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
