kidney, liver can reverse reaction and release glucose
■ Keeps intracellular glucose concentration low à continued glucose entry
Complete glucose catabolism requires these 3 pathways
■ Glycolysis
■ Krebs cycle
■ Electron transport chain and oxidative phosphorylation
Glycolysis
■ 10-step pathway
■ Anaerobic; occurs despite presence/absence of O2
■ Occurs in cytosol
■ Glucose ® 2 pyruvic acid molecules
3 major phases of glycolysis
1) Sugar activation
2) Sugar cleavage
3) Sugar oxidation and ATP formation
Sugar activation
■ Glucose phosphorylated by 2 ATP alpha fructose-1,6-bisphosphate
■ Energy investment phase
-provides activation energy for later reactions
Sugar cleavage
■ Fructose-1,6-bisphosphate à two 3-carbon fragments; isomers
■ Dihydroxyacetone phosphate
■ Quickly reverses to glyceraldehyde 3-phosphate
■ Glyceraldehyde-3-phosphate
Sugar oxidation and ATP formation
■ Six steps; two major events
■ Two 3-carbon fragments oxidized (reducing NAD+)
■ Inorganic phosphate groups (Pi) attached to each oxidized fragment
■ Phosphate group cleavage ➡️4 ATP formed by substrate-level Phosphorylation
Final product of glycolysis
■ 2 pyruvic acid (C3H4O3)
■ 2 NADH + H+ (reduced NAD+)
■ Net gain of 2 ATP (2 used in sugar activation)
For glycolysis to continue…
NAD+ must be present to accept hydrogen atoms
Glycolysis: supply of NAD+ limited
■ NADH must donate its accepted hydrogen atoms to become NAD+ again ➡️glycolysis to continue
■ If oxygen present, occurs in mitochondria during electron transport chain
■ If no oxygen present NADH gives hydrogen atoms back to pyruvic acid, educing it à lactic acid
Glycolysis: fate of lactic acid
■ Most leaves cell à liver
■ May convert glucose-6-phosphate for storage as glycogen or de-phosphorylate and release glucose to blood
Krebs cycle (citric acid cycle)
-Occurs in mitochondrial matrix if oxygen is present
-Fueled by pyruvic acid and fatty acids
-does not directly use O2
-NADH molecules must be oxidized in electron transport chain for Krebs cycle to continue
Krebs cycle: transition phase converts pyruvic acid to acetyl coa in 3 steps:
-Decarboxylation - removal of 1 C to produce acetic acid and CO2
-Oxidation – H atoms removed from acetic acid; picked up by NAD+ à NADH + H+
-Formation of acetyl CoA - Acetic acid + coenzyme A à acetyl coenzyme A (acetyl CoA)
Coenzyme A (CoA): Krebs cycle
■ Derived from pantothenic acid (vitamin B5)
■ This is a very important substance involved in many metabolic pathways:
■ Critical for preparing private to enter the TCA cycle
■ Important in the breakdown of fatty acids for energy
■ Necessary for recycling acetylcholine in the synapse
Products of each turn of Krebs cycle (yield for 1 acetyl CoA)
3 NADH + H+, 1 FADH2, 2 CO2, 1 ATP
Electron transport chain and oxidative phosphorylation
-NADH + H+ and FADH2 (from glycolysis and Krebs cycle) deliver hydrogen atoms
-Hydrogen atoms combined with O2 à water
-Released energy harnessed à ATP by oxidative phosphorylation
-directly uses oxygen
-Pumped H+ creates electrochemical proton gradient
-Created pH gradient; voltage across membrane
-H+ attracted to matrix side of membrane by pH gradient and voltage
Cyanide
■ Binds at the oxygen cite on the last cytochrome
■ Blocks the ETS activity
■ No ETS activity no ATP no good
Chemiosmosis and (OP)
■ Last step (Phase 2) is chemiosmosis)
■ where H+ diffuses back to matrix via ATP synthase à electrical current
■ ATP synthase uses electrical current à ATP
ATP production-summary
■ For 1 glucose molecule processed, cell gains 36 molecules of ATP:
■ 2 from glycolysis
■ 3 from NADH generated in glycolysis
■ 2 from Krebs cycle (through GTP)
■ 23 from ETS
Allosteric regulation of enzymes
-regulation of an enzyme by the binding of a substance (allosteric regulator) at a site other than the active site
Glycolysis
“Anaerobic metabolism”
“Cellular respiration”
-breaks down glucose in cytosol into smaller molecules used by mitochondria
-does not require O2
Starts 1glucose and ends with 2pyruvate, 2ATP
If O2 supplies are adequate
Aerobic reaction
-mitochondria absorbs and breaks down pyruvic acid
-30ATP (cellular respiration)
Oxidative phosphorylation
■ More complex; produces most ATP
■ Chemiosmotic process
■ Couples movement of substances across membrane to chemical reactions
■ Energy used to pump H+ across inner mitochondrial membrane ➡️
■ As flows back through ATP synthase membrane channel ➡️energy used to phosphorylate ADP
Krebs cycle ATP result
2ATP
Lactic acid
When O2 is not present, and pyruvic acid cannot go into mitochondria so it gets converted back to lactic acid which goes into blood➡️glucose in liver (gluconeogenesis)
Gluconeogenesis
Glucose produced from noncarb precursors in the liver when ⬇️glucose
➕by glucagon
Glycogenesis
Glucose➡️glycogen
➕by insulin
Glycogenolysis
Glycogen➡️glucose
➕by glucagon
Beta oxidation
Breakdown fatty acids into acetly-COA➡️krebs cycle
➕by epi and cortisol(need to breakdown fats for energy)
➖by insulin(builds up fats)
LDL
Bad cholesterol
Cholesterol transporters
⬆️cholesterol
HDL
Cholesterol scavengers
⬇️cholesterol
Ammonia
Ammonia is a waste product in the body that is produced when the intestines break down protein from food.
Ammonia➡️urea (excreted in urine)
Transamination
a chemical reaction that moves an amino group from an amino acid to a keto acid, creating new amino acids and keto acids
Deamination
a process that removes an amino group from a molecule, converting it to ammonia
Lipogenesis➕ by
Insulin
Absorbative state
⬆️glucose
Insulin need
Postabsorbative state
⬇️glucose
Coordinated by:
-glucagon
-epi
-glucocorticoids
-GH
